丹参酮ⅡA对大鼠肾间质纤维化的抑制作用(英文)

Inhibitive Effects of TanshinoneⅡA on Renal Interstitial Fibrosis in Rats

目的探讨丹参酮ⅡA对大鼠肾间质纤维化的作用及可能机制。方法雄性SD大鼠30只随机分为假手术组、模型组和丹参酮ⅡA组。假手术组仅找到输尿管,不行结扎术。模型组结扎大鼠左侧输尿管建立肾间质纤维化动物模型。丹参酮ⅡA组术前24h经腹腔注射丹参酮ⅡA,剂量为1.5mg/(kg.d),手术操作同模型组。术后第10天取梗阻侧肾组织行HE、Masson染色,观察其肾间质病理改变。免疫组织化学法检测其肾组织转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)及Ⅰ型胶原的蛋白表达与定位。反转录-聚合酶链反应(RT-PCR)检测3者mRNA水平。结果输尿管结扎术后第10天梗阻侧出现明显的肾间质纤维化,肾组织TGF-β1、α-SMA和Ⅰ型胶原的蛋白及mRNA表达均显著增加(Pa<0.01)。经丹参酮ⅡA治疗后,肾间质纤维化程度减轻,肾组织TGF-β1、α-SMA及Ⅰ型胶原表达均下调(Pa<0.05)。结论丹参酮ⅡA对大鼠肾间质纤维化有明显的抑制作用,其机制可能与下调TGF-β1表达,抑制成纤维细胞增殖和表型转化,减少胶原沉积有关。

ObjectiveTo investigate the effects of TanshinoneⅡA on renal interstitial fibrosis in rats and its mechanism.MethodsThirty male Sprague-Dawley rats were randomly divided into sham-operated group,model group and TanshinoneⅡA treated group.Rats in sham operated group did not have their left ureteral obstructed.Animal models of renal interstitial fibrosis were established with unilateral ureteral obstruction（UUO） in rats.TanshinoneⅡA was intraperitoneally injected every day with dose of 1.5 mg/kg on 24 hours before operation in TanshinoneⅡA treated group.The operation procedure in TanshinoneⅡA treated group was the same as that in the model group.After 10 days of UUO,all rats were killed and the obstructed kidney were collected for Hematoxylin-Eosin（HE） and Masson staining to check the pathological changes of renal interstitial tissues.The protein expression and localization of transforming growth factor-β,（TGF-β1）,α-smooth muscle actin（α-SMA） and typeⅠcollagen in renal tissues were detected with immunohistochemical staining.The mRNA levels of TGF-β1,α-SMA and typeⅠcollagen were analyzed with reverse transcription-polymerase chain reaction（RT-PCR）.ResultsCompared with sham-operated group,model group exhibited severe renal interstitial fibrosis and the expressions of TGF-β1,α-SMA and typeⅠcollagen were markedly higher in obstructed kidney（Pa〈0.01）.Treated with TanshinoneⅡA,renal interstitial fibrosis was ameliorated and the expression levels of TGF-β1,α-SMA and typeⅠcollagen were down-regulated significantly in renal tissues（Pa〈0.05）.ConclusionTanshinoneⅡA can inhibit renal interstitial fibrosis by down-regulating TGF-β1 expression,inhibiting fibroblasts proliferation and phenotypic transitions and reducing collagen sediment.