Experimental Study Of The Influence On GK Mice Toll Like Receptor 4 Of Atorvastatin And Dimethylbiguanide

ObjectiveObserve the level of Toll like receptor 4 expressed in the blood plasm, myocardium and aorta thoracalis of the spontaneous GK mice and the change of the level of Toll like receptor 4 after using atorvastatin and dimethylbiguanide.Oberserve the index of the cardiac function and the blood vessel endothelial function of the GK mice and the change of the index of the cardiac function and the blood vessel endothelial function of the GK mice after using atorvastatin and dimethylbiguanide. Analysis the relationship of the level of Toll like receptor 4 expressed in the blood plasm of the spontaneous GK mice and the index the blood vessel endothelial function, preliminary to approach the control mechanisms of Toll like receptor 4 on metabolism of blood glucose and the influence on cardiovascular system and glycometabolism of Toll like receptor 4.MethodsThirty-two healthy adult GK mice were randomly divided into four groups:Experimental control group,eight GK mice are fed by distilled water; Atorvastatin group,eight GK mice are fed by atorvastatin(50mg/kg/d); Dimethylbiguanide group,eight GK mice are fed by dimethylbiguanide(100mg/kg/d); Combination group,eight GK mice are fed by atorvastatin(50mg/kg/d) and dimethylbiguanide(100mg/kg/d).Eight Wistar mice were served as Control group fed by distilled water.The blood pressure,the body weight and the blood glucose of the each group of the mice are detected once a week.After five weeks,hemodynamic results of each group of mice in the state of anesthesia with 3%sodium pentobarbital 30mg/kg are detected by application of multi-channel polygraph.Detect the blood glucose,insulin,endothelin,nitricoxide synthase(NOS),leptin(LEP),tumor necrosis factor(TNF)and Toll like receptor 4(TLR4) in the blood plasm of each group of mice.Toll like receptor 4 was detected in left ventricular myocyte and aorta thoracalis of the spontaneous GK mice and wistar mice by using immunohistochemistry method, PT-PCR and Western blot method.Oberserve the ultramicrostructure of left ventricular myocyte and aorta thoracalis of the spontaneous GK mice and wistar mice under the electron microscope.ResultsThe level of Toll like receptor 4 expressed in the blood plasm,myocardium and aorta thoracalis of the experimental control group mice is higher than that of the control group mice(P＜0.5).And the level of Toll like receptor 4 expressed in atorvastatin group and dimethylbiguanide group are lower than that of the experimental control group mice and the microstructure of myocardium and aorta thoracalis is improved(P＜0.5). The level of Toll like receptor 4 expressed in each group mice is correlated with the level of blood glucose and a variety of inflammatory mesons.The level of Toll like receptor 4 expressed in each group mice is related with the the index of cardiac function and blood vessel endothelial function.ConclusionsThe level of Toll like receptor 4 expressed in the GK mice increased,and atherosclerosis and diabetic cardiomyopathy occured.The level of Toll like receptor 4 expressed in the plasma is relevant with the level of the inflammatory mesons.After using atorvastatin and dimethylbiguanide,the level of Toll like receptor 4 expressed in the GK mice decreased and the cardiac function and the blood vessel endothelial function improved.