宁泌泰胶囊对良性前列腺增生模型大鼠的治疗作用及机制研究

Protective effect and mechanism of Ningmitai Capsules on benign prostatic hyperplasia rat model

目的探讨宁泌泰胶囊对良性前列腺增生(benign prostatic hyperplasia,BPH)大鼠的治疗作用及作用机制。方法SD大鼠随机分为对照组、模型组及宁泌泰胶囊低、中、高剂量(0.21、0.41、0.82 g/kg)组和非那雄胺(0.45 mg/kg)组,每组8只。大鼠隔天sc 50 mg/kg丙酸睾酮复制BPH大鼠模型,连续30 d,造模同时给予相应药物。给药结束后,称定大鼠体质量和前列腺湿质量,计算前列腺指数;采用苏木素-伊红(HE)和Masson染色观察大鼠前列腺组织病理情况及纤维化程度;免疫组化法检测大鼠前列腺组织增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)表达;免疫荧光法检测大鼠前列腺组织雄激素受体(androgen receptor,AR)和表皮生长因子(epidermal growth factor,EGF)表达;ELISA检测大鼠前列腺组织白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平。结果与对照组比较,模型组大鼠前列腺指数显著升高(P<0.001);前列腺组织病理显示被膜增厚,腺体密度增加,腺上皮分泌旺盛,形成密集的皱褶或乳头状结构;Masson染色可见间质内纤维组织增生及血管增生,前列腺组织PCNA表达显著升高(P<0.001);前列腺组织AR和EGF表达显著升高(P<0.001),IL-6和TNF-α水平显著升高(P<0.05)。与模型组比较,给予药物干预后,前列腺增生程度明显减弱,间质内纤维组织及血管增生减少,前列腺组织PCNA表达显著下降(P<0.01、0.001);前列腺组织AR和EGF表达显著降低(P<0.001),IL-6和TNF-α水平显著降低(P<0.05、0.01)。结论宁泌泰胶囊可降低BPH大鼠前列腺指数,改善增生的前列腺腺体结构,减少间质纤维组织增生,抑制BPH大鼠前列腺组织PCNA增殖。其作用机制可能与抑制前列腺组织AR、EGF表达、降低前列腺组织促炎细胞因子水平有关。

Objective To explore the therapeutic effect and mechanism of Ningmitai Capsules(宁泌泰胶囊)on benign prostatic hyperplasia(BPH)rats.Methods SD rats were randomly divided into control group,model group,Ningmitai Capsules low-,medium-,high-dose(0.21,0.41,0.82 g/kg)groups and finasteride(0.45 mg/kg)groups,with eight rats in each group.The rat model of BPH was established by sc 50 mg/kg testosterone propionate at intervals of 1 d for 30 d,and the corresponding drugs were given at the same time.After drug administration,body weight and prostate wet weight of rats were weighed,and prostate index was calculated.Hematoxylin-eosin(HE)and Masson staining were used to observe the pathological situation and fibrosis degree of prostate tissue in rats.Immunohistochemical method was used to detect the expression of proliferating cell nuclear antigen(PCNA)in prostate tissue of rats.The expressions of androgen receptor(AR)and epidermal growth factor(EGF)in prostate tissue of rats were detected by immunofluorescence.The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in prostate tissue of rats were detected by ELISA.Results Compared with control group,prostate index of rats in model group was significantly increased(P<0.001),prostate histopathology showed that basement membrane was thickened,gland density was increased,and glandular epithelium was secreted vigorously,dense folds or papillary structure was formed;Masson staining showed fibrous tissue hyperplasia and vascular hyperplasia in interstitial tissue,and the expression of PCNA in prostate tissue was significantly increased(P<0.001);The expressions of AR and EGF in prostate tissue were significantly increased(P<0.001),levels of IL-6 and TNF-α were significantly increased(P<0.05).Compared with model group,after drug intervention,the degree of hyperplasia of prostate was obviously weakened,the proliferation of interstitial fiber tissue and blood vessels were decreased,and the expression of PCNA in prostate tissue was significantly decreased(P<0.01,0.001);The expressions of AR and EGF in prostate tissue were significantly decreased(P<0.001),levels of IL-6 and TNF-α were significantly decreased(P<0.05,0.01).Conclusion Ningmitai Capsules can reduce prostate index,improve the structure of hyperplastic prostate gland,reduce interstitial fibrous tissue hyperplasia and inhibit PCNA proliferation in prostate tissue of BPH rats.Its mechanism may be related to inhibiting the expressions of AR and EGF in prostate tissue and reducing the levels of proinflammatory cytokines in prostate tissue.