丹红注射液对单侧输尿管梗阻大鼠肾间质纤维化的影响及机制

Effect and mechanism of Danhong Zhusheye on renal interstitial fibrosis in unilateral ureteral obstruction rats

目的观察中药丹红注射液对单侧输尿管梗阻(UUO)大鼠肾小管上皮细胞转分化(EMT)和间质炎症细胞浸润的影响及机制。方法SD大鼠60只,随机分为假手术(A组)、UUO(B组)、厄贝沙坦[50mg/(kg·d),灌胃,C组]和丹红注射液治疗组[7mL/(kg·d),腹腔注射,D组]。3、7和14d留取标本。结果①B组各时间点分化抑制因子1(Id1)mRNA和蛋白、α-SMA、NFκB和Ⅰ型胶原表达增多,上皮细胞钙黏蛋白(E-cad)表达逐渐减少(均P<0.05)。D组各时间点均反相调节上述因子表达;疗效与C组相似。②B组大量CD68+细胞流入肾间质,调节正常T细胞表达和分泌因子(RANTES)mRNA和蛋白及巨噬细胞集落刺激因子(M-CSF)表达明显上调,D组下调其表达及炎症细胞浸润,作用弱于C组(均P<0.05)。结论丹红注射液可通过抑制EMT和肾间质炎症细胞浸润,减轻肾间质纤维化。

[Objective] To investigate the influence and mechanism of Danhong Zhusheye on the expression of renal tubular epithelial mesenehymal transition （EMT） and interstitial inflammatory cell infiltration in rat with unilateral ureteral obstruction （UUO）. [Methods] The mice were randomly divided into 4 groups：sham operation （A,n = 15）, UUO （B,n =15）, UUO with irbesartan treatment（C,n =15,a dose of 50 mg/kg body weight daily by garage） and UUO with Danhong Zhusheye treatment（D,n =15, daily intraperitoneal injection a dose of 7 ml/kg）.The animals were sacrificed at day 3, 7, and 14, respectively, after the surgery. [Results] The expression of the Idl at mRNA and protein levels were significantly inereased in the B group （Ⅰ d 1 mRNA,3 d）7 d,14 d after the surgery（P 〈0.05, respectively）,which was significantly decreased by treatment with DanHong Injection. The expression of α-smooth muscle aetin （α-SMA）, NFκB（nuclear factor kappa B） and collagen Ⅰ was significantly increased while E-cadherin was decreased in rats with UUO after the surgery. Treatment with Danhong Zhusheye significantly abrogated such effects （P 〈0.05）; the therapeutic effect were similar to irbesartan. Regulated upon activation normal T cell expressed and secreted factor（RANTES） at mRNA and protein levels and M-CSF were significantly increased in the B group 3 d,7 d, 14 d after the surgery,which CD68^＋ cells infiltrated renal interstitium and aggravated renal inflammation. D group attenuated those expression and inhibit inflammatory corpuscle,which were inferior to C group（P 〈0.05, respectively）. [Conclusion] Our study shows Danhong Zhusheye can attenuated renal interstitial fibrosis in UUO rats,which may be related to the inhibition of interstitial inflammation and subsequently preventing the tubular EMT.