中药玉夏胶囊对自发性高血压大鼠肾纤维化的改善作用及TGF-β1/Smads信号通路的影响

Effect of traditional Chinese medicine Yuxia capsule on renal fibrosis in spontaneously hypertensive rats and its relationship with TGF-β_1/Smads signaling pathway

目的:观察中药玉夏胶囊对自发性高血压大鼠(SHR)肾损伤的改善作用,并探讨其可能存在的机制。方法:14周龄雄性SHR大鼠随机分为SHR模型组(0.5%羧甲基纤维素钠,CMC-Na5 m L/kg)、玉夏胶囊高、中、低(0.6、0.3、0.15 g/kg)剂量组,每组7只。另设WKY(0.5%CMC-Na5 m L/kg)正常对照组7只,每日灌胃给药一次,连续10周。于给药前及给药后每两周尾袖法测血压;末次给药后收集大鼠24 h尿液并检测尿微量白蛋白(U-m Alb)含量;腹主动脉取血测定血清β2-微球蛋白(β2-MG)、血浆及肾组织血管紧张素Ⅱ(Ang Ⅱ)含量;HE及Masson染色观察肾脏病理组织学和胶原纤维变化;Western blot法测定肾组织TGF-β_1、Smad4、Smad7蛋白含量及Smad2/3蛋白磷酸化水平表达。结果:玉夏胶囊能明显降低SHR大鼠血压(P<0.05或P<0.01),降低Um ALb、血β2-MG含量、血浆及肾组织Ang Ⅱ水平(P<0.01),明显减轻肾脏病理组织损伤和胶原纤维沉积,上调肾组织Smad7蛋白表达,下调TGF-β_1、Smad4蛋白表达及Smad2/3蛋白磷酸化水平(P<0.01)。结论:中药玉夏胶囊能有效改善SHR大鼠肾纤维化,在一定范围内呈剂量依赖性,其机制可能与降低血压,下调Ang Ⅱ水平,抑制过度激活的TGF-β_1/Smads信号通路有关。

AIM： To observe the effect of traditional Chinese medicine Yuxia capsule （YXC） on renal fibrosis in spontaneously hypertensive rats （SHR） and its relationship with TGF-β1/Smads sig- naling pathway. METHODS： Twenty-eight 14- week-old male SHR were randomized into four groups （n =7）, i.e. SHR group （0.5% CMC-Na, 5 mL/kg）, YXC high dose group （0. 6 g/kg）, middle dose group （0.3 g/kg） and low dose group （0.15 g/kg）. Another 7 wistar-kyoto（WKY） rats were selected as normal group （0.5% CMC-Na, 5 mL/kg）. Animals in each group were intragastrically administrated with YXC once a day for consecutive 10 weeks. Blood pressure was measured before administration and every two weeks during adminis- tration by tail cuff method. After the last administra- tion 24 h urine was collected and the urine micro al-bumin （U-mALb） levels were detected. Serum levels of beta 2-microsphere protein （β2-MG）, plasma and renal tissue angiotensin Ⅱ （AngII） were meas ured. Changes of renal histology and collagen fibers were observed under HE and Masson staining. Expressions of TGF-β1, Smad4, Smad7 protein and Smad2/3 protein phosphorylation were detected in renal tissues by Western blot. RESULTS：Compared with model group, YXC significantly decreased the blood pressure of SHR, levels of U-mALb, β2-MG, plasma and renal tissue AngII （P 〈 0.01 or P 〈 0.05 ）, and it significantly ameliorated the renal pathological tissue damage and the collagen fiber deposition. Expressions of TGF-β1 , Smad4 proteins and phosphorylation of Smad2/3 protein level in YXC group were lower than those in model group, while Smad7 protein expression was higher （P 〈 0.01 ）. CONCLUSION ： Traditional Chinese medicine YXC demonstrated protective effects against renal injury in a dose-dependent manner within a certain range in SHR, of which the potential mechanism may be related to decreasing the blood pressure, down-regulating AngII level and inhibiting the excessive activation of TGF-β1/Smads signaling pathway.