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中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (11): 1247-1252.

• 基础研究 • 上一篇    下一篇

内皮素受体拮抗剂CPU0213 拮抗的对NADPH 氧化酶和PKCe介导的应激性肾损害

徐瑾, 戴德哉, 彭洪军, 戴茵   

  1. 中国药科大学药理研究室, 南京 210009, 江苏
  • 收稿日期:2009-06-15 修回日期:2009-09-27 发布日期:2020-10-26

Stress induced early renal injury by upregulating NADPH oxidase, hyperphosphorylation of PKCε is mitigated by endothelin receptor antagonist CPU0213

XU Jin, DAI De-zai, PENG Hong-jun, DAI Yin   

  1. Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China
  • Received:2009-06-15 Revised:2009-09-27 Published:2020-10-26
  • About author:XU Jin, female, master postgraduate, research division of pharmacology.E-mail:xujin1225@sina.com
  • Supported by:
    This work was supported by the National Natural Science Foundation(30670760) and Major State Basic Research Development Program of the People's Republic of China(2006CB503807).

摘要: 目的:应激所致的早期肾功能不全, 可能与内皮素-1(ET-1) -蛋白激酶C (PKCε) 通路的异常有关。探讨内皮素受体拮抗剂CPU0213 抑制ET系统和PKCε, 从而改善应激所致的肾功能损伤。方法:SD 大鼠, (240 ±20) g, 随机分成3 组:正常对照组、异丙肾上腺素(ISO 1 mg/kg, s.c., ×10 d) 组、ISO +CPU0213(20 mg/kg, s.c., d 6 -10)治疗。检测血清肌酐、24 h 尿白蛋白、肾皮质GSH-Px 、SOD 和MDA, 及ETA R、PKCε、NAPDH 氧化酶-p67phox 的mRNA 和蛋白表达。结果:与正常组相比, 血清肌酐和24 h 尿白蛋白浓度明显增高(P <0.01), 肾皮质GSH-Px 、SOD 活力降低, MDA增加, ETAR 、PKCε、NAPDH 氧化酶-phox67 的mRNA和蛋白表达均上调(P <0.05) 。经CPU0213干预后, 上述指标均趋于正常。结论:应激所致早期肾脏损伤中, NADPH 氧化酶表达增加和PKCε过磷酸化, 由ETAR 所介导。内皮素受体拮抗剂CPU0213 抑制氧化应激, 改善应激所致的早期肾损伤。

关键词: 内皮素受体拮抗剂剂, PKCε, NAPDH 氧化酶-p67phox, 应激, 肾损害

Abstract: AIM: Stress likely contributes to oxidative stress initiating early renal insufficiency, that may relate to abnormal endothelin-1 (ET-1) -PKC(protein kinase C) εpathway.It is aimed to test if the endothelin receptor antagonist CPU0213 could reverse stress induced renal early lesion by suppressing abnormal ET and pPKCε. METHODS: Sprague-Dawley rats were subdivided into 3 groups:(1) normal, (2) isoproterenol (ISO) 1 mg/kg, s.c.for 10 days and (3) the ISO injected rats were intervened with CPU0213 20mg/kg, s.c., at day 6 -10.Biochemical measurements and expressions of ETAR (endothelin receptor A), NADPH oxidase p67phox and PKCεwere conducted. RESULTS: Serum creatinine and 24 h urinary albumin were increased significantly (P < 0.01), compared with normal.The activities of GSHPx and SOD were decreased and the content of MDA was increased in the renal cortex associating with upregulated mRNA and protein of ETAR, PKC (, and NADPH oxidase p67phox in ISO treated rats.CPU0213 was effective to reverse the renal function by suppressing the abnormalities. CONCLUSION: Activated ETAR, NADPH oxidase and pPKCεare assocaited with renal dysfunction in response to ISO.Endothelin receptor antagonist of CPU0213 is effective in reversing these changes.

Key words: endothelin receptor antagonist, NADPH oxidase-p67phox, pPKCε, stress, renal injury

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