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福辛普利和咪达普利对糖尿病大鼠心肌保护作用的比较(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第4期
页码:
480-483
栏目:
基础研究
出版日期:
2009-06-25

文章信息/Info

Title:
Comparison between fosinopril and imidapril in protection of myocardium of diabetic rats
作者:
曹建雷熊世熙宋陈芳曹新营张晗
武汉大学中南医院心血管内科,湖北 武汉 430071
Author(s):
CAO Jian-lei XIONG Shi-xi SONG Chen-fang CAO Xin-ying ZHANG Han
Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei, China
关键词:
糖尿病心肌病心肌间质重构福辛普利咪达普利AngⅡCaspase-3
Keywords:
diabetic myocardiopathy myocardial interstitial remodeling fosinopril imidapril angiotensinII caspase-3
分类号:
R972.4
DOI:
-
文献标识码:
A
摘要:
目的 通过观察血管紧张素Ⅱ(AngⅡ)和半胱天冬蛋白酶(Caspase)-3蛋白的表达率以及Ⅰ,Ⅲ型胶原的表达,探讨福辛普利与咪达普利逆转糖尿病大鼠心肌间质重构的可能作用机制。 方法 将40只健康雄性SD大鼠随机分为正常对照组(n=10)和糖尿病组(n=30)。糖尿病组通过注射链脲佐菌素(STZ)建立糖尿病模型,成功后又随机分为糖尿病未治疗组(糖尿病对照组)、福辛普利治疗组和咪达普利治疗组,每组10只。两个治疗组分别按药品说明书的推荐剂量每天以福辛普利(10 mg/kg)水溶液灌胃和咪达普利(10 mg/kg)水溶液灌胃,正常对照组和糖尿病对照组每天以同等体积的生理盐水灌胃。给药9周后,麻醉处死动物,用放射免疫法测定心肌局部AngⅡ的含量,用ABC免疫组化染色法检测Caspase-3蛋白的表达率,用SP免疫组化染色法检测心肌间质Ⅰ,Ⅲ型胶原的含量。 结果 与正常对照组相比,糖尿病对照组与两个治疗组的左心室指数均增大(P<0.05);AngⅡ的含量、Caspase-3蛋白的表达率及Ⅰ,Ⅲ型胶原的表达均明显增加(P<0.05)。用福辛普利和咪达普利治疗后,上述指标均有显著改善;但两个治疗组相比较,各个指标没有统计学差别。结论 在糖尿病大鼠心脏中存在心肌间质重构现象,福辛普利与咪达普利均可通过降低AngⅡ的含量、Caspase-3蛋白的表达率来降低Ⅰ,Ⅲ型胶原的表达,明显改善心脏的功能,但两治疗组相比没有明显的差别。
Abstract:
AIM: To explore the possible protection mechanism of fosinopril and imidapril in reversing myocardial interstitial remodeling by observing angiotensin II (AngII) and the expression rate of caspase-3 protein, type I collagen and type III collagen. METHODS: Forty male Sprague Dawley rats were randomized into two groups: 10 in normal control group and 30 in streptozotocin-induced diabetic group. Rats in the diabetic group were subdivided into diabetic control group, fosinopril-treated group and imidapril-treated group (10 rats in each group). Fosinopril was administered at a concentration of 10 mg/kg (once daily) and imidapril was administrated at a concentration of 10 mg/kg (once daily), whereas in the diabetic control group and the normal control group, the same volume of sodium chloride was administered. Nine weeks later all rats were killed by anaesthesia. Radioimmunity was used to measure the content of AngII, ABC immunohistochemical staining was used to detect the expression rate of cysteine aspartate specific proteinase (caspase)-3 protein and SP immunohistochemical staining was used to detect the level of type I and type III collagen. RESULTS: Compared with the normal controls, left ventricular index, AngII content, expression rate of caspase-3 protein and levels of type I and type III collagen all significantly increased (P<0.05). After treatment with fosinopril and imidapril, the above indexes all improved, but no significant difference was found in the treated groups. CONCLUSION: Interstitial remodeling occurs in diabetic cardiomyopathy. Without significant difference, fosinopril and imidapril improve heart function and reduce types I and III collagen expression by decreasing the content of AngII and the expression rate of caspase-3 protein.

参考文献/References

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[4] Shan YX, Yang TL, Mestril R, et al. Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy[J]. J Biol Chem, 2003, 278(46):45492-45498.

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[7] 曹萍, 刘铭球, 熊世熙,等. 福辛普利对实验性糖尿病大鼠心肌细胞外基质的影响[J]. 第四军医大学学报, 2002, 23(9):619-622.

备注/Memo

备注/Memo:
收稿日期:2008-5-15.基金项目:湖北省卫生厅重点科技项目资助(JX2A19) 通讯作者:熊世熙,主任医师,主要从事心肌保护及糖尿病心肌病方面的研究Email:xiongshixi@126.com 作者简介:曹建雷,硕士生Email:cjl198347@126.com
更新日期/Last Update: 2009-06-15