内质网应激与PI_(3)K/Akt和ERK1/2通路在大鼠宫腔粘连治疗中的作用

Effect of Endoplasmic Reticulum Stress and PI_(3)K/Akt and ERK1/2 Pathways in the Treatment of Intrauterine Adhesion in Rats

目的探讨内质网应激与PI_(3)K/Akt和ERK1/2信号通路在宫腔粘连治疗中的作用机制。方法将18只SD雌鼠随机分为对照组(不做任何处理)、模型组(机械损伤法构建大鼠宫腔粘连模型)及治疗组(造模后当天开始皮下注射17β-雌二醇10μg,连续7天)。通过HE及Masson染色观察大鼠子宫病理形态,免疫组化法检测CD31的表达。采用Western blot法测定子宫内质网应激凋亡相关蛋白及Akt/p-Akt和ERK/p-ERK蛋白的表达。结果与对照组比较,模型组大鼠子宫内膜腺体数量减少,纤维化面积明显增加,CD31的表达明显降低(P<0.01);模型组大鼠子宫组织中GRP78和CHOP蛋白表达显著升高,而Akt、p-Akt和ERK、p-ERK蛋白表达显著降低,差异均有统计学意义(P均<0.01)。与模型组比较,治疗组大鼠子宫内膜腺体数量增加,纤维化面积降低,CD31的表达明显增加(P<0.05);治疗组大鼠子宫组织中GRP78和CHOP蛋白含量显著减少(P<0.05),Akt、p-Akt和ERK、p-ERK蛋白表达有所增加(P<0.05)。结论17β-雌二醇可改善子宫内膜的纤维化,促进子宫内膜血管增生,其作用机制可能与内质网应激及PI_(3)K/Akt和ERK1/2信号通路相关。

Objective To investigate the possible roles of endoplasmic reticulum stress,PI_(3)K/Akt and ERK1/2 signaling pathways in the treatment of uterine adhesion.Methods Eighteen SD female rats were randomly divided into control group(without any treatment),model group(intrauterine adhesion model was established by mechanical injury)and treatment group(10μg of 17β-estradiol was injected after modeling,7 days in a row).The pathological morphology of rat uterus was observed by HE and Masson staining,and the expression of CD31 was detected by immunohistochemistry.The expression of endoplasmic reticulum stress apoptosis-related protein and Akt/p-Akt and ERK/p-ERK proteins were measured by Western blot.Results Compared with the control group,the number of endometrial glands was reduced,the area of fibrosis was significantly increased,and the expression of CD31 was significantly reduced in the model group(P<0.01).The expression of GRP78 and CHOP protein in the uterine tissues of the model group was significantly increased,while the expression of Akt,p-Akt and ERK,p-ERK protein was significantly decreased(P<0.01).When compared with the model group,the number of endometrial glands increased,the area of fibrosis decreased,and the expression of CD31 increased significantly in treatment group(P<0.05),GRP78 and CHOP protein expression were reduced in the uterine tissues of treatment group(P<0.05),while the expression of Akt,p-Akt and ERK and p-ERK proteins increased(P<0.05).Conclusion 17β-estradiol improves endometrial fibrosis and promotes endometrial vascular proliferation.The mechanism of which may be related to endoplasmic reticulum stress and PI_(3)K/Akt and ERK1/2signaling pathways.