防粘汤对宫腔粘连大鼠TGF-β1/Smad信号通路的影响

Effects of Fangzhan Decoction on TGF-β1/Smad signaling pathway in rats with intrauterine adhesions

目的:探讨防粘汤对宫腔粘连大鼠的作用及其可能机制。方法:将76只SD大鼠随机分为正常组(12只)、假手术组(12只)及造模组(52只),采用机械刮宫及感染双重损伤建立宫腔粘连大鼠模型,造模成功后,将造模组随机分为模型组、雌激素组(0.63mg·kg^(-1)·d^(-1))及防粘汤低、中、高剂量(4.14、8.28、16.56g·kg^(-1)·d^(-1))组,各10只。连续灌胃给药21d后处死大鼠,收集其双侧子宫组织,肉眼观察其大体形态学改变,HE及Masson染色检测其组织病理学变化;RT-PCR及Western Blot法检测子宫组织中TGF-β1和Smad2、Smad3、Smad7 mRNA及蛋白表达。结果:与正常组比较,模型组大鼠子宫组织肿胀,弹性差,子宫指数增高,内膜有炎症细胞浸润,重度纤维化;子宫组织中TGF-β1和Smad2、Smad3 mRNA和蛋白表达显著升高,而Smad7mRNA和蛋白表达显著降低(P<0.01)。与模型组比较,防粘汤中、高剂量组大鼠子宫形态、色泽及柔韧性明显好转,子宫指数降低,炎症及纤维化程度均下降(P<0.01);子宫组织中TGF-β1和Smad2、Smad3 mRNA和蛋白表达显著降低,Smad7 mRNA和蛋白表达显著升高(P<0.05,P<0.01)。结论:防粘汤可能通过阻断TGF-β1/Smad信号通路延缓子宫内膜纤维化进程,促进内膜修复。

Objective:To explore the treatment and pathogenesis of Fangzhan Decoction (FZD) in rats with intrauterine adhesion.Methods:Seventy-six SD rats were randomly divided into normal group (n=12),sham operation group (n=12) and model group (n=52).The rat models of intrauterine adhesions were established using mechanical injury and infection.After the establishment of the model,the modeling group were randomly divided into positive control group and FZD at a dose of4.14,8.28,16.56g·kg^(-1)·d^(-1) respectively daily for 21d.The rats were then sacrificed and uterine tissues were collected.Gross morphological changes were observed;The pathological changes and fibrosis of the uterine tissues were observed by HE staining and Masson staining;Real-time quantitative PCR and Western Blot method were used to detect the expression of key factors in TGF-β1/Smad signaling pathway in uterus tissue.Results:Compared with the control group,the uterus of the model group was swollen,distorted,with poor elasticity,the uterine/body coefficient was increased,the inflammation and fibrosis were aggravated.The levels of TGF-β1,Smad2,Smad3 mRNA and protein were significantly increased,while Smad7 was decreased markedly(P<0.01) in the model group.Compared with the model group,the uterus shape,color and flexibility of the rats in the medium and high dose groups were significantly improved,the uterine/body was decreased,the degree of inflammation and fibrosis were alleviated(P<0.01).The levels of TGF-β1,Smad2,Smad3 mRNA and protein were significantly decreased,and the levels of Smad7 mRNA and protein expression were significantly increased (P<0.05,P<0.01).Conclusion:FZD could slow down the process of uterine fibrosis,and promote the regeneration of endometrium,the mechanism may be related to block TGF-β1/Smad signaling pathway.