大气颗粒污染物对大鼠膀胱功能的影响及其作用机制的实验研究
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摘要
目的：
拟通过咽后壁滴注大气颗粒污染物制作大鼠柴油机尾气颗粒物(diesel exhaustparticles, DEPs)暴露模型，研究DEPs对膀胱组织毒性作用的剂量-效应、时间-效应关系及机制；检测DEPs暴露环境下膀胱组织中缝隙连接蛋白(Connexin, Cx)家族基因的表达，从转录及翻译水平阐述Cx43与DEPs暴露的关系及其生物学意义；观测缝隙连接介导的细胞间通讯（Gap junction intercellular communication, GJIC）与DEPs暴露的关系，为临床上采用阻断细胞间兴奋传递来治疗DEPs暴露引起的膀胱功能障碍提供理论依据。
方法：
1.采用咽后壁滴注法建立SD大鼠DEPs暴露模型，80只大鼠随机分配于1月和3月不同浓度染毒组(正常组、低剂量染毒组、中剂量染毒组、高剂量染毒组和超高剂量染毒组，即A-E组)，每组各8只。观察膀胱上皮形态的变化，测定膀胱组织抗氧化酶活性和脂质过氧化物水平的改变。
2.采用RT-PCR方法检测膀胱组织中Cx家族基因的表达，Q-PCR和Western blotting方法检测膀胱平滑肌Cx43的表达。
3.体外培养3月超高剂量染毒组原代膀胱平滑肌细胞，应用激光扫描共聚焦显微镜(LSCM)结合荧光光漂白恢复技术(FRAP)，动态研究膀胱平滑肌细胞间缝隙连接介导的细胞间通讯(GJIC)的功能变化及观测缝隙连接阻滞剂18β-GA对GJIC的影响。
结果：
1．采用咽后壁滴注染毒法建立的大鼠DEPs暴露模型方法简单，易操作，可重复性好。
2．3月超高剂量DEPs暴露后，TEM观察发现膀胱上皮细胞间有硝酸镧颗粒物沉积；过碘酸-希夫染色(PAS)染色同样观察到膀胱上皮层表面PAS+层的连续、均一性中断，GAGs(Sulfated Glycosaminoglycan, GAGs)层完整性缺失，部分膀胱上皮细胞脱落。
3．在3月染毒组的高剂量和超高剂量DEPs作用下，膀胱组织内SOD，CAT，GPx和GSH水平出现明显降低，而TBARS则显著性增高。CAT活性的变化出现染毒剂量依赖性改变。
4．Cx26、Cx32、Cx37、Cx40、Cx43和Cx45mRNA在DEPs暴露组及正常组膀胱平滑肌中均有表达，但缺乏Cx36mRNA。3月暴露组中的超高剂量染毒组中Cx40mRNA和Cx43mRNA表达均比正常对照组明显增加，分别增加3.2和2.9倍(p<0.05)，而其它Cx基因表达无显著性差异；Cx43蛋白在3月21.02μg/μl浓度暴露组及正常组膀胱平滑肌中均有表达，且前者中的表达明显高于后者，约增高2.4倍(p<0.05)。
5．胶原酶消化法进行的大鼠膀胱平滑肌细胞原代培养，周期短，获得的平滑肌细胞纯度高。荧光标记染色平滑肌细胞呈单层贴壁生长。LSCM结合FRAP对平滑肌细胞间兴奋传递的功能变化研究发现，在3月21.02μg/μl浓度暴露组中，经瞬间漂白后细胞内荧光强度明显变弱，随着时间的推移，荧光强度明显恢复，而正常对照组，在相同的时间内，漂白细胞荧光恢复不明显。
6．采用缝隙连接阻滞剂18β-GA对3月21.02μg/μl浓度暴露组平滑肌细胞GJIC功能的影响研究发现：18β-GA能明显降低平滑肌细胞间的荧光恢复率，呈浓度依赖相关性，与作用时间无明显关系。
结论：
1. DEPs是一种全身性毒物，对膀胱组织也有一定的毒效应。ROS等自由基引起的氧化损伤可能是DEPs对膀胱产生毒作用的机制之一
2.高浓度DEPs暴露下，膀胱组织可能通过调节Cx基因和蛋白表达以适应环境变化，机制可能与DEPs导致膀胱上皮细胞间隙增宽、膀胱组织内环境氧化还原系统失衡密切相关，但尚需进一步研究证实。
3.缝隙连接是平滑肌细胞间兴奋传递的重要结构基础；本研究采用FRAP技术从功能上证明3月21.02μg/μl浓度暴露组平滑肌GJIC功能增强；3月超高剂量DEPs暴露组平滑肌细胞GJIC功能增强可能是DEPs对膀胱毒性作用的病理机制之一
4.18β-GA作为细胞间缝隙连接阻滞剂，具有阻断膀胱平滑肌细胞间兴奋传递的作用，为改善大气颗粒污染物引起的膀胱功能障碍提供新的概念。
Objective:
Establish of a rat model by aspiration of particles from the pharynx, to determine whetherdiesel exhaust particles (DEPs) could be a toxic agent to the bladder.
Methods:
Rats were randomly assigned into two time groups of forty each group, one month andthree-month exposure group. Then each group was randomly divided into five groups ofdifferent concentrations namely the control group, low dose, medium dose, high dose,and super-high dose exposure groups (group A-E), eight rats respectively. The fourexposure groups were respectively given a volume of30μl SRM1649a suspension at0.28(B),1.58(C),5.61(D),21.03(E) μg/μl，the control group was inoculated with30μlPBS on pharynx posterior wall by sample pipettor beginning at day one when rats wereacclimatized for one week, then repeated per triduum for a total of10or30times in onemonth or three-month exposure group. Three days after the last exposure, rats weredeprived of food for24h and then prepared for experimental procedure. When the ratswere sacrificed, morphologic changes of the urothelium were investigated. Theantioxidase activity and the levels of lipid peroxidation in the bladder were assayed; Theexpression of Cx26、Cx32、Cx36、Cx37、Cx40、Cx43and Cx45mRNA in bladder weredetected by RT-PCR techniques, in transcript levels; The levels of Cx43protein inbladder were detected by Western blotting and Q-PCR; Primary cell cultures were set upfrom fragments of rat bladder at super-high dose in three-month group. After cultureddetrusor cells were loaded with the fluorescent dye6-CFDA, the function of GJIC in thecultured bladder detrusor cells were detected by fluorescence redistribution afterphotobleaching (FRAP) techniques; The effect of18β-GA at various concentrations on cultured rat bladder detrusor cells of super-high dose in three-month group were observedby FRAP techniques under laser scanning confocal microscope (LSCM). Meanwhile, theeffect of18β-GA of the same concentrations at various times on cultured rat bladderdetrusor cells of super-high dose in three-month group were also observed by FRAPtechniques in this study.
Results:
1. Rats exposure model established by aspiration of particles from the pharynx is simple,easy to operate and good repeatability.
2. In the three-month group, DEPs at doses of21.03μg/μl insulted the structuralintegrity of surface glycosaminoglycans, widened the gap between urothelial cells,increased levels of lipid peroxidation, and decreased antioxidase activities in theurinary bladder (p<0.05). Furthermore, DEPs at doses of5.61μg/μl decreasedglutathione, catalase, and glutathione peroxidase activities (p<0.05).
3. RT-PCR analysis of control and exposure group rat bladder RNA demonstrated thepresence of a transcript for six connexins (Cx26, Cx32, Cx37, Cx40, Cx43, and Cx45but not for Cx36), the levels of Cx43, Cx40mRNA in doses of21.03μg/μl ofthree-month group was higher than in the control groups, increased2.9and3.2timesrespectively (p<0.05). But, the rest Cx mRNA expression were no significantdifferences (p<0.05). The level of Cx43protein expression in detrusor tissue of thesuper-high dose in three-month group was notably higher than in the control group,increased2.4times (p<0.05).
4. By collagenase digestion of rat bladder detrusor cells in primary culture, the cycle isshort, and high purity detrusor cells can be obtained. Cultured detrusor cells loadedwith6-CFDA fluorescence probes grew to a flattened simple form. The functions ofGJIC in the cultured rat bladder detrusor cells of the super-high dose in three-monthgroup and control groups were detected by FRAP techniques. It shows that thefluorescence intensity was gradually recovered at different times after bleaching inthe super-high dose in three-month group. The mean fluorescence recovery rates in doses of21.03μg/μl of three-month group (4minutes) were (36.4±0.73)%. In contrastto the super-high dose in three-month group, the fluorescence recovery of thebleached cells in the control groups were not obvious in the same time. The meanfluorescence recovery rates of the control groups (4minutes) were (11.4±0.94)%.
5. The effect of18β-GA at various concentrations on cultured rat bladder detrusor cellsof super-high dose in three-month group were observed by FRAP techniques. Theseresults showed that no time-dependent in the functional change of GJIC at super-highdose in three-month group cells.
Conclusion:
1. These results led to the conclusion that DEPs were a toxic agent in the bladder. Thetoxic effects might be attributed to oxidative damage mediated by pro-oxidant/antioxidant imbalance or excessive free radicals.
2. Exposed to high concentrations of DEPs, bladder tissue may regulate the Cx gene andprotein expression to adapt to environmental changes. The mechanism may be haverelationship with DEPs lead to bladder epithelial cell gap widened and imblance ofthe environmental redox system in the bladder tissue, but further studies are needed toconfirm.
3. The gap junction is an important structural basis for detrusor excitation transmissionbetween adjacent cells. It has demonstrated from a functional perspective thatdetrusor GJIC enhancement in dose of21.03μg/μl of three-month group by FRAPtechnique. One of the pathological mechanisms leading to bladder toxic effects byDEPs may be is GJIC enhancements between detrusor cells.
4. At cell levels, the GJIC of super-high dose in three-month group was inhibited by18β-glycyrrhetinic acid (18β-GA), as a gap junction blocker. These results maycontribute to new concepts in the treatment of bladder disease caused by DEPs in thefuture.
拟通过咽后壁滴注大气颗粒污染物制作大鼠柴油机尾气颗粒物(diesel exhaustparticles, DEPs)暴露模型，研究DEPs对膀胱组织毒性作用的剂量-效应、时间-效应关系及机制；检测DEPs暴露环境下膀胱组织中缝隙连接蛋白(Connexin, Cx)家族基因的表达，从转录及翻译水平阐述Cx43与DEPs暴露的关系及其生物学意义；观测缝隙连接介导的细胞间通讯（Gap junction intercellular communication, GJIC）与DEPs暴露的关系，为临床上采用阻断细胞间兴奋传递来治疗DEPs暴露引起的膀胱功能障碍提供理论依据。
方法：
1.采用咽后壁滴注法建立SD大鼠DEPs暴露模型，80只大鼠随机分配于1月和3月不同浓度染毒组(正常组、低剂量染毒组、中剂量染毒组、高剂量染毒组和超高剂量染毒组，即A-E组)，每组各8只。观察膀胱上皮形态的变化，测定膀胱组织抗氧化酶活性和脂质过氧化物水平的改变。
2.采用RT-PCR方法检测膀胱组织中Cx家族基因的表达，Q-PCR和Western blotting方法检测膀胱平滑肌Cx43的表达。
3.体外培养3月超高剂量染毒组原代膀胱平滑肌细胞，应用激光扫描共聚焦显微镜(LSCM)结合荧光光漂白恢复技术(FRAP)，动态研究膀胱平滑肌细胞间缝隙连接介导的细胞间通讯(GJIC)的功能变化及观测缝隙连接阻滞剂18β-GA对GJIC的影响。
结果：
1．采用咽后壁滴注染毒法建立的大鼠DEPs暴露模型方法简单，易操作，可重复性好。
2．3月超高剂量DEPs暴露后，TEM观察发现膀胱上皮细胞间有硝酸镧颗粒物沉积；过碘酸-希夫染色(PAS)染色同样观察到膀胱上皮层表面PAS+层的连续、均一性中断，GAGs(Sulfated Glycosaminoglycan, GAGs)层完整性缺失，部分膀胱上皮细胞脱落。
3．在3月染毒组的高剂量和超高剂量DEPs作用下，膀胱组织内SOD，CAT，GPx和GSH水平出现明显降低，而TBARS则显著性增高。CAT活性的变化出现染毒剂量依赖性改变。
4．Cx26、Cx32、Cx37、Cx40、Cx43和Cx45mRNA在DEPs暴露组及正常组膀胱平滑肌中均有表达，但缺乏Cx36mRNA。3月暴露组中的超高剂量染毒组中Cx40mRNA和Cx43mRNA表达均比正常对照组明显增加，分别增加3.2和2.9倍(p<0.05)，而其它Cx基因表达无显著性差异；Cx43蛋白在3月21.02μg/μl浓度暴露组及正常组膀胱平滑肌中均有表达，且前者中的表达明显高于后者，约增高2.4倍(p<0.05)。
5．胶原酶消化法进行的大鼠膀胱平滑肌细胞原代培养，周期短，获得的平滑肌细胞纯度高。荧光标记染色平滑肌细胞呈单层贴壁生长。LSCM结合FRAP对平滑肌细胞间兴奋传递的功能变化研究发现，在3月21.02μg/μl浓度暴露组中，经瞬间漂白后细胞内荧光强度明显变弱，随着时间的推移，荧光强度明显恢复，而正常对照组，在相同的时间内，漂白细胞荧光恢复不明显。
6．采用缝隙连接阻滞剂18β-GA对3月21.02μg/μl浓度暴露组平滑肌细胞GJIC功能的影响研究发现：18β-GA能明显降低平滑肌细胞间的荧光恢复率，呈浓度依赖相关性，与作用时间无明显关系。
结论：
1. DEPs是一种全身性毒物，对膀胱组织也有一定的毒效应。ROS等自由基引起的氧化损伤可能是DEPs对膀胱产生毒作用的机制之一
2.高浓度DEPs暴露下，膀胱组织可能通过调节Cx基因和蛋白表达以适应环境变化，机制可能与DEPs导致膀胱上皮细胞间隙增宽、膀胱组织内环境氧化还原系统失衡密切相关，但尚需进一步研究证实。
3.缝隙连接是平滑肌细胞间兴奋传递的重要结构基础；本研究采用FRAP技术从功能上证明3月21.02μg/μl浓度暴露组平滑肌GJIC功能增强；3月超高剂量DEPs暴露组平滑肌细胞GJIC功能增强可能是DEPs对膀胱毒性作用的病理机制之一
4.18β-GA作为细胞间缝隙连接阻滞剂，具有阻断膀胱平滑肌细胞间兴奋传递的作用，为改善大气颗粒污染物引起的膀胱功能障碍提供新的概念。
Objective:
Establish of a rat model by aspiration of particles from the pharynx, to determine whetherdiesel exhaust particles (DEPs) could be a toxic agent to the bladder.
Methods:
Rats were randomly assigned into two time groups of forty each group, one month andthree-month exposure group. Then each group was randomly divided into five groups ofdifferent concentrations namely the control group, low dose, medium dose, high dose,and super-high dose exposure groups (group A-E), eight rats respectively. The fourexposure groups were respectively given a volume of30μl SRM1649a suspension at0.28(B),1.58(C),5.61(D),21.03(E) μg/μl，the control group was inoculated with30μlPBS on pharynx posterior wall by sample pipettor beginning at day one when rats wereacclimatized for one week, then repeated per triduum for a total of10or30times in onemonth or three-month exposure group. Three days after the last exposure, rats weredeprived of food for24h and then prepared for experimental procedure. When the ratswere sacrificed, morphologic changes of the urothelium were investigated. Theantioxidase activity and the levels of lipid peroxidation in the bladder were assayed; Theexpression of Cx26、Cx32、Cx36、Cx37、Cx40、Cx43and Cx45mRNA in bladder weredetected by RT-PCR techniques, in transcript levels; The levels of Cx43protein inbladder were detected by Western blotting and Q-PCR; Primary cell cultures were set upfrom fragments of rat bladder at super-high dose in three-month group. After cultureddetrusor cells were loaded with the fluorescent dye6-CFDA, the function of GJIC in thecultured bladder detrusor cells were detected by fluorescence redistribution afterphotobleaching (FRAP) techniques; The effect of18β-GA at various concentrations on cultured rat bladder detrusor cells of super-high dose in three-month group were observedby FRAP techniques under laser scanning confocal microscope (LSCM). Meanwhile, theeffect of18β-GA of the same concentrations at various times on cultured rat bladderdetrusor cells of super-high dose in three-month group were also observed by FRAPtechniques in this study.
Results:
1. Rats exposure model established by aspiration of particles from the pharynx is simple,easy to operate and good repeatability.
2. In the three-month group, DEPs at doses of21.03μg/μl insulted the structuralintegrity of surface glycosaminoglycans, widened the gap between urothelial cells,increased levels of lipid peroxidation, and decreased antioxidase activities in theurinary bladder (p<0.05). Furthermore, DEPs at doses of5.61μg/μl decreasedglutathione, catalase, and glutathione peroxidase activities (p<0.05).
3. RT-PCR analysis of control and exposure group rat bladder RNA demonstrated thepresence of a transcript for six connexins (Cx26, Cx32, Cx37, Cx40, Cx43, and Cx45but not for Cx36), the levels of Cx43, Cx40mRNA in doses of21.03μg/μl ofthree-month group was higher than in the control groups, increased2.9and3.2timesrespectively (p<0.05). But, the rest Cx mRNA expression were no significantdifferences (p<0.05). The level of Cx43protein expression in detrusor tissue of thesuper-high dose in three-month group was notably higher than in the control group,increased2.4times (p<0.05).
4. By collagenase digestion of rat bladder detrusor cells in primary culture, the cycle isshort, and high purity detrusor cells can be obtained. Cultured detrusor cells loadedwith6-CFDA fluorescence probes grew to a flattened simple form. The functions ofGJIC in the cultured rat bladder detrusor cells of the super-high dose in three-monthgroup and control groups were detected by FRAP techniques. It shows that thefluorescence intensity was gradually recovered at different times after bleaching inthe super-high dose in three-month group. The mean fluorescence recovery rates in doses of21.03μg/μl of three-month group (4minutes) were (36.4±0.73)%. In contrastto the super-high dose in three-month group, the fluorescence recovery of thebleached cells in the control groups were not obvious in the same time. The meanfluorescence recovery rates of the control groups (4minutes) were (11.4±0.94)%.
5. The effect of18β-GA at various concentrations on cultured rat bladder detrusor cellsof super-high dose in three-month group were observed by FRAP techniques. Theseresults showed that no time-dependent in the functional change of GJIC at super-highdose in three-month group cells.
Conclusion:
1. These results led to the conclusion that DEPs were a toxic agent in the bladder. Thetoxic effects might be attributed to oxidative damage mediated by pro-oxidant/antioxidant imbalance or excessive free radicals.
2. Exposed to high concentrations of DEPs, bladder tissue may regulate the Cx gene andprotein expression to adapt to environmental changes. The mechanism may be haverelationship with DEPs lead to bladder epithelial cell gap widened and imblance ofthe environmental redox system in the bladder tissue, but further studies are needed toconfirm.
3. The gap junction is an important structural basis for detrusor excitation transmissionbetween adjacent cells. It has demonstrated from a functional perspective thatdetrusor GJIC enhancement in dose of21.03μg/μl of three-month group by FRAPtechnique. One of the pathological mechanisms leading to bladder toxic effects byDEPs may be is GJIC enhancements between detrusor cells.
4. At cell levels, the GJIC of super-high dose in three-month group was inhibited by18β-glycyrrhetinic acid (18β-GA), as a gap junction blocker. These results maycontribute to new concepts in the treatment of bladder disease caused by DEPs in thefuture.
引文
1. China: the air pollution capital of the world. Lancet.2005;366(9499):1761-2.
2.阚海东,黄薇,陈秉衡.中国城市大气污染和健康影响研究的回顾和展望.第四届国家环境与健康论坛论文集.2009.
3. van DA, Martin RV, Brauer M, et al. Global estimates of ambient fine particulatematter concentrations from satellite-based aerosol optical depth: development andapplication. Environ Health Perspect.2010;118(6):847-55.
4. Terzano C, Di SF, Conti V, Graziani E, Petroianni A. Air pollution ultrafineparticles: toxicity beyond the lung. Eur Rev Med Pharmacol Sci.2010;14(10):809-21.
5. Castranova V, Ma JY, Yang HM, et al. Effect of exposure to diesel exhaustparticles on the susceptibility of the lung to infection. Environ Health Perspect.2001;109Suppl4(609-12.
6. Ghio AJ, Smith CB, Madden MC. Diesel exhaust particles and airwayinflammation. Curr Opin Pulm Med.2012;18(2):144-50.
7. Lee GB, Brandt EB, Xiao C, et al. Diesel exhaust particles induce cysteineoxidation and s-glutathionylation in house dust mite induced murine asthma.PLOS ONE.2013;8(3):e60632.
8. Fortoul TI, Rodriguez-Lara V, Gonzalez-Villalva A, et al. Vanadium inhalation ina mouse model for the understanding of air-suspended particle systemicrepercussion. J Biomed Biotechnol.2011;2011(951043.
9.杨学礼,黄建凤.大气颗粒物污染对心血管系统的影响及其机制研究进展.中华预防医学杂志.2011;45(8):749-751.
10. Michael S, Montag M, Dott W. Pro-inflammatory effects and oxidative stress inlung macrophages and epithelial cells induced by ambient particulatematter.LID-S0269-7491(13)00041-9[pii]LID-10.1016/j.envpol.2013.01.026[doi]. Environ Pollut.2013;
11. Larsson N, Brown J, Stenfors N, et al. Airway inflammatory responses to dieselexhaust in allergic rhinitics. Inhal Toxicol.2013;25(3):160-7.
12. Salvi SS, Nordenhall C, Blomberg A, et al. Acute exposure to diesel exhaustincreases IL-8and GRO-alpha production in healthy human airways. Am J RespirCrit Care Med.2000;161(2Pt1):550-7.
13. Ku SK, Bae JS. Concentration dependent anti-inflammatory effects thrombin onpolyphosphate-mediated inflammatory responses in vitro and in vivo. InflammRes.2013;
14. Manna SK, Sarkar S, Barr J, et al. Single-walled carbon nanotube inducesoxidative stress and activates nuclear transcription factor-kappaB in humankeratinocytes. Nano Lett.2005;5(9):1676-84.
15.李凤菊,邵龙义,杨书申.大气颗粒物中重金属的化学特征和来源分析.中原工学院学报.2007;01):7-11.
16. Timblin C, BeruBe K, Churg A, et al. Ambient particulate matter causes activationof the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis inlung epithelial cells. Cancer Res.1998;58(20):4543-7.
17. Khatlani TS, Wislez M, Sun M, et al. c-Jun N-terminal kinase is activated innon-small-cell lung cancer and promotes neoplastic transformation in humanbronchial epithelial cells. Oncogene.2007;26(18):2658-66.
18. He X, Son SY, James K, et al. Exploring a novel ultrafine particle counter forutilization in respiratory protection studies. J Occup Environ Hyg.2013;10(4):D52-4.
19. Churg A, Gilks B, Dai J. Induction of fibrogenic mediators by fine and ultrafinetitanium dioxide in rat tracheal explants. Am J Physiol.1999;277(5Pt1):L975-82.
20.原福胜,马亚萍,赵五红,郭风华.大气颗粒物对人双核淋巴细胞微核率的影响.环境与健康杂志.2005;22(4):277-278.
21. De Flora S. Threshold mechanisms and site specificity in chromium(VI)carcinogenesis. Carcinogenesis.2000;21(4):533-41.
22. Hartwig A. Metal interaction with redox regulation: an integrating concept inmetal carcinogenesis. Free Radic Biol Med.2013;55(63-72.
23. Shields PG, Bowman ED, Harrington AM, Doan VT, Weston A. Polycyclicaromatic hydrocarbon-DNA adducts in human lung and cancer susceptibilitygenes. Cancer Res.1993;53(15):3486-92.
24. Georgiadis P, Kovacs K, Kaila S, et al. Development and validation of a directsandwich chemiluminescence immunoassay for measuring DNA adducts ofbenzo[a]pyrene and other polycyclic aromatic hydrocarbons. Mutagenesis.2012;27(5):589-97.
25.王驭良,许克新,胡浩等.北京地区成年女性膀胱过度活动症流行病学调查及对患者生活质量的影响.中华泌尿外科杂志.2010;8):550-554.
26. Palmer MH, Hardin SR, Behrend C, Collins SK, Madigan CK, Carlson JR.Urinary incontinence and overactive bladder in patients with heart failure. J Urol.2009;182(1):196-202.
27.杨为民,袁晓奕.膀胱过度活动症的诊断与治疗进展.临床泌尿外科杂志.2011;26(1):1-3.
28. Zhang ZB, Zhou DR, Song B. Gap junctional protein connexin43in rat detrusormuscle with unstable bladder. Chin Med J (Engl).2008;121(17):1698-701.
29. Onoue S, Yamamoto N, Seto Y, Yamada S. Pharmacokinetic study of nicotine andits metabolite cotinine to clarify possible association between smoking andvoiding dysfunction in rats using UPLC/ESI-MS. Drug Metab Pharmacokinet.2011;26(4):416-22.
30. Azadzoi KM, Yalla SV, Siroky MB. Oxidative stress and neurodegeneration in theischemic overactive bladder. J Urol.2007;178(2):710-5.
31. Terzano C, Di SF, Conti V, Graziani E, Petroianni A. Air pollution ultrafineparticles: toxicity beyond the lung. Eur Rev Med Pharmacol Sci.2010;14(10):809-21.
32. Sun Q, Yue P, Kirk RI, et al. Ambient air particulate matter exposure and tissuefactor expression in atherosclerosis. Inhal Toxicol.2008;20(2):127-37.
33. Brook RD, Franklin B, Cascio W, et al. Air pollution and cardiovascular disease: astatement for healthcare professionals from the Expert Panel on Population andPrevention Science of the American Heart Association. Circulation.2004;109(21):2655-71.
34. Castranova V, Ma JY, Yang HM, et al. Effect of exposure to diesel exhaustparticles on the susceptibility of the lung to infection. Environ Health Perspect.2001;109Suppl4(609-12.
35. Rao GV, Tinkle S, Weissman DN, et al. Efficacy of a technique for exposing themouse lung to particles aspirated from the pharynx. J Toxicol Environ Health A.2003;66(15):1441-52.
36. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxidedismutase. Clin Chem.1988;34(3):497-500.
37. Wendel A. Glutathione peroxidase. In: Methods Enzymol.1981, p.325-333.
38. Claiborne A. Catalase activity. In: CRC Handbook of Methods for OxygenRadical Research. Florida: Boca Raton;1985, p.283–284.
39. Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzene-induced livernecrosis. Protective role of glutathione and evidence for3,4-bromobenzeneoxide as the hepatotoxic metabolite. Pharmacology.1974;11(3):151-69.
40. Wasowicz W, Neve J, Peretz A. Optimized steps in fluorometric determination ofthiobarbituric acid-reactive substances in serum: importance of extraction pH andinfluence of sample preservation and storage. Clin Chem.1993;39(12):2522-6.
41. Lora L, Mazzon E, Martines D, et al. Hepatocyte tight-junctional permeability isincreased in rat experimental colitis. Gastroenterology.1997;113(4):1347-54.
42. Scheepe JR, de Jong BW, Wolffenbuttel KP, Arentshorst ME, Lodder P, Kok DJ.The effect of oxybutynin on structural changes of the obstructed guinea pigbladder. J Urol.2007;178(4Pt2):1807-12.
43.张文丽，崔九思，徐东群.大气中细颗粒物的污染特征及其生物效应.中国环境卫生..2003;6(1):90-102.
44.张文丽,崔九思,徐东群,戚其平.大气中细颗粒物的污染特征及其生物效应.中国环境卫生.2003;6(3):90-102.
45. Terzano C, Di SF, Conti V, Graziani E, Petroianni A. Air pollution ultrafineparticles: toxicity beyond the lung. Eur Rev Med Pharmacol Sci.2010;14(10):809-21.
46. Fortoul TI, Rodriguez-Lara V, Gonzalez-Villalva A, et al. Vanadium inhalation ina mouse model for the understanding of air-suspended particle systemicrepercussion. J Biomed Biotechnol.2011;2011(951043.
47. Parsons CL, Boychuk D, Jones S, Hurst R, Callahan H. Bladder surfaceglycosaminoglycans: an epithelial permeability barrier. J Urol.1990;143(1):139-42.
48. Cetinel S, Bl C, Ercan F, Hrda C, San T. Indomethacin-induced morphologicchanges in the rat urinary bladder epithelium. Urology.2003;61(1):236-42.
49. Cetinel S, Bl C, Ercan F, Hrda C, San T. Indomethacin-induced morphologicchanges in the rat urinary bladder epithelium. Urology.2003;61(1):236-42.
50. Soler R, Bruschini H, Freire MP, Alves MT, Srougi M, Ortiz V. Urine is necessaryto provoke bladder inflammation in protamine sulfate induced urothelial injury. JUrol.2008;180(4):1527-31.
51. Zeybek A, Saglam B, Cikler E, Cetinel S, Ercan F, Sener G. Protective effects oftaurine on protamine sulfate induced bladder damage. World J Urol.2006;24(4):438-44.
52.孟紫强,张波.二氧化硫吸入对大鼠脑组织细胞的氧化损伤作用.中国环境科学.2001;21(5):464-467.
53. Schlenker EH. An evaluation of ventilation in dystrophic Syrian hamsters. J ApplPhysiol.1984;56(4):914-21.
54. Takenaka S, Karg E, Roth C, et al. Pulmonary and systemic distribution of inhaledultrafine silver particles in rats. Environ Health Perspect.2001;109Suppl4(547-51.
55.孟紫强.二氧化硫吸入对小鼠9种脏器谷胱甘肽过氧化物酶活性的影响.环境与职业医学.2003;20(1):6-9.
56. Afaq F, Abidi P, Rahman Q. N-acetyl L-cysteine attenuates oxidant-mediatedtoxicity induced by chrysotile fibers. Toxicol Lett.2000;117(1-2):53-60.
57.杨春雪,阚海东,陈仁杰.我国大气细颗粒物水平、成分、来源及污染特征.环境与健康杂志.2011;08):735-738+753.
58. Meng Z, Zhang Q. Oxidative damage of dust storm fine particles instillation onlungs, hearts and livers of rats. Environ Toxicol Pharmacol.2006;22(3):277-82.
59. Mossman BT. Introduction to serial reviews on the role of reactive oxygen andnitrogen species (ROS/RNS) in lung injury and diseases. Free Radic Biol Med.2003;34(9):1115-6.
60. Takenaka S, Karg E, Roth C, et al. Pulmonary and systemic distribution of inhaledultrafine silver particles in rats. Environ Health Perspect.2001;109Suppl4(547-51.
61. Creutzenberg O, Bellmann B, Korolewitz R, et al. Change in agglomeration statusand toxicokinetic fate of various nanoparticles in vivo following lung exposure inrats. Inhal Toxicol.2012;24(12):821-30.
62. Dellinger B, Pryor WA, Cueto R, Squadrito GL, Hegde V, Deutsch WA. Role offree radicals in the toxicity of airborne fine particulate matter. Chem Res Toxicol.2001;14(10):1371-7.
63. Robertson S, Gray GA, Duffin R, et al. Diesel exhaust particulate inducespulmonary and systemic inflammation in rats without impairing endothelialfunction ex vivo or in vivo. Part Fibre Toxicol.2012;9(9.
64. Haefliger JA, Tissieres P, Tawadros T, et al. Connexins43and26aredifferentially increased after rat bladder outlet obstruction. Exp Cell Res.2002;274(2):216-25.
65. Fraser SE, Green CR, Bode HR, Gilula NB. Selective disruption of gap junctionalcommunication interferes with a patterning process in hydra. Science.1987;237(4810):49-55.
66. Deans MR, Volgyi B, Goodenough DA, Bloomfield SA, Paul DL. Connexin36isessential for transmission of rod-mediated visual signals in the mammalian retina.Neuron.2002;36(4):703-12.
67. Kelsell DP, Dunlop J, Stevens HP, et al. Connexin26mutations in hereditarynon-syndromic sensorineural deafness. Nature.1997;387(6628):80-3.
68. Abascal F, Zardoya R. Evolutionary analyses of gap junction protein families.Biochim Biophys Acta.2013;1828(1):4-14.
69. Nagaraja S, Kapela A, Tsoukias NM. Intercellular communication in the vascularwall: a modeling perspective. Microcirculation.2012;19(5):391-402.
70. Paul M, Wichter T, Gerss J, et al. Connexin Expression Patterns inArrhythmogenic Right Ventricular Cardiomyopathy.LID-S0002-9149(13)00395-0[pii]LID-10.1016/j.amjcard.2013.01.299[doi]. Am JCardiol.2013;
71. Lubitz SA, Ellinor PT. A common connexion between gap junctions, singlenucleotide polymorphisms, and atrial fibrillation. Can J Cardiol.2013;29(1):3-5.
72.陶霞,张树辉,苏定冯.细胞缝隙连接与心血管疾病.生理科学进展.2001;32(4):371-377.
73. Salameh A, Dhein S. Adrenergic control of cardiac gap junction function andexpression. Naunyn Schmiedebergs Arch Pharmacol.2011;383(4):331-46.
74. Yamanaka I, Kuraoka A, Inai T, Ishibashi T, Shibata Y. Differential expression ofmajor gap junction proteins, connexins26and32, in rat mammary glands duringpregnancy and lactation. Histochem Cell Biol.2001;115(4):277-84.
75. Shibata Y, Kumai M, Nishii K, Nakamura K. Diversity and molecular anatomy ofgap junctions. Med Electron Microsc.2001;34(3):153-9.
76. Kim SJ, Park EY, Hwang TK, Kim JC. Therapeutic effects of connexin inhibitorson detrusor overactivity induced by bladder outlet obstruction in rats. Urology.2011;78(2):475.e1-7.
77. Neuhaus J, Weimann A, Stolzenburg JU, Wolburg H, Horn LC, Dorschner W.Smooth muscle cells from human urinary bladder express connexin43in vivo andin vitro. World J Urol.2002;20(4):250-4.
78. Asamoto M, Takahashi S, Imaida K, Shirai T, Fukushima S. Increased gapjunctional intercellular communication capacity and connexin43and26expression in rat bladder carcinogenesis. Carcinogenesis.1994;15(10):2163-6.
79. Sakai T, Kasahara K, Tomita K, Ikegaki I, Kuriyama H.5-Hydroxytryptamine-induced bladder hyperactivity via the5-HT2A receptor inpartial bladder outlet obstruction in rats. Am J Physiol Renal Physiol.2013;304(7):F1020-7.
80. Sui GP, Coppen SR, Dupont E, et al. Impedance measurements and connexinexpression in human detrusor muscle from stable and unstable bladders. BJU Int.2003;92(3):297-305.
81. Spray DC. Gap junction proteins: where they live and how they die. Circ Res.1998;83(6):679-81.
82. Perez-Armendariz EM, Cruz-Miguel L, Coronel-Cruz C, et al. Connexin36isexpressed in beta and connexins26and32in acinar cells at the end of thesecondary transition of mouse pancreatic development and increase during fetaland perinatal life. Anat Rec (Hoboken).2012;295(6):980-90.
83. Muller-Borer BJ, Cascio WE, Esch GL, Grisham JW, Anderson PA, Malouf NN.Acquired cell-to-cell coupling and "cardiac-like" calcium oscillations in adultstem cells in a cardiomyocyte microenvironment. Conf Proc IEEE Eng Med BiolSoc.2006;1(576-9.
84.孙彧,张丽娉,陈仁华,邹云增,李毅刚.缺氧大鼠乳鼠心肌细胞中sema3a调节connexin43磷酸化水平的相关性研究.国际心血管病杂志.2011;38(5):301-304.
85. Fialova M, Dlugosova K, Okruhlicova L, Kristek F, Manoach M, Tribulova N.Adaptation of the heart to hypertension is associated with maladaptive gapjunction connexin-43remodeling. Physiol Res.2008;57(1):7-11.
86. Jongen WM, Fitzgerald DJ, Asamoto M, et al. Regulation of connexin43-mediated gap junctional intercellular communication by Ca2+in mouseepidermal cells is controlled by E-cadherin. J Cell Biol.1991;114(3):545-55.
87.张卫泽,王方正.心肌细胞缝隙连接及其与心血管疾病和心律失常的关系.中国心脏起搏与心电生理杂志.2002;16(2):146-149.
88. Miyoshi H, Boyle MB, MacKay LB, Garfield RE. Gap junction currents incultured muscle cells from human myometrium. Am J Obstet Gynecol.1998;178(3):588-93.
89. Ciray HN, Guner H, Hakansson H, Tekelioglu M, Roomans GM, Ulmsten U.Morphometric analysis of gap junctions in nonpregnant and term pregnant humanmyometrium. Acta Obstet Gynecol Scand.1995;74(7):497-504.
90. Albrecht JL, Atal NS, Tadros PN, et al. Rat uterine myometrium contains the gapjunction protein connexin45, which has a differing temporal expression patternfrom connexin43. Am J Obstet Gynecol.1996;175(4Pt1):853-8.
91. Kirchhoff S, Kim JS, Hagendorff A, et al. Abnormal cardiac conduction andmorphogenesis in connexin40and connexin43double-deficient mice. Circ Res.2000;87(5):399-405.
92. Kirchhoff S, Kim JS, Hagendorff A, et al. Abnormal cardiac conduction andmorphogenesis in connexin40and connexin43double-deficient mice. Circ Res.2000;87(5):399-405.
93.周逢海.缝隙连接介导的细胞间通讯及其与逼尿肌不稳定关系的实验研究.金锡御,主编.外科学(泌尿外).第三军医大学,2004.
94. Haefliger JA, Castillo E, Waeber G, et al. Hypertension increases connexin43in atissue-specific manner. Circulation.1997;95(4):1007-14.
95. Haefliger JA, Meda P, Formenton A, et al. Aortic connexin43is decreased duringhypertension induced by inhibition of nitric oxide synthase. Arterioscler ThrombVasc Biol.1999;19(7):1615-22.
96. Wang TL, Tseng YZ, Chang H. Regulation of connexin43gene expression bycyclical mechanical stretch in neonatal rat cardiomyocytes. Biochem Biophys ResCommun.2000;267(2):551-7.
97. Lindner P, Mattiasson A, Persson L, Uvelius B. Reversibility of detrusorhypertrophy and hyperplasia after removal of infravesical outflow obstruction inthe rat. J Urol.1988;140(3):642-6.
98. Okada S, Kojima Y, Hamamoto S, Mizuno K, Sasaki S, Kohri K. Dietary soyisoflavone replacement improves detrusor overactivity of ovariectomized ratswith altered connexin-43expression in the urinary bladder. BJU Int.2009;103(10):1429-35.
99. Imamura M, Kanematsu A, Yamamoto S, et al. Basic fibroblast growth factormodulates proliferation and collagen expression in urinary bladder smooth musclecells. Am J Physiol Renal Physiol.2007;293(4):F1007-17.
100.司徒镇强，吴军正.《细胞培养》.北京:世界图书出版公司;
101. Li L, Jiang C, Hao P, Li W, Song C, Song B. Changes of gap junctional cell-cellcommunication in overactive detrusor in rats. Am J Physiol Cell Physiol.2007;293(5):C1627-35.
102.祁琨,邓芙蓉,郭新彪.纳米二氧化钛颗粒对人肺成纤维细胞缝隙连接通讯的影响.北京大学学报（医学版）.2009;41(3):297-301.
103. Reits EA, Neefjes JJ. From fixed to FRAP: measuring protein mobility andactivity in living cells. Nat Cell Biol.2001;3(6):E145-7.
104. Campbell JH, Campbell GR. Smooth muscle phenotypic modulation--a personalexperience. Arterioscler Thromb Vasc Biol.2012;32(8):1784-9.
105. Sui GP, Wu C, Fry CH. The electrophysiological properties of cultured andfreshly isolated detrusor smooth muscle cells. J Urol.2001;165(2):627-32.
106. Harriss DR. Smooth muscle cell culture: a new approach to the study of humandetrusor physiology and pathophysiology. Br J Urol.1995;75Suppl1(18-26.
107. Baskin LS, Howard PS, Duckett JW, Snyder HM, Macarak EJ. Bladder smoothmuscle cells in culture: I. Identification and characterization. J Urol.1993;149(1):190-7.
108. Suson KD, Stec AA, Shimoda LA, Gearhart JP. Initial characterization ofexstrophy bladder smooth muscle cells in culture. J Urol.2012;188(4Suppl):1521-7.
109. Wade MH, Trosko JE, Schindler M. A fluorescence photobleaching assay of gapjunction-mediated communication between human cells. Science.1986;232(4749):525-8.
110. Nagaraja S, Kapela A, Tsoukias NM. Intercellular communication in the vascularwall: a modeling perspective. Microcirculation.2012;19(5):391-402.
111. Wu J, Taylor RN, Sidell N. Retinoic acid regulates gap junction intercellularcommunication in human endometrial stromal cells through modulation of thephosphorylation status of connexin43. J Cell Physiol.2013;228(4):903-10.
112. Hashitani H, Fukuta H, Takano H, Klemm MF, Suzuki H. Origin and propagationof spontaneous excitation in smooth muscle of the guinea-pig urinary bladder. JPhysiol.2001;530(Pt2):273-86.
113. Santicioli P, Maggi CA. Effect of18beta-glycyrrhetinic acid on electromechanicalcoupling in the guinea-pig renal pelvis and ureter. Br J Pharmacol.2000;129(1):163-9.
114. Boedtkjer E, Kim S, Aalkjaer C. Endothelial alkalinisation inhibits gap junctioncommunication and endothelium-derived hyperpolarisations in mouse mesentericarteries. J Physiol.2013;591(Pt6):1447-61.
115. Guan BC, Si JQ, Jiang ZG. Blockade of gap junction coupling by glycyrrhetinicacids in guinea pig cochlear artery: a whole-cell voltage-and current-clampstudy. Br J Pharmacol.2007;151(7):1049-60.
116. Krutovskikh VA, Piccoli C, Yamasaki H. Gap junction intercellularcommunication propagates cell death in cancerous cells. Oncogene.2002;21(13):1989-99.
1. Jiang JX, Gu S. Gap junction-and hemichannel-independent actions of connexins.Biochim Biophys Acta.2005;1711(2):208-14.
2. Nagaraja S, Kapela A, Tsoukias NM. Intercellular communication in the vascularwall: a modeling perspective. Microcirculation.2012;19(5):391-402.
3. Morris CL. Urge urinary incontinence and the brain factor.LID-10.1002/nau.22357[doi]. Neurourol Urodyn.2012;
4. Andersson KE. Detrusor myocyte activity and afferent signaling. NeurourolUrodyn.2010;29(1):97-106.
5. Miyazato M, Sugaya K, Nishijima S, et al. Changes of bladder activity andconnexin43-derived gap junctions after partial bladder-outlet obstruction in rats.Int Urol Nephrol.2009;41(4):815-21.
6. Hashitani H, Brading AF. Electrical properties of detrusor smooth muscles fromthe pig and human urinary bladder. Br J Pharmacol.2003;140(1):146-58.
7. Sui GP, Wu C, Fry CH. The electrophysiological properties of cultured andfreshly isolated detrusor smooth muscle cells. J Urol.2001;165(2):627-32.
8. Poh YC, Corrias A, Cheng N, Buist ML. A quantitative model of human jejunalsmooth muscle cell electrophysiology. PLOS ONE.2012;7(8):e42385.
9. Blatt AH, Brammah S, Tse V, Chan L. Transurethral prostate resection in patientswith hypocontractile detrusor--what is the predictive value of ultrastructuraldetrusor changes. J Urol.2012;188(6):2294-9.
10. Neuhaus J, Wolburg H, Hermsdorf T, Stolzenburg JU, Dorschner W. Detrusorsmooth muscle cells of the guinea-pig are functionally coupled via gap junctionsin situ and in cell culture. Cell Tissue Res.2002;309(2):301-11.
11. Wang X, Caroline M, Hubert J.[Evidence of occurrence of gap junctions in stablenonobstructed human bladder]. Zhonghua Yi Xue Za Zhi.2007;87(22):1556-8.
12.杨志刚,何汇海.膀胱平滑肌不稳定研究进展.现代泌尿外科杂志.2011;01):86-87.
13. Mirone V, Imbimbo C, Longo N, Fusco F. The detrusor muscle: an innocentvictim of bladder outlet obstruction. Eur Urol.2007;51(1):57-66.
14. Andersson KE. Detrusor myocyte activity and afferent signaling. NeurourolUrodyn.2010;29(1):97-106.
15. Haefliger JA, Tissieres P, Tawadros T, et al. Connexins43and26aredifferentially increased after rat bladder outlet obstruction. Exp Cell Res.2002;274(2):216-25.
16. Wang Y, Wang K, Li H, Chen L, Xu F, Wu T. Effects of different sustainedhydrostatic pressures on connexin43in human bladder smooth muscle cells. UrolInt.2013;90(1):75-82.
17. John H, Wang X, Wehrli E, Hauri D, Maake C. Evidence of gap junctions in thestable nonobstructed human bladder. J Urol.2003;169(2):745-9.
18. Opisso E, Borau A, Rodriguez A, Hansen J, Rijkhoff NJ. Patient controlled versusautomatic stimulation of pudendal nerve afferents to treat neurogenic detrusoroveractivity. J Urol.2008;180(4):1403-8.
19. Sellers DJ, Chess-Williams R. Muscarinic agonists and antagonists: effects on theurinary bladder. Handb Exp Pharmacol.2012;208):375-400.
20. Kuhn A, Stadlmayr W, Monga A, Cameron I, Anthony F. A pilot study ofConnexin43(Cx43) in human bladder tissue in patients with idiopathic detrusoroveractivity. Eur J Obstet Gynecol Reprod Biol.2008;141(1):83-6.
21. Sangkum P, Charermsanyakorn P, Kijvikai K, Kongcharoensombat W, KochakarnW. Ultrastructural study of the detrusor in end stage renal disease. J Med AssocThai.2011;94(10):1218-23.
22. Iizuka M, Kimura K, Wang S, et al. Distinct distribution and localization ofRho-kinase in mouse epithelial, muscle and neural tissues. Cell Struct Funct.2012;37(2):155-75.
23. Hashitani H, Fukuta H, Takano H, Klemm MF, Suzuki H. Origin and propagationof spontaneous excitation in smooth muscle of the guinea-pig urinary bladder. JPhysiol.2001;530(Pt2):273-86.
24. Miyazato M, Sugaya K, Nishijima S, et al. Changes of bladder activity andconnexin43-derived gap junctions after partial bladder-outlet obstruction in rats.Int Urol Nephrol.2009;41(4):815-21.
25. Wang Y, Wang K, Li H, Chen L, Xu F, Wu T. Effects of different sustainedhydrostatic pressures on connexin43in human bladder smooth muscle cells. UrolInt.2013;90(1):75-82.
26. Li L, Jiang C, Hao P, Li W, Song C, Song B. Changes of gap junctional cell-cellcommunication in overactive detrusor in rats. Am J Physiol Cell Physiol.2007;293(5):C1627-35.
27. Thevenin AF, Kowal TJ, Fong JT, Kells RM, Fisher CG, Falk MM. Proteins andmechanisms regulating gap-junction assembly, internalization, and degradation.Physiology (Bethesda).2013;28(2):93-116.
28.陶霞,张树辉,苏定冯.细胞缝隙连接与心血管疾病.生理科学进展.2001;32(4):371-377.
29. Johnson KE, Mitra S, Katoch P, Kelsey LS, Johnson KR, Mehta PP.Phosphorylation on Ser-279and Ser-282of connexin43regulates endocytosis andgap junction assembly in pancreatic cancer cells. Mol Biol Cell.2013;24(6):715-33.
30. Lee SM, Clemens MG. Glucagon increases gap junctional intercellularcommunication via cAMP in the isolated perfused rat liver. Shock.2004;22(1):82-7.
31. Yu J, Wu J, Bagchi IC, Bagchi MK, Sidell N, Taylor RN. Disruption of gapjunctions reduces biomarkers of decidualization and angiogenesis and increasesinflammatory mediators in human endometrial stromal cell cultures. Mol CellEndocrinol.2011;344(1-2):25-34.
32. Mitic LL, Schneeberger EE, Fanning AS, Anderson JM. Connexin-occludinchimeras containing the ZO-binding domain of occludin localize at MDCK tightjunctions and NRK cell contacts. J Cell Biol.1999;146(3):683-93.
33. Karasinski J, Galas J, Semik D, Fiertak A, Bilinska B, Kilarski WM. Changes ofconnexin43expression in non-pregnant porcine myometrium correlate withprogesterone concentration during oestrous cycle. Reprod Domest Anim.2010;45(6):959-66.
34. Petrocelli T, Lye SJ. Regulation of transcripts encoding the myometrial gapjunction protein, connexin-43, by estrogen and progesterone. Endocrinology.1993;133(1):284-90.
35. Chung D, Loch CR.2,2'-Dichlorobiphenyl decreases amplitude andsynchronization of uterine contractions through MAPK1-mediatedphosphorylation of GJA1(connexin43) and inhibition of myometrial gapjunctions. Biol Reprod.2005;73(5):974-82.
36. Liang JY, Wang SM, Chung TH, Yang SH, Wu JC. Effects of18-glycyrrhetinicacid on serine368phosphorylation of connexin43in rat neonatalcardiomyocytes. Cell Biol Int.2008;32(11):1371-9.
37. Boedtkjer E, Kim S, Aalkjaer C. Endothelial alkalinisation inhibits gap junctioncommunication and endothelium-derived hyperpolarisations in mouse mesentericarteries. J Physiol.2013;591(Pt6):1447-61.
2.阚海东,黄薇,陈秉衡.中国城市大气污染和健康影响研究的回顾和展望.第四届国家环境与健康论坛论文集.2009.
3. van DA, Martin RV, Brauer M, et al. Global estimates of ambient fine particulatematter concentrations from satellite-based aerosol optical depth: development andapplication. Environ Health Perspect.2010;118(6):847-55.
4. Terzano C, Di SF, Conti V, Graziani E, Petroianni A. Air pollution ultrafineparticles: toxicity beyond the lung. Eur Rev Med Pharmacol Sci.2010;14(10):809-21.
5. Castranova V, Ma JY, Yang HM, et al. Effect of exposure to diesel exhaustparticles on the susceptibility of the lung to infection. Environ Health Perspect.2001;109Suppl4(609-12.
6. Ghio AJ, Smith CB, Madden MC. Diesel exhaust particles and airwayinflammation. Curr Opin Pulm Med.2012;18(2):144-50.
7. Lee GB, Brandt EB, Xiao C, et al. Diesel exhaust particles induce cysteineoxidation and s-glutathionylation in house dust mite induced murine asthma.PLOS ONE.2013;8(3):e60632.
8. Fortoul TI, Rodriguez-Lara V, Gonzalez-Villalva A, et al. Vanadium inhalation ina mouse model for the understanding of air-suspended particle systemicrepercussion. J Biomed Biotechnol.2011;2011(951043.
9.杨学礼,黄建凤.大气颗粒物污染对心血管系统的影响及其机制研究进展.中华预防医学杂志.2011;45(8):749-751.
10. Michael S, Montag M, Dott W. Pro-inflammatory effects and oxidative stress inlung macrophages and epithelial cells induced by ambient particulatematter.LID-S0269-7491(13)00041-9[pii]LID-10.1016/j.envpol.2013.01.026[doi]. Environ Pollut.2013;
11. Larsson N, Brown J, Stenfors N, et al. Airway inflammatory responses to dieselexhaust in allergic rhinitics. Inhal Toxicol.2013;25(3):160-7.
12. Salvi SS, Nordenhall C, Blomberg A, et al. Acute exposure to diesel exhaustincreases IL-8and GRO-alpha production in healthy human airways. Am J RespirCrit Care Med.2000;161(2Pt1):550-7.
13. Ku SK, Bae JS. Concentration dependent anti-inflammatory effects thrombin onpolyphosphate-mediated inflammatory responses in vitro and in vivo. InflammRes.2013;
14. Manna SK, Sarkar S, Barr J, et al. Single-walled carbon nanotube inducesoxidative stress and activates nuclear transcription factor-kappaB in humankeratinocytes. Nano Lett.2005;5(9):1676-84.
15.李凤菊,邵龙义,杨书申.大气颗粒物中重金属的化学特征和来源分析.中原工学院学报.2007;01):7-11.
16. Timblin C, BeruBe K, Churg A, et al. Ambient particulate matter causes activationof the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis inlung epithelial cells. Cancer Res.1998;58(20):4543-7.
17. Khatlani TS, Wislez M, Sun M, et al. c-Jun N-terminal kinase is activated innon-small-cell lung cancer and promotes neoplastic transformation in humanbronchial epithelial cells. Oncogene.2007;26(18):2658-66.
18. He X, Son SY, James K, et al. Exploring a novel ultrafine particle counter forutilization in respiratory protection studies. J Occup Environ Hyg.2013;10(4):D52-4.
19. Churg A, Gilks B, Dai J. Induction of fibrogenic mediators by fine and ultrafinetitanium dioxide in rat tracheal explants. Am J Physiol.1999;277(5Pt1):L975-82.
20.原福胜,马亚萍,赵五红,郭风华.大气颗粒物对人双核淋巴细胞微核率的影响.环境与健康杂志.2005;22(4):277-278.
21. De Flora S. Threshold mechanisms and site specificity in chromium(VI)carcinogenesis. Carcinogenesis.2000;21(4):533-41.
22. Hartwig A. Metal interaction with redox regulation: an integrating concept inmetal carcinogenesis. Free Radic Biol Med.2013;55(63-72.
23. Shields PG, Bowman ED, Harrington AM, Doan VT, Weston A. Polycyclicaromatic hydrocarbon-DNA adducts in human lung and cancer susceptibilitygenes. Cancer Res.1993;53(15):3486-92.
24. Georgiadis P, Kovacs K, Kaila S, et al. Development and validation of a directsandwich chemiluminescence immunoassay for measuring DNA adducts ofbenzo[a]pyrene and other polycyclic aromatic hydrocarbons. Mutagenesis.2012;27(5):589-97.
25.王驭良,许克新,胡浩等.北京地区成年女性膀胱过度活动症流行病学调查及对患者生活质量的影响.中华泌尿外科杂志.2010;8):550-554.
26. Palmer MH, Hardin SR, Behrend C, Collins SK, Madigan CK, Carlson JR.Urinary incontinence and overactive bladder in patients with heart failure. J Urol.2009;182(1):196-202.
27.杨为民,袁晓奕.膀胱过度活动症的诊断与治疗进展.临床泌尿外科杂志.2011;26(1):1-3.
28. Zhang ZB, Zhou DR, Song B. Gap junctional protein connexin43in rat detrusormuscle with unstable bladder. Chin Med J (Engl).2008;121(17):1698-701.
29. Onoue S, Yamamoto N, Seto Y, Yamada S. Pharmacokinetic study of nicotine andits metabolite cotinine to clarify possible association between smoking andvoiding dysfunction in rats using UPLC/ESI-MS. Drug Metab Pharmacokinet.2011;26(4):416-22.
30. Azadzoi KM, Yalla SV, Siroky MB. Oxidative stress and neurodegeneration in theischemic overactive bladder. J Urol.2007;178(2):710-5.
31. Terzano C, Di SF, Conti V, Graziani E, Petroianni A. Air pollution ultrafineparticles: toxicity beyond the lung. Eur Rev Med Pharmacol Sci.2010;14(10):809-21.
32. Sun Q, Yue P, Kirk RI, et al. Ambient air particulate matter exposure and tissuefactor expression in atherosclerosis. Inhal Toxicol.2008;20(2):127-37.
33. Brook RD, Franklin B, Cascio W, et al. Air pollution and cardiovascular disease: astatement for healthcare professionals from the Expert Panel on Population andPrevention Science of the American Heart Association. Circulation.2004;109(21):2655-71.
34. Castranova V, Ma JY, Yang HM, et al. Effect of exposure to diesel exhaustparticles on the susceptibility of the lung to infection. Environ Health Perspect.2001;109Suppl4(609-12.
35. Rao GV, Tinkle S, Weissman DN, et al. Efficacy of a technique for exposing themouse lung to particles aspirated from the pharynx. J Toxicol Environ Health A.2003;66(15):1441-52.
36. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxidedismutase. Clin Chem.1988;34(3):497-500.
37. Wendel A. Glutathione peroxidase. In: Methods Enzymol.1981, p.325-333.
38. Claiborne A. Catalase activity. In: CRC Handbook of Methods for OxygenRadical Research. Florida: Boca Raton;1985, p.283–284.
39. Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzene-induced livernecrosis. Protective role of glutathione and evidence for3,4-bromobenzeneoxide as the hepatotoxic metabolite. Pharmacology.1974;11(3):151-69.
40. Wasowicz W, Neve J, Peretz A. Optimized steps in fluorometric determination ofthiobarbituric acid-reactive substances in serum: importance of extraction pH andinfluence of sample preservation and storage. Clin Chem.1993;39(12):2522-6.
41. Lora L, Mazzon E, Martines D, et al. Hepatocyte tight-junctional permeability isincreased in rat experimental colitis. Gastroenterology.1997;113(4):1347-54.
42. Scheepe JR, de Jong BW, Wolffenbuttel KP, Arentshorst ME, Lodder P, Kok DJ.The effect of oxybutynin on structural changes of the obstructed guinea pigbladder. J Urol.2007;178(4Pt2):1807-12.
43.张文丽，崔九思，徐东群.大气中细颗粒物的污染特征及其生物效应.中国环境卫生..2003;6(1):90-102.
44.张文丽,崔九思,徐东群,戚其平.大气中细颗粒物的污染特征及其生物效应.中国环境卫生.2003;6(3):90-102.
45. Terzano C, Di SF, Conti V, Graziani E, Petroianni A. Air pollution ultrafineparticles: toxicity beyond the lung. Eur Rev Med Pharmacol Sci.2010;14(10):809-21.
46. Fortoul TI, Rodriguez-Lara V, Gonzalez-Villalva A, et al. Vanadium inhalation ina mouse model for the understanding of air-suspended particle systemicrepercussion. J Biomed Biotechnol.2011;2011(951043.
47. Parsons CL, Boychuk D, Jones S, Hurst R, Callahan H. Bladder surfaceglycosaminoglycans: an epithelial permeability barrier. J Urol.1990;143(1):139-42.
48. Cetinel S, Bl C, Ercan F, Hrda C, San T. Indomethacin-induced morphologicchanges in the rat urinary bladder epithelium. Urology.2003;61(1):236-42.
49. Cetinel S, Bl C, Ercan F, Hrda C, San T. Indomethacin-induced morphologicchanges in the rat urinary bladder epithelium. Urology.2003;61(1):236-42.
50. Soler R, Bruschini H, Freire MP, Alves MT, Srougi M, Ortiz V. Urine is necessaryto provoke bladder inflammation in protamine sulfate induced urothelial injury. JUrol.2008;180(4):1527-31.
51. Zeybek A, Saglam B, Cikler E, Cetinel S, Ercan F, Sener G. Protective effects oftaurine on protamine sulfate induced bladder damage. World J Urol.2006;24(4):438-44.
52.孟紫强,张波.二氧化硫吸入对大鼠脑组织细胞的氧化损伤作用.中国环境科学.2001;21(5):464-467.
53. Schlenker EH. An evaluation of ventilation in dystrophic Syrian hamsters. J ApplPhysiol.1984;56(4):914-21.
54. Takenaka S, Karg E, Roth C, et al. Pulmonary and systemic distribution of inhaledultrafine silver particles in rats. Environ Health Perspect.2001;109Suppl4(547-51.
55.孟紫强.二氧化硫吸入对小鼠9种脏器谷胱甘肽过氧化物酶活性的影响.环境与职业医学.2003;20(1):6-9.
56. Afaq F, Abidi P, Rahman Q. N-acetyl L-cysteine attenuates oxidant-mediatedtoxicity induced by chrysotile fibers. Toxicol Lett.2000;117(1-2):53-60.
57.杨春雪,阚海东,陈仁杰.我国大气细颗粒物水平、成分、来源及污染特征.环境与健康杂志.2011;08):735-738+753.
58. Meng Z, Zhang Q. Oxidative damage of dust storm fine particles instillation onlungs, hearts and livers of rats. Environ Toxicol Pharmacol.2006;22(3):277-82.
59. Mossman BT. Introduction to serial reviews on the role of reactive oxygen andnitrogen species (ROS/RNS) in lung injury and diseases. Free Radic Biol Med.2003;34(9):1115-6.
60. Takenaka S, Karg E, Roth C, et al. Pulmonary and systemic distribution of inhaledultrafine silver particles in rats. Environ Health Perspect.2001;109Suppl4(547-51.
61. Creutzenberg O, Bellmann B, Korolewitz R, et al. Change in agglomeration statusand toxicokinetic fate of various nanoparticles in vivo following lung exposure inrats. Inhal Toxicol.2012;24(12):821-30.
62. Dellinger B, Pryor WA, Cueto R, Squadrito GL, Hegde V, Deutsch WA. Role offree radicals in the toxicity of airborne fine particulate matter. Chem Res Toxicol.2001;14(10):1371-7.
63. Robertson S, Gray GA, Duffin R, et al. Diesel exhaust particulate inducespulmonary and systemic inflammation in rats without impairing endothelialfunction ex vivo or in vivo. Part Fibre Toxicol.2012;9(9.
64. Haefliger JA, Tissieres P, Tawadros T, et al. Connexins43and26aredifferentially increased after rat bladder outlet obstruction. Exp Cell Res.2002;274(2):216-25.
65. Fraser SE, Green CR, Bode HR, Gilula NB. Selective disruption of gap junctionalcommunication interferes with a patterning process in hydra. Science.1987;237(4810):49-55.
66. Deans MR, Volgyi B, Goodenough DA, Bloomfield SA, Paul DL. Connexin36isessential for transmission of rod-mediated visual signals in the mammalian retina.Neuron.2002;36(4):703-12.
67. Kelsell DP, Dunlop J, Stevens HP, et al. Connexin26mutations in hereditarynon-syndromic sensorineural deafness. Nature.1997;387(6628):80-3.
68. Abascal F, Zardoya R. Evolutionary analyses of gap junction protein families.Biochim Biophys Acta.2013;1828(1):4-14.
69. Nagaraja S, Kapela A, Tsoukias NM. Intercellular communication in the vascularwall: a modeling perspective. Microcirculation.2012;19(5):391-402.
70. Paul M, Wichter T, Gerss J, et al. Connexin Expression Patterns inArrhythmogenic Right Ventricular Cardiomyopathy.LID-S0002-9149(13)00395-0[pii]LID-10.1016/j.amjcard.2013.01.299[doi]. Am JCardiol.2013;
71. Lubitz SA, Ellinor PT. A common connexion between gap junctions, singlenucleotide polymorphisms, and atrial fibrillation. Can J Cardiol.2013;29(1):3-5.
72.陶霞,张树辉,苏定冯.细胞缝隙连接与心血管疾病.生理科学进展.2001;32(4):371-377.
73. Salameh A, Dhein S. Adrenergic control of cardiac gap junction function andexpression. Naunyn Schmiedebergs Arch Pharmacol.2011;383(4):331-46.
74. Yamanaka I, Kuraoka A, Inai T, Ishibashi T, Shibata Y. Differential expression ofmajor gap junction proteins, connexins26and32, in rat mammary glands duringpregnancy and lactation. Histochem Cell Biol.2001;115(4):277-84.
75. Shibata Y, Kumai M, Nishii K, Nakamura K. Diversity and molecular anatomy ofgap junctions. Med Electron Microsc.2001;34(3):153-9.
76. Kim SJ, Park EY, Hwang TK, Kim JC. Therapeutic effects of connexin inhibitorson detrusor overactivity induced by bladder outlet obstruction in rats. Urology.2011;78(2):475.e1-7.
77. Neuhaus J, Weimann A, Stolzenburg JU, Wolburg H, Horn LC, Dorschner W.Smooth muscle cells from human urinary bladder express connexin43in vivo andin vitro. World J Urol.2002;20(4):250-4.
78. Asamoto M, Takahashi S, Imaida K, Shirai T, Fukushima S. Increased gapjunctional intercellular communication capacity and connexin43and26expression in rat bladder carcinogenesis. Carcinogenesis.1994;15(10):2163-6.
79. Sakai T, Kasahara K, Tomita K, Ikegaki I, Kuriyama H.5-Hydroxytryptamine-induced bladder hyperactivity via the5-HT2A receptor inpartial bladder outlet obstruction in rats. Am J Physiol Renal Physiol.2013;304(7):F1020-7.
80. Sui GP, Coppen SR, Dupont E, et al. Impedance measurements and connexinexpression in human detrusor muscle from stable and unstable bladders. BJU Int.2003;92(3):297-305.
81. Spray DC. Gap junction proteins: where they live and how they die. Circ Res.1998;83(6):679-81.
82. Perez-Armendariz EM, Cruz-Miguel L, Coronel-Cruz C, et al. Connexin36isexpressed in beta and connexins26and32in acinar cells at the end of thesecondary transition of mouse pancreatic development and increase during fetaland perinatal life. Anat Rec (Hoboken).2012;295(6):980-90.
83. Muller-Borer BJ, Cascio WE, Esch GL, Grisham JW, Anderson PA, Malouf NN.Acquired cell-to-cell coupling and "cardiac-like" calcium oscillations in adultstem cells in a cardiomyocyte microenvironment. Conf Proc IEEE Eng Med BiolSoc.2006;1(576-9.
84.孙彧,张丽娉,陈仁华,邹云增,李毅刚.缺氧大鼠乳鼠心肌细胞中sema3a调节connexin43磷酸化水平的相关性研究.国际心血管病杂志.2011;38(5):301-304.
85. Fialova M, Dlugosova K, Okruhlicova L, Kristek F, Manoach M, Tribulova N.Adaptation of the heart to hypertension is associated with maladaptive gapjunction connexin-43remodeling. Physiol Res.2008;57(1):7-11.
86. Jongen WM, Fitzgerald DJ, Asamoto M, et al. Regulation of connexin43-mediated gap junctional intercellular communication by Ca2+in mouseepidermal cells is controlled by E-cadherin. J Cell Biol.1991;114(3):545-55.
87.张卫泽,王方正.心肌细胞缝隙连接及其与心血管疾病和心律失常的关系.中国心脏起搏与心电生理杂志.2002;16(2):146-149.
88. Miyoshi H, Boyle MB, MacKay LB, Garfield RE. Gap junction currents incultured muscle cells from human myometrium. Am J Obstet Gynecol.1998;178(3):588-93.
89. Ciray HN, Guner H, Hakansson H, Tekelioglu M, Roomans GM, Ulmsten U.Morphometric analysis of gap junctions in nonpregnant and term pregnant humanmyometrium. Acta Obstet Gynecol Scand.1995;74(7):497-504.
90. Albrecht JL, Atal NS, Tadros PN, et al. Rat uterine myometrium contains the gapjunction protein connexin45, which has a differing temporal expression patternfrom connexin43. Am J Obstet Gynecol.1996;175(4Pt1):853-8.
91. Kirchhoff S, Kim JS, Hagendorff A, et al. Abnormal cardiac conduction andmorphogenesis in connexin40and connexin43double-deficient mice. Circ Res.2000;87(5):399-405.
92. Kirchhoff S, Kim JS, Hagendorff A, et al. Abnormal cardiac conduction andmorphogenesis in connexin40and connexin43double-deficient mice. Circ Res.2000;87(5):399-405.
93.周逢海.缝隙连接介导的细胞间通讯及其与逼尿肌不稳定关系的实验研究.金锡御,主编.外科学(泌尿外).第三军医大学,2004.
94. Haefliger JA, Castillo E, Waeber G, et al. Hypertension increases connexin43in atissue-specific manner. Circulation.1997;95(4):1007-14.
95. Haefliger JA, Meda P, Formenton A, et al. Aortic connexin43is decreased duringhypertension induced by inhibition of nitric oxide synthase. Arterioscler ThrombVasc Biol.1999;19(7):1615-22.
96. Wang TL, Tseng YZ, Chang H. Regulation of connexin43gene expression bycyclical mechanical stretch in neonatal rat cardiomyocytes. Biochem Biophys ResCommun.2000;267(2):551-7.
97. Lindner P, Mattiasson A, Persson L, Uvelius B. Reversibility of detrusorhypertrophy and hyperplasia after removal of infravesical outflow obstruction inthe rat. J Urol.1988;140(3):642-6.
98. Okada S, Kojima Y, Hamamoto S, Mizuno K, Sasaki S, Kohri K. Dietary soyisoflavone replacement improves detrusor overactivity of ovariectomized ratswith altered connexin-43expression in the urinary bladder. BJU Int.2009;103(10):1429-35.
99. Imamura M, Kanematsu A, Yamamoto S, et al. Basic fibroblast growth factormodulates proliferation and collagen expression in urinary bladder smooth musclecells. Am J Physiol Renal Physiol.2007;293(4):F1007-17.
100.司徒镇强，吴军正.《细胞培养》.北京:世界图书出版公司;
101. Li L, Jiang C, Hao P, Li W, Song C, Song B. Changes of gap junctional cell-cellcommunication in overactive detrusor in rats. Am J Physiol Cell Physiol.2007;293(5):C1627-35.
102.祁琨,邓芙蓉,郭新彪.纳米二氧化钛颗粒对人肺成纤维细胞缝隙连接通讯的影响.北京大学学报（医学版）.2009;41(3):297-301.
103. Reits EA, Neefjes JJ. From fixed to FRAP: measuring protein mobility andactivity in living cells. Nat Cell Biol.2001;3(6):E145-7.
104. Campbell JH, Campbell GR. Smooth muscle phenotypic modulation--a personalexperience. Arterioscler Thromb Vasc Biol.2012;32(8):1784-9.
105. Sui GP, Wu C, Fry CH. The electrophysiological properties of cultured andfreshly isolated detrusor smooth muscle cells. J Urol.2001;165(2):627-32.
106. Harriss DR. Smooth muscle cell culture: a new approach to the study of humandetrusor physiology and pathophysiology. Br J Urol.1995;75Suppl1(18-26.
107. Baskin LS, Howard PS, Duckett JW, Snyder HM, Macarak EJ. Bladder smoothmuscle cells in culture: I. Identification and characterization. J Urol.1993;149(1):190-7.
108. Suson KD, Stec AA, Shimoda LA, Gearhart JP. Initial characterization ofexstrophy bladder smooth muscle cells in culture. J Urol.2012;188(4Suppl):1521-7.
109. Wade MH, Trosko JE, Schindler M. A fluorescence photobleaching assay of gapjunction-mediated communication between human cells. Science.1986;232(4749):525-8.
110. Nagaraja S, Kapela A, Tsoukias NM. Intercellular communication in the vascularwall: a modeling perspective. Microcirculation.2012;19(5):391-402.
111. Wu J, Taylor RN, Sidell N. Retinoic acid regulates gap junction intercellularcommunication in human endometrial stromal cells through modulation of thephosphorylation status of connexin43. J Cell Physiol.2013;228(4):903-10.
112. Hashitani H, Fukuta H, Takano H, Klemm MF, Suzuki H. Origin and propagationof spontaneous excitation in smooth muscle of the guinea-pig urinary bladder. JPhysiol.2001;530(Pt2):273-86.
113. Santicioli P, Maggi CA. Effect of18beta-glycyrrhetinic acid on electromechanicalcoupling in the guinea-pig renal pelvis and ureter. Br J Pharmacol.2000;129(1):163-9.
114. Boedtkjer E, Kim S, Aalkjaer C. Endothelial alkalinisation inhibits gap junctioncommunication and endothelium-derived hyperpolarisations in mouse mesentericarteries. J Physiol.2013;591(Pt6):1447-61.
115. Guan BC, Si JQ, Jiang ZG. Blockade of gap junction coupling by glycyrrhetinicacids in guinea pig cochlear artery: a whole-cell voltage-and current-clampstudy. Br J Pharmacol.2007;151(7):1049-60.
116. Krutovskikh VA, Piccoli C, Yamasaki H. Gap junction intercellularcommunication propagates cell death in cancerous cells. Oncogene.2002;21(13):1989-99.
1. Jiang JX, Gu S. Gap junction-and hemichannel-independent actions of connexins.Biochim Biophys Acta.2005;1711(2):208-14.
2. Nagaraja S, Kapela A, Tsoukias NM. Intercellular communication in the vascularwall: a modeling perspective. Microcirculation.2012;19(5):391-402.
3. Morris CL. Urge urinary incontinence and the brain factor.LID-10.1002/nau.22357[doi]. Neurourol Urodyn.2012;
4. Andersson KE. Detrusor myocyte activity and afferent signaling. NeurourolUrodyn.2010;29(1):97-106.
5. Miyazato M, Sugaya K, Nishijima S, et al. Changes of bladder activity andconnexin43-derived gap junctions after partial bladder-outlet obstruction in rats.Int Urol Nephrol.2009;41(4):815-21.
6. Hashitani H, Brading AF. Electrical properties of detrusor smooth muscles fromthe pig and human urinary bladder. Br J Pharmacol.2003;140(1):146-58.
7. Sui GP, Wu C, Fry CH. The electrophysiological properties of cultured andfreshly isolated detrusor smooth muscle cells. J Urol.2001;165(2):627-32.
8. Poh YC, Corrias A, Cheng N, Buist ML. A quantitative model of human jejunalsmooth muscle cell electrophysiology. PLOS ONE.2012;7(8):e42385.
9. Blatt AH, Brammah S, Tse V, Chan L. Transurethral prostate resection in patientswith hypocontractile detrusor--what is the predictive value of ultrastructuraldetrusor changes. J Urol.2012;188(6):2294-9.
10. Neuhaus J, Wolburg H, Hermsdorf T, Stolzenburg JU, Dorschner W. Detrusorsmooth muscle cells of the guinea-pig are functionally coupled via gap junctionsin situ and in cell culture. Cell Tissue Res.2002;309(2):301-11.
11. Wang X, Caroline M, Hubert J.[Evidence of occurrence of gap junctions in stablenonobstructed human bladder]. Zhonghua Yi Xue Za Zhi.2007;87(22):1556-8.
12.杨志刚,何汇海.膀胱平滑肌不稳定研究进展.现代泌尿外科杂志.2011;01):86-87.
13. Mirone V, Imbimbo C, Longo N, Fusco F. The detrusor muscle: an innocentvictim of bladder outlet obstruction. Eur Urol.2007;51(1):57-66.
14. Andersson KE. Detrusor myocyte activity and afferent signaling. NeurourolUrodyn.2010;29(1):97-106.
15. Haefliger JA, Tissieres P, Tawadros T, et al. Connexins43and26aredifferentially increased after rat bladder outlet obstruction. Exp Cell Res.2002;274(2):216-25.
16. Wang Y, Wang K, Li H, Chen L, Xu F, Wu T. Effects of different sustainedhydrostatic pressures on connexin43in human bladder smooth muscle cells. UrolInt.2013;90(1):75-82.
17. John H, Wang X, Wehrli E, Hauri D, Maake C. Evidence of gap junctions in thestable nonobstructed human bladder. J Urol.2003;169(2):745-9.
18. Opisso E, Borau A, Rodriguez A, Hansen J, Rijkhoff NJ. Patient controlled versusautomatic stimulation of pudendal nerve afferents to treat neurogenic detrusoroveractivity. J Urol.2008;180(4):1403-8.
19. Sellers DJ, Chess-Williams R. Muscarinic agonists and antagonists: effects on theurinary bladder. Handb Exp Pharmacol.2012;208):375-400.
20. Kuhn A, Stadlmayr W, Monga A, Cameron I, Anthony F. A pilot study ofConnexin43(Cx43) in human bladder tissue in patients with idiopathic detrusoroveractivity. Eur J Obstet Gynecol Reprod Biol.2008;141(1):83-6.
21. Sangkum P, Charermsanyakorn P, Kijvikai K, Kongcharoensombat W, KochakarnW. Ultrastructural study of the detrusor in end stage renal disease. J Med AssocThai.2011;94(10):1218-23.
22. Iizuka M, Kimura K, Wang S, et al. Distinct distribution and localization ofRho-kinase in mouse epithelial, muscle and neural tissues. Cell Struct Funct.2012;37(2):155-75.
23. Hashitani H, Fukuta H, Takano H, Klemm MF, Suzuki H. Origin and propagationof spontaneous excitation in smooth muscle of the guinea-pig urinary bladder. JPhysiol.2001;530(Pt2):273-86.
24. Miyazato M, Sugaya K, Nishijima S, et al. Changes of bladder activity andconnexin43-derived gap junctions after partial bladder-outlet obstruction in rats.Int Urol Nephrol.2009;41(4):815-21.
25. Wang Y, Wang K, Li H, Chen L, Xu F, Wu T. Effects of different sustainedhydrostatic pressures on connexin43in human bladder smooth muscle cells. UrolInt.2013;90(1):75-82.
26. Li L, Jiang C, Hao P, Li W, Song C, Song B. Changes of gap junctional cell-cellcommunication in overactive detrusor in rats. Am J Physiol Cell Physiol.2007;293(5):C1627-35.
27. Thevenin AF, Kowal TJ, Fong JT, Kells RM, Fisher CG, Falk MM. Proteins andmechanisms regulating gap-junction assembly, internalization, and degradation.Physiology (Bethesda).2013;28(2):93-116.
28.陶霞,张树辉,苏定冯.细胞缝隙连接与心血管疾病.生理科学进展.2001;32(4):371-377.
29. Johnson KE, Mitra S, Katoch P, Kelsey LS, Johnson KR, Mehta PP.Phosphorylation on Ser-279and Ser-282of connexin43regulates endocytosis andgap junction assembly in pancreatic cancer cells. Mol Biol Cell.2013;24(6):715-33.
30. Lee SM, Clemens MG. Glucagon increases gap junctional intercellularcommunication via cAMP in the isolated perfused rat liver. Shock.2004;22(1):82-7.
31. Yu J, Wu J, Bagchi IC, Bagchi MK, Sidell N, Taylor RN. Disruption of gapjunctions reduces biomarkers of decidualization and angiogenesis and increasesinflammatory mediators in human endometrial stromal cell cultures. Mol CellEndocrinol.2011;344(1-2):25-34.
32. Mitic LL, Schneeberger EE, Fanning AS, Anderson JM. Connexin-occludinchimeras containing the ZO-binding domain of occludin localize at MDCK tightjunctions and NRK cell contacts. J Cell Biol.1999;146(3):683-93.
33. Karasinski J, Galas J, Semik D, Fiertak A, Bilinska B, Kilarski WM. Changes ofconnexin43expression in non-pregnant porcine myometrium correlate withprogesterone concentration during oestrous cycle. Reprod Domest Anim.2010;45(6):959-66.
34. Petrocelli T, Lye SJ. Regulation of transcripts encoding the myometrial gapjunction protein, connexin-43, by estrogen and progesterone. Endocrinology.1993;133(1):284-90.
35. Chung D, Loch CR.2,2'-Dichlorobiphenyl decreases amplitude andsynchronization of uterine contractions through MAPK1-mediatedphosphorylation of GJA1(connexin43) and inhibition of myometrial gapjunctions. Biol Reprod.2005;73(5):974-82.
36. Liang JY, Wang SM, Chung TH, Yang SH, Wu JC. Effects of18-glycyrrhetinicacid on serine368phosphorylation of connexin43in rat neonatalcardiomyocytes. Cell Biol Int.2008;32(11):1371-9.
37. Boedtkjer E, Kim S, Aalkjaer C. Endothelial alkalinisation inhibits gap junctioncommunication and endothelium-derived hyperpolarisations in mouse mesentericarteries. J Physiol.2013;591(Pt6):1447-61.
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