雌激素通过调节转录因子STAT-1促进大鼠前列腺组织RANTES的表达及炎症反应

摘要

AIM; To observe the activation of signal transducer and activator of transcription 1 ( STAT-1) and the expression of regulated on activation, normal T-cell expression and secreted (RANTES) in rat model of chronic nonbac-teria prostatitis induced by estrogen ( E2). METHODS: Eighty aged male rats were randomized into control group, castration group, E2 + castration group and E2 + AG490 + castration group. The pathological changes of the prostate tissues in the rats were observed under microscope with HE staining. The protein expression of STAT-1 and p-STAT-1 in rat prostate tissues was examined by Western blotting. The expression of RANTES at mRNA and protein levels was detected by RT-PCR and immunohistochemistry. The correlation between p-STAT-1 and RANTES was also analyzed. RESULTS: Obvious inflammatory reactions were found in E2 + castration group. STAT-1 protein was in activated state and the expression of RANTES at mRNA and protein levels increased in E2 + castration group as compared with control group and castration group. On the contrary, the phosphorylation of STAT-1 protein was markedly suppressed, and the mRNA and protein expression of RANTES in E2 + AG490 + castration group was notably lower than those in E2 + castration group. There was a positive correlation between the activation of STAT-1 protein and the mRNA level of RANTES (r =0.735, P <0.05) , and a positive correlation of RANTES expression between mRNA and protein levels was also observed ( r = 0. 694, P < 0. 05 ). CONCLUSION : The promotive effects of transcription factor STAT-1 on RANTES expression and inflammatory response may be involved in the molecular mechanism of estrogen-induced chronic nonbacterial prostatitis.%目的:观察雌激素(E2)诱导的大鼠慢性非细菌性前列腺炎(chronic nonbacterial prostatitis,CNP)中信号转导子及转录激活子1(signal transducer and activator of transcription l,STAT-1)的激活和调节活化正常T细胞表达及分泌因子(regulated on activation,normal T-cell expressed and secreted,RANTES)的表达,探讨雌激素诱导炎症形成的机制.方法:将80只老年雄性SD大鼠随机分为对照组、去势组、去势+E2组和去势+E2+ AG490组,每组20只.苏木素一伊红(HE)染色观察大鼠前列腺组织病理改变.Western blotting法测定STAT-1及p-STAT-1蛋白水平.RT-PCR和免疫组化SP法分别检测RANTES mRNA和蛋白表达水平,并分析p-STAT-1与RANTES表达水平的相关性.结果:去势+ E2组前列腺组织呈明显炎症表现.去势+E2组中STAT-1及p-STAT-1蛋白表达明显高于对照组及去势组(P＜0.01),RANTES mRNA和蛋白表达也显著增高(P＜0.01).去势+E2+ AG490组中STAT-1及p-STAT-1蛋白、RANTES mRNA和蛋白表达水平较去势+E2组明显降低(P＜0.01).大鼠前列腺组织中p-STAT-1表达水平与RANTES mRNA转录水平呈正相关(r=0.735,P＜0.05),RANTES表达水平与RANTESmRNA转录水平亦呈正相关(r=0.694,P＜0.05).结论:雌激素诱导CNP的形成可能与调节转录因子STAT-1、促进RANTES分子的表达及炎症反应有关.