MMI-0100对大鼠良性前列腺增生的抑制作用及其机制

Inhibitory Effect and Its Mechanism of MMI-0100 on Benign Prostatic Hyperplasia in Rats

目的探讨MMI-0100对良性前列腺增生大鼠的影响及其机制。方法雄性大鼠随机分为3组:正常对照组、模型对照组和MMI-0100组,各6只。通过手术去势和皮下注射丙酸睾酮建立良性前列腺增生模型。MMI-0100组给予40μg·kg^(-1) MMI-0100腹腔注射。测定大鼠前列腺指数。苏木精-伊红(HE)染色和马松(Masson)染色观察前列腺增生和胶原沉积。免疫组织化学、Western blotting和实时荧光定量聚合酶链反应(qPCR)检测前列腺波形蛋白和α-平滑肌肌动蛋白(α-SMA)的表达以及mRNA水平,评价前列腺上皮-间质转化(EMT)。Western blotting测定丝裂原活化蛋白激酶活化蛋白激酶2(MK2)、磷酸化MK2(p-MK2)、P38、p-P38和转化生长因子(TGF)-β_(1)的蛋白表达水平。结果模型对照组和MMI-0100组前列腺指数分别为(3.51±0.14)×10^(-2),(3.12±0.10)×10^(-2)(P<0.05)。MMI-0100组胶原沉积和EMT明显抑制,MK2的磷酸化水平下调,TGF-β_(1)的表达明显抑制。结论MMI-0100对大鼠良性前列腺增生具有抑制作用,其机制可能是抑制P38/MK2/TGF-β_(1)信号通路。

Objective To investigate the effects of MMI-0100 in benign prostatic hyperplasia(BPH)rats and its underlying mechanisms.Methods The male rats were randomly divided into 3 groups(n=6),the normal control group,the model control group and MMI-0100 group.Rat model of BPH was induced by castration and subcutaneous injection of testosterone propionate.MMI-0100 group was intraperitoneally injected with MMI-010040μg·kg^(-1).The prostate index was calculated based on the weight of body and prostate.Prostatic hyperplasia and collagen deposition were observed by HE and Masson stain.Prostatic epithelial-mesenchymal transition(EMT)was evaluated by detecting the expression and mRNA levels of vmentin andα-SMA via immunohistochemical staining,Western blotting and qPCR.Additionally,the expression of MK2,phosphorylated-MK2(p-MK2),P38,p-P38 and TGF-β_(1) were tested by Western blotting.Results Compared with the model control group(3.51±0.14)×10^(-2),MMI-0100 reduced prostate index(3.12±0.10)×10^(-2)(P<0.05),inhibited prostatic collagen deposition and EMT,as well as decreased the expression of p-MK2 and TGF-β_(1).Conclusion MMI-0100 can attenuate prostatic fibrosis via inhibiting P38/MK2/TGF-β_(1) signaling pathway.