刺梨黄酮对诱导大鼠肾纤维化TGF-β1/Smads信号转导干预作用及机制分析

Intervention Effect on Flavonoid of Rosaroxburgii in Induced Work of TGF-β1/Smads Signal Transduction of Rats with Renal Fibrosis and Analysis of Its Mechanism

目的:探讨观察刺梨黄酮对UUO模型大鼠肾纤维化TGF-β1/Smads信号转导干预作用,并分析其机制。方法:将75只造模成功的肾纤维化大鼠随机分为5组,即假手术组、模型对照组、氯沙坦钾组、刺梨黄酮中剂量及大剂量组,每组各15只。氯沙坦钾组给予氯沙坦钾灌胃;刺梨黄酮中剂量及大剂量组分别给予刺梨黄酮灌胃。模型组和假手术组均同时给予同等容积的生理盐水。干预14 d后,观察24 h Upro、Scr、BUN,对比各组大鼠肾脏组织TGF-β1、Smad2/3、Smad7蛋白表达水平,分析刺梨黄酮对肾纤维化大鼠作用机制。结果:干预过程中,模型组和氯沙坦钾组各有1只大鼠死亡。模型组、氯沙坦钾组、刺梨黄酮中剂量和大剂量组24 h Upro、Scr和BUN水平较假手术组显著升高(P<0.01);治疗后氯沙坦钾组、刺梨黄酮中剂量和大剂量组较模型组显著降低;与氯沙坦钾组相比,刺梨黄酮中剂量组24 h Upro、Scr和BUN表达水平无明显差异(P>0.05)。免疫组化显示模型组、氯沙坦钾组和刺梨黄酮不同剂量组中,各组TGF-β1、Smad2/3表达均明显高于假手术组(P<0.01),各治疗组的表达水平明显低于模型组(P<0.05)。各组Smad7的表达均明显低于假手术组(P<0.01),各治疗组的表达水平明显高于模型组(P<0.05)。与氯沙坦钾组比较,刺梨黄酮中剂量组TGF-β1、Smad2/3、Smad7表达水平无明显差异。结论:刺梨黄酮中剂量组可显著改善肾纤维化大鼠肾功能指标,推测和抑制TGF-β1、Smad2/3蛋白表达、激活Smad7蛋白表达有关。

Objective：To investigate the flavonoids in Rosa roxburghii Tratt on UUO rats renal fibrosis TGF beta/Smads signa- ling intervention effect and analyze its mechanism. Methods ： A toal of 75 successfully modeling renal fbrosis rats were randomly divided into 5 groups, namely sham operation group, model control group, losartan treatment group and flavonoids in Rosa rox- burghii Tratt middle dose group and high dose group, with 15 rats in each. Losartan group was given losartan orally, a dose of 10mg/（ kg·d） , the concentration of 20%. Rosa roxburghii Tratt middle dose and high dose groups were given flavonoids in Rosa roxbnrghii Tratt by intragastric administration, dose of 3G/（ kg·d） and 6G/（ kg·d） , respectively. The concentration was 3% and 6%. Both model group and sham operation group were given equal volume of normal saline. After 14 days of intervention, observe 24 hU, SCR, BUN, conpare and analyze each group＇s rats＇ kidney tissue TGF beta 1, Smad2/3 and Smad7 protein expression levels of flavonoids from Rosa roxburghii Tratt on action mechanism of renal fibrosis in rats. Results ： During the intervention, one rat died in model group and losartan potassium. Compared with sham group, model group, losartan potassium group, flavonoids dose and high dose groups＇ 24 hUPRO, Scr and BUN levels were significantly increased （P 〈 0. 01 ）. After treatment, compared with model group,losartan potassium group, flavonoids dose and high dose groups＇were significantly reduced. Compared with losartan potassium group, no significant difference in 24 hUPRO, Scr and BUN levels of expression. Immunohistochemistry showed that model group,losartan group and flavonoids different dose groups＇ TGF -β1 and Smad2/3 expressions were significantly higher than those of the sham group （ P 〈 0. 01 ）. The expression level of each treatment group significantly was lower than that of the model group （P 〈 0. 05 ）. Smad7 expressions in each group were significantly lower than that of the sham group （P 〈 0. 01 ）. The expression level of each treatment group was significantly higher than that of the model group （P 〈 O. 05 ）. Compared with losartan potassium group, middle dose group＇s flavonoids TGF- β1, Smad2/3 and Smad7 expression levels had no significant difference. Conclusion：By the result of flavonoid from Rosa roxburghii Tratt middle dose group, tlavonoid Rosa roxburghii Tratt can remark- ably improve functional index of renal fibrosis rats. We can infer that this is sbuject to the inhibition of TGF -β, Smad2/3 protein expression and activation of Smad7 protein expression.