内皮素受体阻断剂 CPU0213 改善糖尿病大鼠心肌病由抑制NADPH氧化酶所介导

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (10): 1086-1090.

内皮素受体阻断剂 CPU0213 改善糖尿病大鼠心肌病由抑制NADPH氧化酶所介导

徐明, 季晖, 戴德哉, 史艳萍, 戴茵

中国药科大学药理研究室, 南京 210009, 江苏

收稿日期:2008-06-26 修回日期:2008-07-27 出版日期:2008-10-26 发布日期:2020-10-19
通讯作者: 戴德哉,男,教授,博士生导师, 研究方向:心血管药理学。Tel:025-83271270 　E-mail:dezaidai@vip.sina .com
作者简介:徐明,男,博士生,研究方向:心血管药理学。Tel:025-83271270 　E-mail:mingxu0228@yahoo.com.cn
基金资助:
国家自然科学基金面上项目(30670760)

CPU0213, an endothelin receptor antagonist, alleviates diabetic car-diomyopathy through suppressing NADPH oxidase in rats

XU Ming , JI Hui, DAI De-zai, SHI Yan-ping, DAI Yin

Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

Received:2008-06-26 Revised:2008-07-27 Online:2008-10-26 Published:2020-10-19

摘要/Abstract

摘要： 目的: 研究糖尿病大鼠心肌病中由激活的NADPH氧化酶导致的损害,可由内皮素受体拮抗剂CPU0213逆转。方法: SD大鼠一次i.p.链脲佐菌素60 mg/kg造成大鼠糖尿病模型,治疗组在后4周给予CPU0213(100 mg/kg, p.o .)和氨基胍(100 mg/kg, p.o.)治疗,连续4周。结果: CPU0213与氨基胍降低血糖效应不明显,但可改善心肌肥厚、降低心肌内皮素-1(ET-1) 和氧化应激水平。CPU0213和氨基胍明显抑制高糖温孵的心肌细胞NADPH氧化酶p22phox和p67phox亚基的mRNA和蛋白过表达。结论: 内皮素受体拮抗剂CPU0213和氨基胍改善糖尿病大鼠心肌病,由抑制心肌中NADPH氧化酶过表达所介导。

关键词: 糖尿病, 氧化应激, NADPH氧化酶, CPU0213

Abstract: AIM: To study the activation of NAD-PH oxidase in diabetic cardiomyopathy participates in myocardial injury that is likely reversed by an endothe-lin receptor antagonist CPU0213.METHODS: Male SD rats were administrated STZ (60mg^。kg^-1 ^。d^-1,i.p.) to develop diabetes mellitus for 8 weeks. CPU0213 (100 mg/kg, p.o .) and aminoguanidine (AMI, 100 mg/kg, p.o .) were applied for 4 weeks. RESULTS: CPU0213 and AMI could significantly al-leviate myocardial hypertrophy, reduce the level of ET-1 and oxidative stress except blood glucose in diabetic rats.Over-expression of mRNA and protein of p22phox and p67phox in neonatal SD rats myocytes incubated with high glucose was suppressed by both CPU0213 and AMI.CONCLUSION: Endothelin receptor antagonist CPU0213 and AMI alleviated diabetic cardiomyopathy in rats, mediated by suppressing over-expression of NADPH oxidase in the myocardium .

Key words: diabetes, oxidase stress, NADPH ox-idase, CPU0213

中图分类号:

R965.1

徐明, 季晖, 戴德哉, 史艳萍, 戴茵. 内皮素受体阻断剂 CPU0213 改善糖尿病大鼠心肌病由抑制NADPH氧化酶所介导[J]. 中国临床药理学与治疗学, 2008, 13(10): 1086-1090.

XU Ming , JI Hui, DAI De-zai, SHI Yan-ping, DAI Yin. CPU0213, an endothelin receptor antagonist, alleviates diabetic car-diomyopathy through suppressing NADPH oxidase in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(10): 1086-1090.

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