摘要
目的目前关于二甲双胍用于预防和治疗宫腔粘连的研究较少。文中旨在探讨二甲双胍通过调控TGF-β_(1)/Smad信号通路治疗宫腔粘连的机制研究。方法将40只大鼠分为对照组:双侧子宫未行处理,未行二甲双胍处理;建模组:刮宫联合感染法构建宫腔粘连模型,未行二甲双胍处理;二甲双胍灌胃组:刮宫联合感染法构建宫腔粘连模型,行二甲双胍灌胃[300 mg/(kg·day)],连续服用4周;二甲双胍宫腔灌注组:刮宫联合感染法构建宫腔粘连模型,行二甲双胍宫腔灌[300 mg/(kg·day)],隔日一次,连续使用4周。每组10只。荧光定量PCR及Western blot检测TGF-β_(1)/Smad信号通路中TGF-β_(1)、Smad3、MMP9、Fibronectin以及a-SMA mRNA及蛋白的表达。同时观察各组大鼠宫腔内孕囊情况。结果建模组TGF-β_(1)、Smad3、Fibronectin、a-SMA的蛋白及mRNA表达较对照组、二甲双胍灌胃组明显上调(P<0.001),MMP9蛋白及mRNA明显下降(P<0.001)。二甲双胍宫腔灌注组中TGF-β_(1)、Smad3、Fibronectin及a-SMA的mRNA表达较二甲双胍灌胃组明显下降(P<0.05),MMP9 mRNA表达明显上调(P<0.05)。同时,二甲双胍宫腔灌注组TGF-β_(1)和a-SMA的蛋白表达(0.18±0.04,0.07±0.01)较二甲双胍灌胃组(0.27±0.04,0.29±0.03)明显下调(P<0.05),MMP9蛋白明显上调(P<0.05)。对照组、建模组、二甲双胍灌胃组以及二甲双胍宫腔灌注组宫腔中孕囊数分别为(11.0±1.6)个、(3.2±0.8)个、(6.6±1.1)个以及(8.2±0.8)个,差异有统计学意义(P<0.001)。结论二甲双胍能够通过调控TGF-β_(1)/Smad信号通路逆转宫腔粘连,改善宫腔粘连大鼠生育能力,宫腔灌注效果最佳。
Objective There are few studies on the use of metformin in the prevention and treatment of intrauterine adhesion(IUA).To investigate the mechanism of the regulation of metformin to transforming growth factor-β_(1)/Smad(TGF-β_(1)/Smad)signalingpathway inIUA.Methods The IUA rat model were divided into the model group,the metformin gavage group,the metformin uterine perfusion group and the negative control group,with 10 rats in every group.Real-time polymerase chain reaction(RT-PCR)and Western Blotting were used to detect the expression levels ofTGF-β_(1)、Smad3、MMP9、Fibronectin and a-SMA among the four groups.The gestational sac of rats were observed in each group.Results Compared with control group and metformin gavagegroup,the protein and mRNA expression of TGF-β_(1),Smad3,Fibronectin,a-SMA and mRNA in model group were significantly up-regulated(P<0.001),while MMP9 protein and mRNA were significantly decreased(P<0.001).The mRNA expression of TGF-β_(1),Smad3,Fibronectin andα-SMA inthe metformin uterine perfusion group was significantly lower thanthe metformin gavage group(P<0.05),while the expression of MMP9mRNA was significantly up-regulated(P<0.05).At the same time,the protein expression of TGF-β_(1) and a-SMA in metformin intrauterine perfusion group(0.18±0.04,0.07±0.01)was significantly lower than that in metformin group(0.27±0.04,0.29±0.03)(P<0.05),while MMP9 protein was significantly up-regulated(P<0.05).The gestational sacs in the control group,the model group,the metformin gavage group and the metformin uterine perfusion group were(11.0±1.6),(3.2±0.8),(6.6±1.1)and(8.2±0.8),respectively,with statistically significant differences(P<0.001).Conclusion Metformin can reverse IUA by regulating the TGF-β_(1)/Smad signaling pathwayand improve the fertility of IUA rats.Intrauterine perfusion was more effective.
作者
丁涛
江梅
邵帅
姜经航
DING Tao;JIANG Mei;SHAO Shuai;JIANG Jing-hang(The Reproductive Medicine Center,Jingmen No.2 People's Hospital,Jingmen 448000,Hubei,China)
出处
《医学研究生学报》
CAS
北大核心
2021年第2期135-139,共5页
Journal of Medical Postgraduates
基金
湖北省自然科学基金(2018CFC859)
荆门市科学技术研究与开发计划重点项目(2019YFZD044)。
作者简介
丁涛,医学硕士;通信作者:姜经航,E-mail:yymcjjh@163.com。
