The protective effect of Daming capsule on heart function in streptozocin-induced diabetic rats with hyperlipidemia.
Impaired heart function is the main reason for increased mortality of diabetes mellitus. Development of drugs with cardioprotective effects against diabetic myocardiopathy would benefit patients with diabetes. In this study, we tested the cardioprotective effects of Daming capsule (DMC), a traditional Chinese formula, on heart function in streptozocin (STZ)-induced diabetic rats with high fat-diet (HFD). DMC 100 mg/kg/d markedly decreased fasting blood glucose (FBG) and total cholesterol (TC), but did not affect triglycerides (TG) in diabetic rats at 30 d. The decreased heart rate (HR) and prolonged QT and PR interval induced by diabetes mellitus were significantly reversed by DMC (p<0.05). The mechanism may involve that DMC attenuated L-type calcium channel alpha(1c) subunit increasing and Kv4.2 decreasing at both mRNA and protein level in diabetic rats. Additionally, DMC could obviously ameliorate the impaired heart function of diabetic rats by decreasing elevated left ventricular end-diastolic pressure (LVEDP) and increasing the attenuated maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period (+/-dp/dt(max)). Transmission electron microscopy (TEM) results showed that myocardium injury was attenuated by DMC (100 mg/kg/d) in STZ-induced diabetic rats with HFD. In conclusion, DMC could recover the prolonged QT interval and PR interval and elevated diastolic and systolic function of diabetic heart. This protective effect may partially be mediated through affecting the mRNA and protein expression of Kv4.2 and alpha(1c) as well as preventing cardiomyocyte morphological remodeling.
Ai
Jing
J
Department of Pharmacology, Harbin Medical University, Harbin Medical University, Nangang District, Harbin, China.
Yan
Xinxin
X
Zhao
Limei
L
Lu
Yuan
Y
Liang
Feng
F
Cai
Benzhi
B
Li
Guoyu
G
Lu
Yanjie
Y
Yang
Baofeng
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000096:biosynthesis; D002214:Capsules; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects; D006949:Hyperlipidemias / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051672:Shal Potassium Channels / Q000096:biosynthesis
D001786:Blood Glucose; C504728:Cacna1c protein, rat; D020746:Calcium Channels, L-Type; D002214:Capsules; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D051672:Shal Potassium Channels