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中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (6): 632-639.doi: 10.12092/j.issn.1009-2501.2018.06.006

• 基础研究 • 上一篇    下一篇

中药玉夏胶囊对自发性高血压大鼠肾纤维化的作用研究

程小龙,胡坤媚,胡浩然,徐杭杭,杨解人,韩 军   

  1. 皖南医学院药学院药理学教研室,药物研发中心,安徽省多糖药物工程技术研究中心,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:2017-12-27 修回日期:2018-05-22 出版日期:2018-06-26 发布日期:2018-06-19
  • 通讯作者: 韩军,男,教授,硕士生导师,研究方向:临床药理学。 Tel: 0553-3932517 E-mail: aku110@163.com
  • 作者简介:程小龙,男,硕士在读,研究方向:临床药理学。 Tel:05533932517 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)

Effects of Chinese medicine Yuxia capsule on renal fibrosis in spontaneously hypertensive rats

CHENG Xiaolong, HU Kunmei, HU Haoran,XU Hanghang, YANG Jieren, HAN Jun   

  1. College of Pharmacy, Third-Grade Pharmacology Laboratory of State, Administration of Traditional Chinese Medicine, Drug Research and Development Center, Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Wannan Medical College, Wuhu 241002, Anhui, China
  • Received:2017-12-27 Revised:2018-05-22 Online:2018-06-26 Published:2018-06-19

摘要:

目的:探讨中药玉夏胶囊改善自发性高血压大鼠(spontaneously hypertensive rat, SHR)肾纤维化的作用及其相关机制。方法:以WKY大鼠(WistarKyoto rat)为正常对照组(0.5%羧甲基纤维素钠,5 mL/kg);SHR大鼠随机分为SHR模型组(0.5% 羧甲基纤维素钠,5 mL/kg)、玉夏胶囊高剂量组(0.6 g/kg)、中剂量组(0.3 g/kg)及低剂量组(0.15 g/kg),每组7只。连续10周,每日灌胃给药一次。测量大鼠给药前与给药后第2、4、6、8、10周舒张压(DBP);测量给药前与给药后第3、5、8周大鼠尿量;检测血清肌酐(Scr)、尿素氮(BUN)含量;免疫组化法检测肾组织TGFβ1阳性细胞表达水平;RT-qPCR检测肾组织TGFβ1 mRNA表达水平;Western blot法检测肾组织ERK1/2、pERK1/2、P38、p-P38、MMP-9、TIMP-1蛋白表达水平。结果:玉夏胶囊能剂量依赖性地降低SHR大鼠DBP,增加尿量,降低血清中Scr和BUN含量以及肾组织中P38、ERK1/2、TGFβ1、MMP9、TIMP1蛋白表达(P<0.05, P<0.01)。结论:玉夏胶囊具有减轻SHR大鼠肾纤维化的作用且在一定范围内呈剂量依赖性,其机制可能与其利尿、降压,抑制P38/MAPK、ERK/MAPK相关通路,降低TGFβ1、MMP9、TIMP1表达水平,恢复MMP9/TIMP1比值平衡有关。

关键词: 玉夏胶囊, 自发性高血压大鼠, 肾纤维化, TGFβ1, P38/MAPK, ERK/MAPK, MMP9/TIMP1

Abstract:

AIM: To investigate the improvement of Chinese medicine Yuxia capsule on renal fibrosis in spontaneously hypertensive rats (SHR) and its possible mechanism. METHODS: WKYs(Wistar-Kyoto rats)were set as normal control group (0.5% CMC-Na, 5 mL/kg). SHRs were randomly divided into SHR model group (0.5% CMC-Na, 5 mL/kg), Yuxia capsule high dose group (0.6 g/kg), middle dose group (0.3 g/kg) and low dose group (0.15 g/kg). Seven rats in each group. According to the above dose, each group of rats were gavaged once daily for 10 weeks. Diastolic blood pressure (DBP) was measured before administration and 2, 4, 6, 8, 10 weeks during the drug administration by non-invasive tail arterial pressure system. Urine was collected before and 3, 5, 8 week after administration and the urine volume was measured. Automatic biochemical analyzer was utilized to measure the contents of serum creatinine (Scr) and blood urea nitrogen (BUN). Immunohistochemistry was used to detect the levels of TGF-β1 positive cells in kidney. Quantitative reverse transcription PCR (RTqPCR) was applied to detect the expression levels of TGFβ1 mRNA. Western blot was adopted to measure the expressions of ERK1/2,p-ERK1/2,P38,p-P38,MMP-9,TIMP-1 proteins in kidney. RESULTS: Yuxia capsule could dose-dependently reduce DBP and the contents of Scr and BUN, increase urine volume. Expressions of TGF-β1,MMP-9,TIMP-1 and phosphorylation of P38 and ERK1/2 protein level in Yuxia capsule group were lower than those in model group(P<0.05, P<0.01). CONCLUSION: Traditional Chinese medicine Yuxia capsule demonstrats protective effects against renal fibrosis in a dosedependent manner within a certain range in SHR, of which the mechanism may be associated with reducing diastolic blood pressure, promoting urination, inhibiting P38/MAPK, ERK/MAPK signal pathway and the expressions of TGF-β1,MMP-9 and TIMP-1, recovering the ratio of MMP-9/TIMP-1.

Key words: Yuxia capsule, spontaneous hypertensive rats, renal fibrosis, TGF-β1, P38/MAPK, ERK/MAPK, MMP-9/TIMP-1

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