环巴胺对良性前列腺增生大鼠Hedgehog通路相关因子的影响

Effect of cyclopamine on Hedgehog pathway related factors in rats with benign prostatic hyperplasia

目的观察环巴胺对良性前列腺增生(BPH)大鼠Hedgehog通路相关因子的影响。方法先利用丙酸睾酮诱导去势大鼠建立BPH模型,再将30只造模成功的BPH大鼠随机分为模型组(BPH组)和环巴胺组,未造模的15只大鼠为正常对照组(Normal组)。环巴胺组大鼠腹腔注射环巴胺,Normal组和BPH组腹腔注射等剂量生理盐水,1次/天,连续7 d。给药结束后处死大鼠,获得各组大鼠的前列腺组织,并对其进行各项指标的测定。结果与Normal组比较,BPH组和环巴胺组Ki-67蛋白表达水平明显升高(P<0.05);G_(0)/G_(1)期细胞比例明显减少,S期细胞比例明显增多,细胞凋亡率明显下降(P<0.05),Shh、Ptc1、Gli1、TGF-β、b-FGF、Bcl-2 mRNA及蛋白表达水平明显升高,Bax mRNA及蛋白表达水平明显下降(均P<0.05)。与BPH组比较,环巴胺组Ki-67蛋白表达水平明显下降(P<0.05);G_(0)/G_(1)期细胞比例明显增多,S期细胞比例明显减少,细胞凋亡率明显升高(P<0.05),Shh、Ptc1、Gli1、TGF-β、b-FGF、Bcl-2 mRNA及蛋白表达水平明显下降,Bax mRNA及蛋白表达水平明显升高(均P<0.05)。结论环巴胺通过阻断Hedgehog通路,减少前列腺细胞增殖并促进前列腺细胞凋亡,从而有效抑制BPH的进展。

Objective To observe the effect of cyclopamine on Hedgehog signaling pathway related factors in rats with benign prostatic hyperplasia.Methods Firstly,castrated rats were induced by testosterone propionate to establish BPH model,and then 30 successful BPH rats were randomly divided into the model group(the BPH group)and the cyclopamine group(the cyclopamine group),and 15 rats without modeling were served as normal control group(the normal group).Rats in the cyclopamine group were intraperitoneally injected with cyclopamine,and rats in the normal group and the BPH group were intraperitoneally injected with the same dose of normal saline,once a day,for seven consecutive days.After the end of administration,the rats were killed to obtain the prostate tissue of each group,and the indexes were determined.Results Compared with the normal group,the expression level of Ki-67 protein in the BPH group and the cyclopamine group increased significantly(P<0.05),the proportion of cells in G_(0)/G_(1) phase decreased significantly,the proportion of cells in S phase increased significantly,and the apoptosis rate decreased significantly(P<0.05);the expression levels of mRNA and protein of Hedgehog signaling pathway factors such as Shh,Ptc1,Gli1,TGF-β,b-FGF,Bcl-2 mRNA were significantly increased,while the expression levels of mRNA and protein of Bax were significantly decreased(all P<0.05).Compared with the BPH group,the expression level of Ki-67 protein in the cyclopamine group decreased significantly(P<0.05);the proportion of cells in G_(0)/G_(1) phase was significantly increased,the proportion of cells in S phase was significantly decreased,and the apoptosis rate was significantly increased(P<0.05).The expression levels of mRNA and protein such as Shh,Ptc1,Gli1,TGF-β,b-FGF,Bcl-2 were significantly decreased,while the expression levels of mRNA and protein of Bax were significantly increased(all P<0.05).Conclusion Cyclopamine can effectively inhibit the progression of BPH by blocking Hedgehog signaling pathway,reducing the proliferation of prostatic cells,and promoting the apoptosis of prostatic cells.