丝裂霉素C抑制PI3K/AKT信号通路抗宫腔黏连SD大鼠子宫内膜纤维化的机制研究

Mechanism of inhibition of PI3K/AKT signaling pathway on endometrial fibrosis in SD rats with intrauterine adhesion based on mitomycin C

目的探讨丝裂霉素C通过抑制PI3K/AKT信号通路对宫腔黏连SD大鼠内膜纤维化的作用及机制。方法将40只SD雌性大鼠按随机数字表法分为对照组、模型组、实验组1、实验组2,每组10只,建立宫腔黏连模型并进行丝裂霉素C治疗。观察各组大鼠子宫内膜组织形态变化,并行Western blot检测p-AKT、p-PI3K、Bcl-2、Bax蛋白含量。结果与对照组比较,模型组大鼠HE染色可见细胞结构紊乱,大量单层柱状上皮细胞被上皮细胞覆盖,黏膜下层腺体数量减少,细胞成纤维化增生增加;模型组大鼠子宫组织中p-AKT、p-PI3K、Bcl-2蛋白均显著升高,Bax蛋白表达显著降低,差异具有统计学意义(P<0.01)。与模型组比较,各实验组大鼠细胞胞浆及细胞核染色程度较浅,细胞成纤维化增生数量明显减少,其中以实验组2大鼠最为显著;各实验组大鼠p-AKT、p-PI3K、Bcl-2蛋白均显著降低,Bax蛋白表达显著升高(P<0.05);且实验组2大鼠p-AKT、p-PI3K、Bcl-2蛋白含量明显低于实验组1,Bax蛋白含量明显高于实验组1(P<0.05)。结论丝裂霉素C可抑制宫腔黏连大鼠成纤维细胞活力,诱导细胞凋亡,其作用机制与抑制PI3K/AKT信号通路相关蛋白有关。

Objective To investigate the effect and mechanism of mitomycin C on endometrial fibrosis in SD rats with intrauterine adhesion by inhibiting PI3K/AKT signaling pathway.Methods Forty female SD rats were randomly divided into control group,model group,experimental group 1 and experimental group 2,10 rats in each group.The model of intrauterine adhesion was established and treated with mitomycin C.The histological changes of endometrium in each group were observed,and the protein content of p-AKT,p-PI3K,Bcl-2 and Bax protein was detected by Western blot.Results Compared with control group,the HE staining of model group showed that the cell structure was disordered,a large number of monolayer columnar epithelial cells were covered by epithelial cells,the number of submucosal glands was decreased,and the proliferation of fibroblast was increased.The expression of p-AKT,PI3K and Bcl-2 protein in the uterus of model group was significantly increased,and the expression of Bax protein was significantly decreased(P<0.01).Compared with model group,the cytoplasmic and nuclear staining degree of each experimental group was lighter,and the number of fibroblast proliferation was significantly decreased,especially in the rats of experimental group 2.Compared with model group,the expression of Bax protein was significantly increased and the expression of p-AKT,p-PI3K and Bcl-2 protein was significantly decreased in each experimental group(P<0.05).Moreover,the protein contents of p-AKT,p-PI3K and Bcl-2 protein in experimental group 2 were significantly lower than those in experimental group 1(P<0.05),while the protein content of Bax was significantly higher than that in experimental group 1(P<0.05).Conclusion Mitomycin C can inhibit the cell viability and induce apoptosis in rats with intrauterine adhesions,and its mechanism is related to the inhibition of PI3K/AKT signaling pathway-related proteins.