克癃胶囊对前列腺增生大鼠模型及Nrf2/ARE信号通路的影响

目的:探讨克癃胶囊对丙酸睾酮诱导的大鼠前列腺增生模型的影响及抗氧化作用机制。方法:将40只雄性SD大鼠随机分为正常组,模型组,克癃胶囊低、高剂量组(3.6,7.2 g·kg-1),核因子E2相关因子2(Nrf2)干预剂组,每组8只。除正常组外,其余各组均皮下注射丙酸睾酮建立前列腺增生的大鼠模型,同时给予药物灌服,连续4周。观察不同药物对前列腺湿重、前列腺指数的影响,苏木素-伊红(HE)观察病理组织形态变化,酶联免疫吸附测定法(ELISA)检测血清样品中丙二醛(MDA)和谷胱甘肽(GSH)的含量,实时荧光定量聚合酶链式反应(Real-time PCR)检测前列腺组织中Nrf2/ARE信号通路抗氧化因子Nrf2,血细素单加氧酶-1(HO-1),醌氧化还原酶1(NQO1)mRNA的表达水平。结果:与正常组比较,模型组大鼠的前列腺湿重及前列腺指数升高,前列腺上皮皱褶增生,大鼠血清GSH含量明显降低,Nrf2,HO-1和NQO1 mRNA表达明显降低(P0.05,P0.01)。与模型组比较,克癃胶囊明显降低前列腺指数,改善前列腺上皮组织的增生,促进大鼠血清GSH的含量增加(P0.01);克癃胶囊能上调Nrf2,HO-1和NQO1的mRNA表达水平(P0.05,P0.01)。结论:克癃胶囊能明显抑制大鼠的前列腺增生,低剂量的克癃胶囊可激活Nrf2/ARE信号通路,提高机体抗氧化能力。

Effects of Kelong Capsule on Benign Prostatic Hyperplasia Rat Model and Nrf2/ARE Signaling Pathway

Objective: To investigate the effect of Kelong capsule on testosterone-induced benign prostatic hyperplasia (BPH) and its antioxidant mechanism in rats. Method: Forty male SD rats were randomly divided into normal group, model group, low-dose Kelong capsule group (3.6 g·kg^-1), high-dose Kelong capsule group (7.2 g·kg^-1) and nuclear factor E₂-related factor 2(Nrf2) intervention group, n=8 in each group. Except the rats in normal group, all the other rats received subcutaneous injections of testosterone propionate (TP) to establish BPH models. Drugs were concomitantly administered by oral gavage for 4 weeks. Then the effects of different drugs on wet weight of the prostate and prostate index (PI) were observed, and haematoxylin-eosin (HE) staining was used to observe the morphological changes. The malondialdehyde (MDA) and glutathione (GSH) contents in serum were detected by enzyme-linked immunosorbent assay(ELISA) kit. The mRNA levels of Nrf2, oxygenase-1 (HO-1) and quinone oxidoreductase (NQO1) were determined with real time fluorescent quantitative polymerase chain reaction (Real-time PCR). Result: As compared with the normal group, the wet weight of prostate and PI were increased and the prostatic epithelial was proliferated in the model group; GSH content in serum was significantly reduced; and mRNA expression levels of Nrf2, HO-1 and NQO1 were also significantly reduced (P<0.05, P<0.01). As compared with the model group, Kelong capsule significantly decreased prostate index, ameliorated the histological changes, increased the content of GSH in serum(P<0.01), and significantly up-regulated Nrf2, HO-1 and NQO1 mRNA levels (P<0.05,P<0.01). Conclusion: Kelong capsule could effectively inhibit the development of BPH, and low dose Kelong capsule could activate Nrf2/ARE signal pathway to increase the antioxidant capacity of the body.