雄激素通过HMGB-1介导细胞自噬促大鼠前列腺增生

Androgen Promotes Benign Prostatic Hyperplasia in Rats by HMGB-1-mediated Autophagy

目的探讨外源性雄激素促大鼠前列腺增生的可能机制。方法72只成年雄性SD大鼠随机分为6组,每组12只,分别为对照组(Control组)、丙酸睾丸素(TP)组、高迁移率族蛋白B-1(HMGB-1)组、丙酸睾丸素+HMGB-1(TP+HMGB-1)组、TP+氯喹(CQ,自噬抑制剂)组、TP+甘草甜素(Gly,HMGB-1抑制剂)组。处理21 d后,分别测量各组大鼠体质量、前列腺体积、湿重并计算前列腺指数;HE染色法观察前列腺组织病理学变化;Western blot法检测前列腺组织LC-3bⅡ/Ⅰ、P62、Beclin-1、HMGB-1的蛋白表达水平;透射电镜法观察前列腺上皮细胞内自噬小体形成情况。结果与Control组比较,TP组大鼠前列腺体积、湿重和指数均增加(P均<0.05),上皮和间质细胞增生,LC-3bⅡ/Ⅰ、HMGB-1、Beclin-1表达上调,P62表达下调(P均<0.05),自噬小体数目增多;单独给予HMGB-1同样可以引起前列腺组织增生、自噬水平上调(P<0.05);而联合给予TP+HMGB-1将引起前列腺增生程度和细胞自噬水平进一步增加(P<0.05)。与TP组比较,联合给予TP+CQ或TP+Gly均可引起前列腺增生和自噬水平降低(P均<0.05),各指标与其他两组比较差异均无统计学意义(P均>0.05)。结论雄激素可能通过上调HMGB-1介导细胞自噬致大鼠前列腺组织增生的发生。

Objective To explore the possible mechanism of exogenous androgen in promoting benign prostatic hyperplasia(BPH)in rats.Methods A total of 72 adult male SD rats were randomly divided into 6 groups:Control group(n=12),testosterone propionate(TP)group(n=12),high mobility group box-1(HMGB-1)group,testosterone propionate and HMGB-1(TP+HMGB-1)group,TP+chloroquine(CQ,autophagy inhibitor)group and TP+glycyrrhizin(Gly,HMGB-1 inhibitor)group.After 21 days of treatment,the body weight,prostate volume,wet weight and prostate index were measured,and the histopathological changes of prostate were observed by HE staining.The protein expression levels of LC-3bⅡ/Ⅰ,P62,Beclin-1 and HMGB-1 in prostate tissue were detected by Western blot,and the formation of autophagy bodies in prostatic epithelial cells was observed by transmission electron microscope.Results Compared with Control group,the volume,wet weight and index of prostate in TP group were increased,epithelial and interstitial cell hyperplasia,the expression of LC-3bⅡ/Ⅰ,HMGB-1 and Beclin-1 were up-regulated.The expression of P62 was down-regulated,and the number of autophagy was increased.HMGB-1 alone could also induce prostate hyperplasia and autophagy.However,the degree of benign prostatic hyperplasia and the level of autophagy were further increased by combined administration of TP+HMGB-1(P all<0.05).Compared with TP group,combined administration of TP+CQ or TP+Gly could reduce the levels of benign prostatic hyperplasia and autophagy,and there was no significant difference between the two groups(P all>0.05).Conclusion Androgen may mediate the occurrence of prostate hyperplasia induced by autophagy in rats through up-regulating HMGB-1.