• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文OA文献 >Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats
【2h】

Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats

机译：N-乙酰基-丝氨酰-天冬氨酰-赖氨酰脯氨酸预防糖尿病大鼠心肌纤维化

页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a physiological tetrapeptide hydrolysed by ACE (angiotensin-converting enzyme). In experimental models of hypertension, Ac-SDKP has antifibrotic effects in the heart; however, the role of Ac-SDKP in diabetic cardiomyopathy is currently unknown. The aim of the present study was to evaluate the effect of Ac-SDKP on cardiac systolic and diastolic function, and interstitial and perivascular fibrosis in the heart of diabetic rats. Diabetes was induced in 55 Sprague-Dawley rats by streptozotocin injection. Control rats (n = 18) underwent only buffer injection. Out of the 55 diabetic rats, 19 were chronically treated with insulin and 13 with the ACEI (ACE inhibitor) ramipril (3 mg . kg(-1) of body weight . day(-1)). At 2 months after the onset of diabetes, Ac-SDKP (1 mg . kg(-1) of body weight . day(-1)) was administered by osmotic minipumps for 8 weeks to eight control rats, 13 diabetic rats, seven diabetic rats treated with ramipril and nine insulin-treated diabetic rats. Diabetic rats had a significant increase in blood glucose levels. Left ventricular interstitial and perivascular fibrosis, and TGF-beta 1 (transforming growth factor-beta 1) protein levels were increased in diabetic rats, but not in insulin-treated diabetic rats and ramipril-treated diabetic rats, compared with control rats. Ac-SDKP administration significantly reduced left ventricular interstitial and perivascular fibrosis in diabetic rats and in diabetic rats treated with ramipril. This was accompanied by a significant reduction in active TGF-beta 1 and phospho-Smad2/3 protein levels in myocardial tissue of diabetic rats. Echocardiography showed that diabetes was associated with increased end-systolic diameters, and depressed global systolic function and diastolic dysfunction, as assessed by transmitral Doppler velocity profile. These changes were completely reversed by insulin or ramipril treatment. Ac-SDKP treatment partially restored diastolic function in diabetic rats. In conclusion, Ac-SDKP administration in diabetic rats reduces left ventricular interstitial and perivascular fibrosis, active TGF-beta 1 and phospho-Smad2/3 levels, and improves diastolic function. Taken together, these findings suggest that, by inhibiting the TGF-beta/Smad pathway, Ac-SDKP protects against the development of diabetic cardiomyopathy.
机译：Ac-SDKP（N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸）是被ACE（血管紧张素转换酶）水解的生理四肽。在高血压的实验模型中，Ac-SDKP在心脏中具有抗纤维化作用。然而，目前尚不清楚Ac-SDKP在糖尿病性心肌病中的作用。本研究的目的是评估Ac-SDKP对糖尿病大鼠心脏的心脏收缩和舒张功能以及间质和血管周纤维化的影响。通过链脲佐菌素注射在55只Sprague-Dawley大鼠中诱发糖尿病。对照大鼠（n = 18）仅接受缓冲液注射。在55只糖尿病大鼠中，有19只接受了胰岛素的长期治疗，有13只接受了ACEI（ACE抑制剂）雷米普利（3 mg。kg（-1）体重。day（-1））。在糖尿病发作后2个月，通过渗透性微型泵向8只对照组大鼠，13只糖尿病大鼠，7只糖尿病大鼠施用Ac-SDKP（1 mg。kg（-1）体重。day（-1）），持续8周。雷米普利治疗的大鼠和9只胰岛素治疗的糖尿病大鼠。糖尿病大鼠的血糖水平明显升高。与对照组相比，糖尿病大鼠左心室间质和血管周纤维化以及TGF-β1（转化生长因子-β1）蛋白水平升高，但胰岛素治疗的糖尿病大鼠和雷米普利治疗的糖尿病大鼠却没有升高。在糖尿病大鼠和接受雷米普利治疗的糖尿病大鼠中，Ac-SDKP给药显着降低了左心室间质和血管周纤维化。这伴随着糖尿病大鼠心肌组织中活性TGF-β1和磷酸Smad2 / 3蛋白水平的显着降低。超声心动图显示，糖尿病与收缩末期直径增加，整体收缩功能下降和舒张功能障碍有关，如通过经颅多普勒速度分布图所评估。胰岛素或雷米普利治疗可完全逆转这些变化。 Ac-SDKP治疗可部分恢复糖尿病大鼠的舒张功能。总之，在糖尿病大鼠中使用Ac-SDKP可减少左心室间质和血管周纤维化，活跃的TGF-beta 1和磷酸Smad2 / 3的水平，并改善舒张功能。综上所述，这些发现表明，Ac-SDKP通过抑制TGF-β/ Smad途径，可预防糖尿病性心肌病的发展。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号