丹参酮ⅡA对大鼠肾间质纤维化的抑制作用

Inhibitive Effect 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机制。方法:30只雄性SD大鼠随机分为假手术组、模型组和丹参酮ⅡA组。结扎大鼠单侧输尿管建立肾间质纤维化动物模型。丹参酮ⅡA经腹腔注射,剂量为1.5mg/(kg·d)。术后第10天取梗阻侧肾组织作HE、Masson染色,观察肾间质病理改变。免疫组化法检测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。逆转录-聚合酶链反应(RT-PCR)检测三者的mRNA水平。结果:模型组术后第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表达显著增加(P<0.01)。丹参酮ⅡA组肾间质纤维化程度减轻,肾组织TGF-β1、α-SMA及Ⅰ型胶原表达下调(P<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。

Objective：To investigate the effect of tanshinone Ⅱ A on renal interstitial fibrosis in rats and its mechanism. Methods： Thirty male sprague-dawley rats were randomly divided into sham-operated group, model group and tanshinone Ⅱ A treated group. Animal models of renal interstitial fibrosis were established with unilateral ureteral ligation in rats. Tanshinone Ⅱ A was injected intraperitoneally with dose of 1.5mg/kg daily in tanshinone Ⅱ A-treated group. After 10 days of unilateral ureteral obstruction, all rats were killed and the obstructed kidney were collected for HE and Masson staining to check the histological changes of renal interstitial tissues. The protein expression and localization of transforming growth factor β1 （TGF-β1）, α-smooth muscle actin（α-SMA） and type Ⅰ collagen in renal tissues were detected with immunohistochemical staining. The mRNA levels of TGF-β1,α-SMA and type Ⅰ collagen were analyzed with reverse transcription-polymerase chain reaction. Results： Compared with sham-operated group,model group exhibited severe renal interstitial fibrosis and expressions of TGF-β1, α-SMA and type Ⅰ collagen were markedly higher in the obstructed kidney（P〈0. 01 ）. Treated with tanshinone Ⅱ A, renal interstitial fibrosis was less marked and levels of TGF-β1, α-SMA and type Ⅰ collagen down-regulated significantly in renal tissues（P〈0. 05）. Conclusion： Tanshinone Ⅱ A can inhibit renal interstitial fibrosis by down-regulating TGF-β1 expression, inhibiting fibroblasts proliferation and phenotypic transitions and reducing collagen sediment.