盐酸小檗碱对丙酸睾酮诱导的前列腺增生小鼠的作用及其机制研究

目的研究盐酸小檗碱对丙酸睾酮诱导的前列腺增生小鼠的作用及其机制。方法使用丙酸睾酮诱导建立前列腺增生小鼠模型,造模成功后,选择雄性昆明小鼠40只,随机分为4组,分别为模型组(生理盐水组)、盐酸小檗碱低剂量(10 mg/ml)组、盐酸小檗碱中剂量(20 mg/ml)组、盐酸小檗碱高剂量(40 mg/ml)组,每组10只,连续给药10 d后,记录各组小鼠每日尿量及10 d累计尿量,计算给药前后各组小鼠体重减轻值,检测各组小鼠血浆中TNF-α、IL-6、IL-10及IL-1β水平,取小鼠前列腺组织并计算脏器指数,苏木精-伊红染色法观察各组小鼠前列腺组织病理切片,Western blot法检测各组小鼠前列腺组织中VEGF、AKT、caspase-12蛋白表达情况。结果与模型组相比,盐酸小檗碱各剂量组小鼠累计尿量呈剂量依赖性显著增加(P<0.05),且随着给药时间的延长,盐酸小檗碱各剂量组小鼠每日尿量逐渐增加;与模型组相比,连续给药10 d后,盐酸小檗碱各剂量组小鼠的体重减轻值呈剂量依赖性显著增加(P<0.05),盐酸小檗碱各剂量组小鼠体内TNF-α、IL-6、IL-10及IL-1β等炎症因子水平、前列腺脏器指数均呈剂量依赖性显著降低(P<0.05)。病理组织学检查结果显示,与模型组相比,盐酸小檗碱各剂量组细胞形态明显改善,细胞排列整齐,腺体乳头向腔内扩张明显缩小,盐酸小檗碱中、高剂量组前列腺组织细胞形态圆润,结节样增生少见,盐酸小檗碱高剂量组小鼠的前列腺组织腺体乳头无异常突出;Western blot结果表明,与模型组相比,盐酸小檗碱各剂量组小鼠前列腺组织中VEGF及AKT表达量均呈剂量依赖性显著降低(P<0.05),caspase-12表达量呈剂量依赖性显著增加(P<0.05)。结论盐酸小檗碱能够抑制丙酸睾酮诱导的前列腺增生小鼠前列腺组织的增生,其作用机制可能与调节前列腺组织VEGF、AKT及caspase-12等蛋白的表达有关。

Effect of berberine hydrochloride on testosterone propionate-induced prostatic hy-perplasia in mice and its mechanism

Objective To study the effect of berberine hydrochloride on testosterone propionate-induced be-nign prostatic hyperplasia in mice and its mechanism.Methods The mouse model of benign prostatic hyperplasia was induced by testosterone propionate.After successful establishment of the model,40 male Kunming mice were randomly divided into 4 groups:model group(physiological saline group),low-dose berberine hydrochloride(10 mg/ml)group,middle-dose berberine hydrochloride(20 mg/ml)group and high-dose berberine hydrochloride(40 mg/ml)group,10 rats in each group.After continuous administration for 10 days,the daily urine volume and cumulative urine volume of 10 days in each group were recorded,the weight loss of mice in each group was calculated before and after administration,the levels of TNF-α,IL-6,IL-10 and IL-1βin plasma were measured,and the prostate tissue was taken and the organ index was calculated.The pathological sections of prostate tissue of mice in each group were detected by hematoxylin-eosin staining;the expression of VEGF,AKT and caspase-12 protein in prostate tissue of mice in each group was detected by Western blot method.Results Compared with model group,the cumulative urine volume of berberine hydrochloride groups increased significantly in a dose-dependent manner(P<0.05),and the daily urine vol-ume of berberine hydrochloride groups increased gradually with the prolongation of administration time.Compared with model group,after 10 days of continuous administration,the weight loss of berberine hydrochloride groups increased significantly in a dose-dependent manner(P<0.05).The levels of inflammatory factors such as TNF-α,IL-6,IL-10 and IL-1βand prostate organ index decreased significantly in a dose-dependent manner in berberine hydrochloride groups(P<0.05).The results of histopathological examination showed that compared with model group,the cell mor-phology of berberine hydrochloride groups was significantly improved,the cells were arranged neatly,and the expansion of gland nipple into the lumen was significantly reduced,the morphology of prostate tissue cells was round,and nodular hyperplasia was rare in the middle-and high-dose groups of berberine hydrochloride;there was no abnormal protruding gland nipple in the high-dose group of berberine hydrochloride.Western blot results showed that compared with model group,the expression of VEGF and AKT in prostate tissue of berberine hydrochloride groups decreased significantly in a dose-dependent manner(P<0.05),while the expression of caspase-12 increased significantly in a dose-dependent manner(P<0.05).Conclusion Berberine hydrochloride can inhibit the hyperplasia of prostate tissue induced by tes-tosterone propionate in mice with benign prostatic hyperplasia,and its mechanism may be related to the regulation of the expression of VEGF,AKT and caspase-12 in prostate tissue.