黄芪总皂苷对实验性脑出血大鼠脑水肿与神经功能的影响及作用机制
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摘要
目的观察黄芪总皂苷对实验性脑出血大鼠脑水肿与神经功能的影响及作用机制。方法将大鼠分为假手术组,模型组和黄芪总皂苷低、中、高剂量组,制备脑出血模型,在造模成功1 d后分别腹腔注射给予50、100、200 mg/kg的黄芪总皂苷溶液,每日1次,持续给予7 d,假手术组和模型组给予等量生理盐水。在实验结束时进行神经功能缺损评分和脑含水量测定,Western blotting法检测脑水肿周围组织中Bax、Bcl-2和Caspase-3蛋白的表达量,TUNEL法检测脑水肿周围组织中细胞凋亡情况。结果给予黄芪总皂苷干预后,与模型组比较,大鼠神经功能评分增高,脑组织含水量降低,差异有统计学意义(P <0.05)。与假手术组比较,模型组大鼠脑水肿周围组织中Bax和Caspase-3蛋白表达水平及细胞凋亡率增加,Bcl-2蛋白表达水平降低,差异有统计学意义(P <0.05);给予黄芪总皂苷干预后,与模型组比较,大鼠脑水肿周围组织中Bax和Caspase-3蛋白表达水平及细胞凋亡率降低,Bcl-2蛋白表达水平增高,且具有一定剂量依赖性,差异有统计学意义(P <0.05)。结论黄芪总皂苷能减轻实验性脑出血大鼠脑水肿和保护神经功能,这种作用可能是通过抑制脑细胞凋亡有关。
Objective: To investigate the effect and mechanism of total saponins of astragalus on brain edema and neurological function in experimental cerebral hemorrhage rats. Methods: Rats were divided into sham operation group(normal saline),the model group(normal saline) and total saponins of Astragalus low(50 mg/kg),medium(100 mg/kg) and high dose(200 mg/kg) groups. All the treatment was once a day for 7 days. The neurological defect scores and cerebral tissue moisture content were detected. Moreover,the protein expression levels of Bax,Bcl-2 and Caspase-3 in the surrounding tissues of brain edema were also detected. Thereafter,the cell apoptosis was detected by TUNEL method. Results: Compared with the sham-operated group,the expression of Bax and Caspase-3 protein and apoptotic rate increased,while the expression of Bcl-2 protein decreased in the surrounding tissues of brain edema in the model group;the difference was statistically significant(P < 0.05). After the intervention of astragaloside,compared with the model group,the neurological function score of rats increased and the water content of brain tissue decreased(P < 0.05). The expression level of Bax and Caspase-3 protein and apoptotic rate decreased,while the expression level of Bcl-2 protein increased in rats with brain edema,which was dose-dependent and the difference was statistically significant(P < 0.05). Conclusion: Total saponins of Astragalus membranaceus can alleviate brain edema and protect nerve function in experimental cerebral hemorrhage rats,which may be related to inhibition of apoptosis of brain cells.
Objective: To investigate the effect and mechanism of total saponins of astragalus on brain edema and neurological function in experimental cerebral hemorrhage rats. Methods: Rats were divided into sham operation group(normal saline),the model group(normal saline) and total saponins of Astragalus low(50 mg/kg),medium(100 mg/kg) and high dose(200 mg/kg) groups. All the treatment was once a day for 7 days. The neurological defect scores and cerebral tissue moisture content were detected. Moreover,the protein expression levels of Bax,Bcl-2 and Caspase-3 in the surrounding tissues of brain edema were also detected. Thereafter,the cell apoptosis was detected by TUNEL method. Results: Compared with the sham-operated group,the expression of Bax and Caspase-3 protein and apoptotic rate increased,while the expression of Bcl-2 protein decreased in the surrounding tissues of brain edema in the model group;the difference was statistically significant(P < 0.05). After the intervention of astragaloside,compared with the model group,the neurological function score of rats increased and the water content of brain tissue decreased(P < 0.05). The expression level of Bax and Caspase-3 protein and apoptotic rate decreased,while the expression level of Bcl-2 protein increased in rats with brain edema,which was dose-dependent and the difference was statistically significant(P < 0.05). Conclusion: Total saponins of Astragalus membranaceus can alleviate brain edema and protect nerve function in experimental cerebral hemorrhage rats,which may be related to inhibition of apoptosis of brain cells.
引文
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[2]Carlson M.Subclinical atrial fibrillation and the risk of stroke[J].New England Journal of Medicine,2016,374(10):998-1008.
[3]Hui LI,Dai X,Hou D,et al.Clinical efficacy of early microporous surgery in treatment of patients with encephaledema after small-and moderate-volume basal ganglia hemorrhage and its influence on serum inflammatory factors[J].Journal of Clinical Medicine in Practice,2017,19(4):231-244.
[4]Xie RX,Li DW,Liu XC,et al.Carnosine attenuates brain oxidative stress and apoptosis after intracerebral hemorrhage in rats[J].Neurochemical Research,2017,42(2):541-551.
[5]Li Z,He Q,Zhai X,et al.Foxo1-mediated inflam matory response after cerebral hemorrhage in rats[J].Neuroscience Letters,2016,629(17):131-136.
[6]Mavroudis CD,Karlsson M,Ko T,et al.Cerebral mitochondrial dysfunction associated with deep hypothermic circulatory arrest in neonatal swine[J].European journal of cardio-thoracic surgery:official journal of the European Association for Cardio-thoracic Surgery,2018,54(1):162-168.
[7]冯路,薛跃华,徐正保,等.抑制NF-κB对脑出血大鼠神经损伤的影响及相关机制[J].中国病理生理杂志,2017,33(12):2278-2282.
[8]裴志萍,牛文革,柴静波,等.黄芪预处理对大鼠肠系膜缺血再灌注损伤后氧化应激和炎症反应的抑制作用[J].中国中医急症,2016,25(6):967-970.
[9]Garcia JH,Wagner S,Liu KF,et al.Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats.Statistical validation[J].Stroke,1995,26(4):627-634.
[10]赵晓勇,张晓丽,江向明.Ⅳ胶原酶结合自体血构建脑出血性脑水肿大鼠实验模型[J].中华行为医学与脑科学杂志,2016,25(10):891-895.
[11]张川荛,俞志成,李树清.缺血后适应减轻树鼩缺血性脑水肿及脑梗死的机制[J].解剖学报,2017,48(2):135-141.
[12]Burda JE,Bernstein AM,Sofroniew MV.Astrocyte roles in traumatic brain injury[J].Experimental Neurology,2016,275(3):305-315.
[13]Ashkenazi A,Fairbrother WJ,Leverson JD,et al.From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors[J].Nature Reviews Drug Discovery,2017,16(4):273.
[14]Zuo D,Lin L,Liu Y,et al.Baicalin attenuates ketamine-induced neurotoxicity in the developing rats:involvement of PI3K/Akt and CREB/BDNF/Bcl-2 pathways[J].Neurotoxicity Research,2016,30(2):159-172.
[15]Dey JH,Bianchi F,Voshol J,et al.Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling,induces apoptosis,and impairs mammary tumor outgrowth and metastasis[J].Cancer Research,2016,70(10):4151-4162.
[16]Chen J,Lian X,Du J,et al.Inhibition of phosphorylated Ser473-Akt from translocating into the nucleus contributes to2-cell arrest and defective zygotic genome activation in mouse preimplantation embryogenesis[J].Development Growth&Differentiation,2016,58(3):280-292.
[17]Sun N,Wang H,Ma L,et al.Ghrelin attenuates brain injury in septic mice via PI3K/Akt signaling activation[J].Brain Research Bulletin,2016,124(15):278-285.
[18]Furelos AL,Vidal JM,Sánchez A,et al.Evidence of cellular stress and Caspase-3 resulting from a combined two-frequency signal in the cerebrum and cerebellum of sprague-dawley rats[J].Oncotarget,2016,7(40):64674-64689.
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