神经激肽B及其受体-3激活p38MAPK信号系统与子痫前期发病机制
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摘要
目的1.研究正常妊娠、子痫前期胎盘组织中神经激肽B(neurokinin B, NKB)及其受体(neurokinin B receptor, NKR)在蛋白和mRNA水平的表达,以及正常妊娠、子痫前期孕妇血浆中神经激肽B的含量,籍此探讨神经激肽B和子痫前期的关系；
2.研究活化状态的p38MAPK蛋白在正常与子痫前期胎盘中的表达,探讨NKB与p-p38MAPK表达的相关性。
方法选择正常妊娠、轻度子痫前期、重度子痫前期患者各20例,采用酶联免疫吸附法(ELISA)定量检测孕妇血浆中NKB含量；采用伊红—苏木素(HE)染色,光镜观察正常妊娠和子痫前期胎盘结构的病理学改变；用免疫组织化学检测胎盘组织中NKB/NKR、p38MAPK蛋白的定位及定量表达；用逆转录聚合酶链反应(reverse transcription polymerasechain reaction, RT-PCR)检测胎盘组织中NKB/NKR mRNA的表达。
结果1.轻度及重度子痫前期孕妇血浆中NKB水平明显高于正常孕妇；
2.正常妊娠胎盘中NKB/NKR少量分布于合体滋养细胞、毛细血管内皮细胞,主要表达于胞浆和胞膜,p-p38MAPK少量分布于滋养细胞、毛细血管内皮细胞,主要表达于胞核；正常妊娠胎盘、轻度子痫前期、重度子痫前期组NKB表达分别为：0.078±0.005、0.082±0.011、0.101±0.022,轻、重度子痫前期胎盘中NKB蛋白表达较正常妊娠显著升高(P<0.05,P<0.01)；正常妊娠胎盘、轻度子痫前期、重度子痫前期组NKR表达分别为：0.069±0.054、0.076±0.110、0.090±0.120,轻、重度子痫前期胎盘中NKR蛋白表达较正常妊娠显著升高(P<0.05,P<0.05)；正常妊娠胎盘、轻度子痫前期、重度子痫前期组p-p38MAPK蛋白分别为：0.052±0.012、0.069±0.054、0.094±0.047,轻、重度子痫前期胎盘中p-p38MAPK蛋白表达较正常妊娠显著升高(P<0.05,P<0.01),；且正常妊娠胎盘中NKB与p-p38MAPK表达呈正相关(r=0.503,p<0.05)；轻、重度子痫前期组中,NKB与p-p38MAPK水平亦呈正相关(r=0.515,p<0.05及r=0.657,p<0.01);
3.正常妊娠胎盘中NKB与NKR3 mRNA表达水平分别是：0.560±0.248、0.441±0.206,而子痫前期中NKB与NKR3表达水平均明显增加,NKB轻度子痫前期组为0.772±0.142,重度子痫前期组为0.954±0.237 NKR3轻度子痫前期组为0.578±0.253,重度子痫前期组为0.804±0.316。
结论NKB/NKR表达增高与子痫前期密切相关,p-p38MAPK与NKB/NKR的上调表达相互影响,可能是其参与子痫前期发病重要机制之一。目的1.研究缺氧对人早孕绒毛滋养细胞株(TEV-1) NKB/MKR3表达的影响；以及缺氧、P38MAPK抑制剂SB203580对P38MAPK激酶活性的影响,从细胞水平探讨NKB/MKR3、P38MAPK与子痫前期的关系；
2.研究缺氧、SB203580干预对TEV-1细胞株凋亡、增殖能力的改变,深入研究缺氧、P38MAPK对滋养细胞生物学特性的调控。
方法1.采用cocl2体外诱导TEV-1细胞化学缺氧,模拟滋养细胞体外缺氧模型,采用RT-PCR检测TEV-1中NKB/NKR3的mRNA表达；另外,分别用cocl2和SB203580干预TEV-1细胞株,研究TEV-1细胞中P38MAPK激酶活性的变化；
2.采用二氯化钴、SB203580体外干预TEV-1细胞株后,流式细胞术检测不同时间点细胞凋亡率,噻唑兰(Methl thiazolyl tetrazolium, MTT)比色法测定不同时间点滋养细胞增殖力。
结果1.随着缺氧时间的增加,滋养细胞NKB/NKR3 mRNA表达逐渐增加,至24小时达峰值,与缺氧1h、6h、12h相比显著升高,与正常培养24h相比也显著升高,其后缓慢下降；另外,cocl2处理滋养细胞20分钟后呈浓度依赖性地激活p38MAPK,而p38MAPK的选择性抑制剂SB203580呈浓度依赖性抑制p38MAPK的激酶活性；
2.随着缺氧时间的延长滋养细胞早期凋亡率逐渐增加,尤其从24h开始(24h、48h、72h)与正常培养相比,凋亡率显著升高,而p38MAPK的选择性抑制剂SB可减弱缺氧诱导的滋养细胞早期凋亡率增加；随缺氧干预时间的延长,滋养细胞的增殖能力均受不同程度抑制,培养24h抑制滋养细胞增殖最明显,而p-p38MAPK抑制剂SB可减弱CoCl2对滋养细胞的增殖抑制作用。
结论1.缺氧可诱导TVE-1细胞高表达NKB/NKR3,亦可呈浓度依赖性激活p38MAPK激酶活性；
2.随缺氧时间增加,滋养细胞凋亡率逐渐增加,增殖能力逐渐下降,而SB可减弱缺氧对滋养细胞的二者作用,说明p38MAPK通路在缺氧诱导滋养细胞凋亡率增加和增殖力下降中发挥重要作用。
目的研究NKB、SB203580对TEV-1细胞株侵袭力的影响,探求NKB、p38MAPK在子痫前期中的可能调控机制。
方法1.研究NKB及SB203580对p38MAPK激酶活性的影响；
2.研究不同浓度NKB、不同干预时间对TEV-1细胞株侵袭力的影响；
3.研究SB203580对TEV-1细胞株侵袭力的影响。
结果1.滋养细胞中NKB呈浓度依赖性激活p38MAPK,而p38MAPK的选择性抑制剂SB203580呈浓度依赖性抑制NKB对p38MAPK的激活；
2.剂量依赖性分析表明,经不同浓度NKB处理48小时,滋养细胞侵袭指数随NKB浓度的增高而降低,0.8mg/L NKB作用48h后,滋养细胞侵袭力最弱；时间依赖性分析表明,经0.8mg/L NKB分别处理12、24、48小时,滋养细胞侵袭指数随NKB干预时间的延长而降低,干预48小时,滋养细胞侵袭力最弱；
3.NKB可抑制TEV-1细胞的体外侵袭作用；单独给予SB203580能抑制滋养细胞的侵袭,SB203580亦能明显减弱NKB对滋养细胞的侵袭抑制作用。
结论滋养细胞中NKB呈浓度依赖性激活p38MAPK,呈浓度、时间依赖性的抑制TEV-1细胞的侵袭力,而p38MAPK抑制剂SB203580可减弱NKB对滋养细胞的侵袭抑制作用。说明NKB可通过p38MAPK通路调控滋养细胞的体外侵袭能力。
Objective 1. To investigate the expression of neukinin B(NKB)/neuokinin B receptor(NKR) in placentas obtained from normal pregnancy and preeclampsia, and the relationship between NKB and preeclampsia; and the plasma NKB levels from normal and preeclampsia pregnant women;
2. To investigate the the correlation of NKB and p-p38MAPK on the pathogenic mechanism of preeclampsia by detecting the expression of activating p38MAPK in placentas obtained from normal pregnancy and preeclampsia pregnant women;
Methods 1.20 nomal pregnant women,20 mild preeclampsia, and 20 severe preeclampsia women were enrolled in the study, enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of plasma NKB levels from normal and preeclampsia women;
2. HE staining observed the pathology changes in placental tissues from normal and preeclampsia women; Immuno-histochemistry observed the expression of NKB/NKR, p-p38MAPK protein in placentas, and reverse transcript polymerase chain reaction (RT-PCR) were used to detect the expression of NKB/NKR3 mRNA in placental tissues from 20 normal pregnant women and 40 preeclampsia patients.
Result 1. The plasma NKB level in the preeclampsia was significantly higher than that of normal pregnancy;
2. Under the microscopic examination, nodules of syncytiotrophoblast, fibrinoid necrosis and damage of umbilical venous endomembrane were observed by HE staining. However, these microstructural changes are rarely found in the normal placenta; The positive staining of NKB/NKR were mainly located at cell membrane, and cytoplasma of trophoblast, p-p38MAPK protein were mainly located at nuclear membrane of trophoblast. The levels of NKB/NKR expression of placenta from preeclampsia patients were significant higher than that of normal group, the levels of p-p38MAPK protein expression of placenta from preeclampsia patients were higher than that of normal group; and there was obvious positive correlation between NKB and p-p38MAPK protein from normal and preeclampsia women;
3. Contrast with normal group, the expression of NKB and NKR3 mRNA in preeclampsia group was significantly higher.
Conclusion The increase levels of NKB/NKR may play an important role in the pathogenic mechanism of preeclampsia. The activation of p38MAPK signal pathway interaction with the over expression of NKB may play an important role in the pathgenic mechanism of preeclampsia.
Objective 1. Investigating the effect of CoCl2 induced hypoxia on the expression of NKB/NKR3 of human first-trimester extravillous trophoblast cell line(TEV-1) in order to evaluate the role of NKB/NKR3 in preeclampsia. To investigate the effects of the activation of p38MAPK which was intervened by hypoxia, inhibition of p38MAPK(SB203580);
2. To investigate the effects of CoCl2 induced hypoxia, SB203580 on the apoptosis and proliferation of trophoblast in order to further study the regulation of NKB and p38MAPK on the biological characteristics of trophoblast.
Methods 1. TEV-1 was cultured respectively in normal and hypoxia circumstance which induced by CoCl2. RT-PCR was used to detect expression of NKB/NKR3 mRNA of TEV-1; the activation of p38MAPK was detected by cell ELISA after the intervention of CoCl2 and SB203580;
2. TEV-1 was cultured respectively in CoCl2 and SB203580 circumstance, flowcytomery was performed to evaluate apoptosis of TEV-1 at different time, methl thiazolyl tetrazolium(MTT) was performed to evaluate proliferation of TEV-1 at different time.
Result 1. The levels of NKB/NKR3 mRNA in TEV-1 of both groups increase gradually as the culturing time goes on, and they all go to the top at the 24-hour cultured time. Hypoxia could up-regulate the expression of NKB/NKR3. In TEV-1 cells, p38MAPK was activated by CoCl2 in a dose-dependent manner, and SB203580 could weaken the p38MAPK activation also in a dose-dependent manner;
2. Under the hypoxia condition the trophoblast apoptotic rate was increase with time goes on. They all go to the top at the 24-hour cultured time, and after that decrease very tardily, and the inhibition of p38MAPK(SB203580) could weaken this effect; Under the hypoxia condition the trophoblast proliferation was decrease with time. They all go to the lowest point at the 24-hour cultured time, and after that decrease very tardily, and the inhibition of p38MAPK(SB203580) could also weaken this effect.
Conclusion 1. CoCl2 simulated hypoxia up-regulate the expression of NKB/NKR3 and activated p38MAPK in a dose-dependent manner;
2. The trophoblast apoptotic rate was increase and the proliferation was decrease with time goes on, and SB could weaken these effects. p38MAPK signal pathway may have an important role in the hypoxia induced the increase of trophoblast apoptotic rate and the decrease of trophoblast proliferation.
Objective To investigate the effects of human recombinant NKB protein, the inhibition of p38MAPK(SB203580) on the invasiveness of TEV-1, in order to further study the regulation mechanism of NKB and p38MAPK on the biological characteristics of trophoblast.
Methods 1. Cell ELISA was used to detected the activation of p38MAPK after the intervention of CoCl2 and SB203580;
2. The TEV-1 cell's invasiveness was detected by transwell at different concentration and different time culture of NKB;
3. The effect of SB on TEV-1 cell's invasiveness was detected by transwell.
Result 1. NKB up-regulate the activation of p38MAPK in a dose-dependent manner, and SB203580 could weaken the p38MAPK activation also in a dose-dependent manner;
2. The trophoblast invasiveness was decrease with the concentration of NKB increase, and the trophoblast invasiveness was decrease with the NKB cultured time goes on;
3. NKB could inhibit the in vitro invasion of TEV-1; SB203580 solely could increase the in vitro invasion of TEV-1; but NKB and SB203580 combined will decrease the in vitro invasion of TEV-1 obviously.
Conclusion NKB up-regulate the activation of p38MAPK in a dose-dependent manner, inhibit the in vitro invasion of TEV-1 in the dose-dependent and time-dependent manner; the inhibition of p38MAPK(SB203580) could weaken the inhibition invation of TEV-1. NKB coule regulate the trophoblast invasion in vitro by p38MAPK signal pathway.
2.研究活化状态的p38MAPK蛋白在正常与子痫前期胎盘中的表达,探讨NKB与p-p38MAPK表达的相关性。
方法选择正常妊娠、轻度子痫前期、重度子痫前期患者各20例,采用酶联免疫吸附法(ELISA)定量检测孕妇血浆中NKB含量；采用伊红—苏木素(HE)染色,光镜观察正常妊娠和子痫前期胎盘结构的病理学改变；用免疫组织化学检测胎盘组织中NKB/NKR、p38MAPK蛋白的定位及定量表达；用逆转录聚合酶链反应(reverse transcription polymerasechain reaction, RT-PCR)检测胎盘组织中NKB/NKR mRNA的表达。
结果1.轻度及重度子痫前期孕妇血浆中NKB水平明显高于正常孕妇；
2.正常妊娠胎盘中NKB/NKR少量分布于合体滋养细胞、毛细血管内皮细胞,主要表达于胞浆和胞膜,p-p38MAPK少量分布于滋养细胞、毛细血管内皮细胞,主要表达于胞核；正常妊娠胎盘、轻度子痫前期、重度子痫前期组NKB表达分别为：0.078±0.005、0.082±0.011、0.101±0.022,轻、重度子痫前期胎盘中NKB蛋白表达较正常妊娠显著升高(P<0.05,P<0.01)；正常妊娠胎盘、轻度子痫前期、重度子痫前期组NKR表达分别为：0.069±0.054、0.076±0.110、0.090±0.120,轻、重度子痫前期胎盘中NKR蛋白表达较正常妊娠显著升高(P<0.05,P<0.05)；正常妊娠胎盘、轻度子痫前期、重度子痫前期组p-p38MAPK蛋白分别为：0.052±0.012、0.069±0.054、0.094±0.047,轻、重度子痫前期胎盘中p-p38MAPK蛋白表达较正常妊娠显著升高(P<0.05,P<0.01),；且正常妊娠胎盘中NKB与p-p38MAPK表达呈正相关(r=0.503,p<0.05)；轻、重度子痫前期组中,NKB与p-p38MAPK水平亦呈正相关(r=0.515,p<0.05及r=0.657,p<0.01);
3.正常妊娠胎盘中NKB与NKR3 mRNA表达水平分别是：0.560±0.248、0.441±0.206,而子痫前期中NKB与NKR3表达水平均明显增加,NKB轻度子痫前期组为0.772±0.142,重度子痫前期组为0.954±0.237 NKR3轻度子痫前期组为0.578±0.253,重度子痫前期组为0.804±0.316。
结论NKB/NKR表达增高与子痫前期密切相关,p-p38MAPK与NKB/NKR的上调表达相互影响,可能是其参与子痫前期发病重要机制之一。目的1.研究缺氧对人早孕绒毛滋养细胞株(TEV-1) NKB/MKR3表达的影响；以及缺氧、P38MAPK抑制剂SB203580对P38MAPK激酶活性的影响,从细胞水平探讨NKB/MKR3、P38MAPK与子痫前期的关系；
2.研究缺氧、SB203580干预对TEV-1细胞株凋亡、增殖能力的改变,深入研究缺氧、P38MAPK对滋养细胞生物学特性的调控。
方法1.采用cocl2体外诱导TEV-1细胞化学缺氧,模拟滋养细胞体外缺氧模型,采用RT-PCR检测TEV-1中NKB/NKR3的mRNA表达；另外,分别用cocl2和SB203580干预TEV-1细胞株,研究TEV-1细胞中P38MAPK激酶活性的变化；
2.采用二氯化钴、SB203580体外干预TEV-1细胞株后,流式细胞术检测不同时间点细胞凋亡率,噻唑兰(Methl thiazolyl tetrazolium, MTT)比色法测定不同时间点滋养细胞增殖力。
结果1.随着缺氧时间的增加,滋养细胞NKB/NKR3 mRNA表达逐渐增加,至24小时达峰值,与缺氧1h、6h、12h相比显著升高,与正常培养24h相比也显著升高,其后缓慢下降；另外,cocl2处理滋养细胞20分钟后呈浓度依赖性地激活p38MAPK,而p38MAPK的选择性抑制剂SB203580呈浓度依赖性抑制p38MAPK的激酶活性；
2.随着缺氧时间的延长滋养细胞早期凋亡率逐渐增加,尤其从24h开始(24h、48h、72h)与正常培养相比,凋亡率显著升高,而p38MAPK的选择性抑制剂SB可减弱缺氧诱导的滋养细胞早期凋亡率增加；随缺氧干预时间的延长,滋养细胞的增殖能力均受不同程度抑制,培养24h抑制滋养细胞增殖最明显,而p-p38MAPK抑制剂SB可减弱CoCl2对滋养细胞的增殖抑制作用。
结论1.缺氧可诱导TVE-1细胞高表达NKB/NKR3,亦可呈浓度依赖性激活p38MAPK激酶活性；
2.随缺氧时间增加,滋养细胞凋亡率逐渐增加,增殖能力逐渐下降,而SB可减弱缺氧对滋养细胞的二者作用,说明p38MAPK通路在缺氧诱导滋养细胞凋亡率增加和增殖力下降中发挥重要作用。
目的研究NKB、SB203580对TEV-1细胞株侵袭力的影响,探求NKB、p38MAPK在子痫前期中的可能调控机制。
方法1.研究NKB及SB203580对p38MAPK激酶活性的影响；
2.研究不同浓度NKB、不同干预时间对TEV-1细胞株侵袭力的影响；
3.研究SB203580对TEV-1细胞株侵袭力的影响。
结果1.滋养细胞中NKB呈浓度依赖性激活p38MAPK,而p38MAPK的选择性抑制剂SB203580呈浓度依赖性抑制NKB对p38MAPK的激活；
2.剂量依赖性分析表明,经不同浓度NKB处理48小时,滋养细胞侵袭指数随NKB浓度的增高而降低,0.8mg/L NKB作用48h后,滋养细胞侵袭力最弱；时间依赖性分析表明,经0.8mg/L NKB分别处理12、24、48小时,滋养细胞侵袭指数随NKB干预时间的延长而降低,干预48小时,滋养细胞侵袭力最弱；
3.NKB可抑制TEV-1细胞的体外侵袭作用；单独给予SB203580能抑制滋养细胞的侵袭,SB203580亦能明显减弱NKB对滋养细胞的侵袭抑制作用。
结论滋养细胞中NKB呈浓度依赖性激活p38MAPK,呈浓度、时间依赖性的抑制TEV-1细胞的侵袭力,而p38MAPK抑制剂SB203580可减弱NKB对滋养细胞的侵袭抑制作用。说明NKB可通过p38MAPK通路调控滋养细胞的体外侵袭能力。
Objective 1. To investigate the expression of neukinin B(NKB)/neuokinin B receptor(NKR) in placentas obtained from normal pregnancy and preeclampsia, and the relationship between NKB and preeclampsia; and the plasma NKB levels from normal and preeclampsia pregnant women;
2. To investigate the the correlation of NKB and p-p38MAPK on the pathogenic mechanism of preeclampsia by detecting the expression of activating p38MAPK in placentas obtained from normal pregnancy and preeclampsia pregnant women;
Methods 1.20 nomal pregnant women,20 mild preeclampsia, and 20 severe preeclampsia women were enrolled in the study, enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of plasma NKB levels from normal and preeclampsia women;
2. HE staining observed the pathology changes in placental tissues from normal and preeclampsia women; Immuno-histochemistry observed the expression of NKB/NKR, p-p38MAPK protein in placentas, and reverse transcript polymerase chain reaction (RT-PCR) were used to detect the expression of NKB/NKR3 mRNA in placental tissues from 20 normal pregnant women and 40 preeclampsia patients.
Result 1. The plasma NKB level in the preeclampsia was significantly higher than that of normal pregnancy;
2. Under the microscopic examination, nodules of syncytiotrophoblast, fibrinoid necrosis and damage of umbilical venous endomembrane were observed by HE staining. However, these microstructural changes are rarely found in the normal placenta; The positive staining of NKB/NKR were mainly located at cell membrane, and cytoplasma of trophoblast, p-p38MAPK protein were mainly located at nuclear membrane of trophoblast. The levels of NKB/NKR expression of placenta from preeclampsia patients were significant higher than that of normal group, the levels of p-p38MAPK protein expression of placenta from preeclampsia patients were higher than that of normal group; and there was obvious positive correlation between NKB and p-p38MAPK protein from normal and preeclampsia women;
3. Contrast with normal group, the expression of NKB and NKR3 mRNA in preeclampsia group was significantly higher.
Conclusion The increase levels of NKB/NKR may play an important role in the pathogenic mechanism of preeclampsia. The activation of p38MAPK signal pathway interaction with the over expression of NKB may play an important role in the pathgenic mechanism of preeclampsia.
Objective 1. Investigating the effect of CoCl2 induced hypoxia on the expression of NKB/NKR3 of human first-trimester extravillous trophoblast cell line(TEV-1) in order to evaluate the role of NKB/NKR3 in preeclampsia. To investigate the effects of the activation of p38MAPK which was intervened by hypoxia, inhibition of p38MAPK(SB203580);
2. To investigate the effects of CoCl2 induced hypoxia, SB203580 on the apoptosis and proliferation of trophoblast in order to further study the regulation of NKB and p38MAPK on the biological characteristics of trophoblast.
Methods 1. TEV-1 was cultured respectively in normal and hypoxia circumstance which induced by CoCl2. RT-PCR was used to detect expression of NKB/NKR3 mRNA of TEV-1; the activation of p38MAPK was detected by cell ELISA after the intervention of CoCl2 and SB203580;
2. TEV-1 was cultured respectively in CoCl2 and SB203580 circumstance, flowcytomery was performed to evaluate apoptosis of TEV-1 at different time, methl thiazolyl tetrazolium(MTT) was performed to evaluate proliferation of TEV-1 at different time.
Result 1. The levels of NKB/NKR3 mRNA in TEV-1 of both groups increase gradually as the culturing time goes on, and they all go to the top at the 24-hour cultured time. Hypoxia could up-regulate the expression of NKB/NKR3. In TEV-1 cells, p38MAPK was activated by CoCl2 in a dose-dependent manner, and SB203580 could weaken the p38MAPK activation also in a dose-dependent manner;
2. Under the hypoxia condition the trophoblast apoptotic rate was increase with time goes on. They all go to the top at the 24-hour cultured time, and after that decrease very tardily, and the inhibition of p38MAPK(SB203580) could weaken this effect; Under the hypoxia condition the trophoblast proliferation was decrease with time. They all go to the lowest point at the 24-hour cultured time, and after that decrease very tardily, and the inhibition of p38MAPK(SB203580) could also weaken this effect.
Conclusion 1. CoCl2 simulated hypoxia up-regulate the expression of NKB/NKR3 and activated p38MAPK in a dose-dependent manner;
2. The trophoblast apoptotic rate was increase and the proliferation was decrease with time goes on, and SB could weaken these effects. p38MAPK signal pathway may have an important role in the hypoxia induced the increase of trophoblast apoptotic rate and the decrease of trophoblast proliferation.
Objective To investigate the effects of human recombinant NKB protein, the inhibition of p38MAPK(SB203580) on the invasiveness of TEV-1, in order to further study the regulation mechanism of NKB and p38MAPK on the biological characteristics of trophoblast.
Methods 1. Cell ELISA was used to detected the activation of p38MAPK after the intervention of CoCl2 and SB203580;
2. The TEV-1 cell's invasiveness was detected by transwell at different concentration and different time culture of NKB;
3. The effect of SB on TEV-1 cell's invasiveness was detected by transwell.
Result 1. NKB up-regulate the activation of p38MAPK in a dose-dependent manner, and SB203580 could weaken the p38MAPK activation also in a dose-dependent manner;
2. The trophoblast invasiveness was decrease with the concentration of NKB increase, and the trophoblast invasiveness was decrease with the NKB cultured time goes on;
3. NKB could inhibit the in vitro invasion of TEV-1; SB203580 solely could increase the in vitro invasion of TEV-1; but NKB and SB203580 combined will decrease the in vitro invasion of TEV-1 obviously.
Conclusion NKB up-regulate the activation of p38MAPK in a dose-dependent manner, inhibit the in vitro invasion of TEV-1 in the dose-dependent and time-dependent manner; the inhibition of p38MAPK(SB203580) could weaken the inhibition invation of TEV-1. NKB coule regulate the trophoblast invasion in vitro by p38MAPK signal pathway.
引文
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