临产前后子宫肌收缩相关蛋白在人子宫肌中的表达及相关信号转导途径的研究

Regional expression of contraction- associated proteins and related signal pathway in the human myometrium during pregnancy and labour

目的研究分析临产前后人子宫平滑肌细胞中子宫肌收缩相关蛋白的表达情况,并初步探讨分娩启动中信号转导的可能途径。方法收集足月妊娠人子宫平滑肌组织,根据是否临产分为足月动产组和足月未动产组。应用蛋白免疫印记法(Western-blot法)检测子宫平滑肌组织中的子宫收缩相关蛋白(CAPs):缝隙连接蛋白-43(CX43)、催产素受体(OTR)、环加氧酶2(COX2)的表达以及NF-κB p65、MAPK家族成员Erk1/2和它们的磷酸化水平。结果动产组中子宫平滑肌组织中收缩相关蛋白CX43、OTR、COX2的表达量明显高于未动产组(P<0.05),p-p65、p-Erk1/2蛋白表达高于未动产组(P<0.05),p65、Erk1/2蛋白表达无统计学意义(P>0.05);2、线性相关分析显示,CX43、COX2与p-p65的表达之间呈正相关(P<0.01),OTR与p-p65的表达之间呈正相关(P<0.05);COX2与p-Erk1/2的表达之间有相关性(P<0.05),CX43、OTR与p-Erk1/2的表达无显著相关(P>0.05);p-p65与p-Erk1/2无显著相关(P>0.05)。结论足月临产子宫相关收缩蛋白表达水平明显上升,提示了在分娩启动中子宫收缩相关蛋白发挥重要作用,其有助于促进子宫收缩,产程进展、使得胎儿顺利娩出。足月临产子宫平滑肌组织中磷酸化的NF-κB p65以及Erk1/2的表达水平有显著性差异,提示NF-κB介导的炎症反应通路及MAPK通路可能在子宫收缩过程中发挥作用。相关性分析提示子宫收缩相关蛋白与NF-κB介导的炎症反应通路可能共同或协同参与分娩的发生。

Objective To investigate the expression of contraction- associated proteins in human myometrium,and to explore the significance of NF- κB inflammatory process and mitogen- activated protein kinase（ MAPK） pathway in the pathogenesis of the onset of labor. Methods 12 parturients without complications at term were selected as the study group of normal labor（ NL）,and 12 health pregnant women at the same period were chosen as control（ TNL）. The levels of CX43,OTR,COX,p65,Erk1 /2 and phosphorylation of p65 and ERK1 /2 in myometrium of study and control group were determined by western blotting. Results The level of contraction- associated proteins（ CX43、OTR、COX2） in myometrium in NL group were significantly higher than those in TNL group（ P〈0. 05）,and the level of p- p65 and p- Erk had the same forms of expression（ P〈0. 05）,however,p65 and ERK protein expressions had no statistical significance（ P〈0. 05）; There were obvious positive correlations between the expressions of contraction- associated proteins（ CX43、OTR、COX2） and p- p65 in uterine smooth muscle（ P〈0. 05）,and was weak positive correlation between the expression of COX2 and p- ERK1 /2（ P〈0. 05）. The CX43 and OTR protein quantum had no correlation to the level of p- ERK（ P〉0. 05）. There was no significant correlation between p- p65 and p- Erk1 /2. Conclusion The expressions of contraction- associated proteins and p- p65 in myometrium of on- set labor women were much higher than those of non- labor＇s,and they are closely correlated. So the NF- κB inflammatory signal pathway and the increased expression of contraction- associated proteins in myometrium may be involved in the pathogenesis of the onset of labor.