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Protective Effect and Mechanism of Total Glucosides, Isolated from Corni Fructus on Diabetic Cardiomyopathy Rats

Author: YuSuQing
Tutor: SongBiWei；QiMinYou
School: Zhejiang University of Technology
Course: Pharmacology
Keywords: diabetic cardiomyopathy Fructus Corni pathological changes extracellular matrix oxidative stress
CLC: R285.5
Type: Master's thesis
Year: 2011
Downloads: 55
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Abstract


Diabetic cardiomyopathy (DCM) is one of the most serious and outstanding chronic complications of diabetes mellitus, which often lead to later-period heart failure and death. Fructus corni (Cornus officinalis Sieb.et Zucc.), a tradional Chinese medicine, is usually used for "Xiaoke", which means diabetes mellitus. Clinical observation and literature study have found that it have a good effect on diabeties and complications, howerer, the mechanism research of Total glucosides from Cornus officinalis (TGCO) is exiguous. In this study, we intend to study the intervention effect and its protection mechanisms of TGCO on DM rats.Objective To study the intervention effect and its protection mechanisms of TGCO on diabetic cardiomyopathy, to provide experimental basis for popularization and application of Fructus Corni.Mechods Orthogonal design was used to optimize the extraction technology of total glucosides in Fructus Corni. Male Sprague Dawley rat was i.v administrated by streptozotocin (STZ) at a single dose of of 35 mg/kg to induce diabetic mellitus. On the 28th day, animals with serum glucose level more than 16.7 mmol/L were selected and divided into three groups:control, diabetic, diabetic+TGCO (18 mg/kg), administered 8 weeks from 5th to 12th week. During the experiment, we regularly recorded general condition of all the rats, such as weight, food intake, water intake and detected fasting blood glucose. At the end of the experiment, rats were weighted and anesthetized, and then the right carotid artery was cannulated with a BL-420S biological function of experimental system for recording of arterial pressure. Myocardial superoxide dismutase (SOD), malondialdehyde (MDA) and hydroxyproline of content was detected by kits. The pathological changes in heart tissue of the diabetic rats were observed by HE and MASSON staining methods. The protein expression of MMP-2、MMP-9、TIMP-1、TIMP-2、TGF-β1 and collagenⅣin cardiac tissue were detected by immunohistochemical method. Cardial myocyte was cultured under high glucose, MTT test was used to investigate the livability of high glucose incubated cardial myocyte.Results1. The best extraction condition of TGCO was material-liquid rate 25 mL/g, irradiation time 60 s,55% microwave and 45% light-wave ratio,70% alcohol concentration, which will receive total glucosides extract rate by 3.62 mg/g.2. Intervenous injection of STZ by tail creat T1-DM model rats, which has characteristic of excessive drink, excessive food, excessive urine, weight losing and glycemia.3. TGCO can greatly improve hemodynamics, protect cardial function of DM rats. 4. Biochemical results shows TGCO can reduce oxidative stress reaction of DCM rats’myocardial tissue.5. Immunohistochemical results indicates the expression of MMP-2 and MMP-9 were significantly reduced by treated with TGCO, while the expression of TIMP-1 and TIMP-2 increased, which shows TGCO can improve cardial reconstruction.6. MTT results shows that treatment with 1.0 mg/mL TGCO can significantly improve livability of cardial myocyte incubated with high glucose.Conclusion 1. Diabetes cardiomyopathy is affinity with overexpression of MMP-2/-9 and hyperoxidative state.2. Experiment proved that TGCO alleviated diabetic cardiomyopathy and improve cardial function effectively. The protect mechanism is possibly concerned with ameliorating the umbalance of extracellular matrix and anti-oxidative in cardial tissue.

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