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

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (4): 387-393.

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

胡坤媚，胡浩然，沈媛媛，卢毅宁，杨解人，韩军

皖南医学院药理学教研室，国家中医药管理局中药药理三级实验室，芜湖 241002，安徽

收稿日期:2016-11-08 修回日期:2017-03-01 出版日期:2017-04-26 发布日期:2017-04-26
通讯作者: 韩军，男，副教授，硕士生导师，研究方向：临床药理学。 Tel:0553-3932607 E-mail:aku110@163.com
作者简介:胡坤媚，女，硕士在读，研究方向：临床药理学。 Tel:18255386304 E-mail:1220209594@qq.com
基金资助:
安徽省教育厅自然科学基金重点项目(KJ2015A157)

Effect of traditional Chinese medicine Yuxia capsule on renal fibrosis in spontaneously hypertensive rats and its relationship with TGF-β1/Smads signaling pathway

HU Kunmei, HU Haoran, SHEN Yuanyuan, LU Yining, YANG Jieren, HAN Jun

Department of Pharmacology, Third-Grade Pharmacology Laboratory of State, Administration of Traditional Chinese Medicine, Wannan Medical College, Wuhu 241002, Anhui, China

Received:2016-11-08 Revised:2017-03-01 Online:2017-04-26 Published:2017-04-26

摘要/Abstract

摘要：

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-Na 5 mL/ 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-Na 5 mL/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-mAlb）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(AngII)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-β1、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U-mALb、血β2-MG含量、血浆及肾组织AngII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-β1、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AngII水平，抑制过度激活的TGF-β1/Smads 信号通路有关。

关键词: 玉夏胶囊, 自发性高血压大鼠, 肾纤维化, 血管紧张素II, TGF-β1/Smads信号通路

Abstract:

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 signaling 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 administration by tail cuff method. After the last administration 24 h urine was collected and the urine micro albumin (U-mALb) levels were detected. Serum levels of beta 2-microsphere protein (β2-MG)， plasma and renal tissue angiotensin II (AngII) were measured. 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.

Key words: Yuxia capsule, spontaneously hypertensive rats, renal fibrosis, AngII, TGF-β1/Smads signaling pathway

中图分类号:

R965.2

胡坤媚，胡浩然，沈媛媛，卢毅宁，杨解人，韩军. 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[J]. 中国临床药理学与治疗学, 2017, 22(4): 387-393.

HU Kunmei, HU Haoran, SHEN Yuanyuan, LU Yining, YANG Jieren, HAN Jun. Effect of traditional Chinese medicine Yuxia capsule on renal fibrosis in spontaneously hypertensive rats and its relationship with TGF-β1/Smads signaling pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(4): 387-393.

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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-β1/Smads signaling pathway

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