ABSTRACT
Objective To study the dynamic changes of injury and apoptosis of liver induced by lipid metabolic disturbance in the rats with diabetes mellitus and their correlation with the expressions of sterol regulatory element binding protein-1c(SREBP-1c)and c-Jun N-terminal kinase(JNK).Methods Experimental animals were randomly divided into 4 groups:diabetesgroup(n=64)induced by high-carbohydrate and high-fat diet plus intra-peritoneal streptozeotocin(STZ)injection,normal control(n=37)fed regular diet and receiving citric buffer solution injection,STZ group(n=42)fed regular diet and receiving STZ injection,high gluaxeard fat group(n =37)receiving citric buffer solution injection.Body weight,liver weight,fasting plasma glucose(FPG),fasting insulin(FINS),triglyceride(TG),total cholesterole(TC),alanine transaminase(ALT),asparate transaminase(AST)were detected at various time intervals.The changes of liver histopathology and ultrastructure were observed by ES and Sudan Ⅲ stanings,transmission electrom microscope.The expressions of SREBP-1c and JNK mRNAs and proteins were determined by real time-PCR methods.Apoptosis was analyzed by flow cytometry.Results The diabetic rats showed much lower body weight(P＜0.05)and higher liver weight than controls,STZ group and high-carbohydrate and fat group(P＜0.05),while showed higher levels(P＜0.05)of serum FPG,FINS,TG,TC,ALT,AST.Diabetic rats exhibited fatty degeneration of liver cells accompanied by inflammatory infiltration and fibrosis.Organelle structures were more disturbed and apoptosis was more obviou along with longer course of disease.The expressions of SREBP-1c,JNK proteins and mRNA were significantly enhanced.The rats fed high-carbohydrate and fat diet also showed similar liver lesions and enhanced SREBP-1c,J NK proteins and mRNA expressions but not as severe as in diabetes group Conclusions Insulin resistance and high blood glucose may induce diabetic hepatopathy.The high expressions of JNK and SREBP-1c may play important roles in liver lipid metabolism disorders and cell apoptosis.
ABSTRACT
Objective To study the roles of abnormal expressions of Caspase-8 and protein kinase C(PKC)-β of cardiomyocytes in the development of the apoptosis of cardiomyocyte in diabetic rat. Methods Rats were divided into 4 groups:(1)normal control (NC, n=37),(2)rats given STZ injection and normal diet(STZ,n= 42), (3) rats fed with high fat and high sngar ( HFS, n= 37), (4)rats given STZ injection and high fat and high sugar diet (type 2 DM, n=64). Plasma glucose, insulin and lipids were detected. At the end of experiment, the animals were sacrificed, and their hearts were examined. Pathological changes were observed and the expressions of Caspase-8, PKC-β mRNA were determined by real time-PCR method; apoptosis was analyzed by flow cytometry. Results (1)The body weight was higher in HFS group than in other three groups, and progressively decreased in type 2 diabetes group. The glucose level was highest in diabetic group, and was similar between groups of HFS and NC. (2)The apoptosis showed tendency to ascend during course of disease in diabetes model group. (3)The expressions of Caspase-8 and PKC-β mRNA were significantly enhanced in diabetes model group than in normal control group, and had a tendency to ascend during the course of disease.(4)The myocardial cells of the diabetic rats were rarified and swelling, fibrosis was observed. (5)At the 16th week, the level of plasma glucose was correlated positively with the expressions of Caspase-8 and PKC-β mRNA. Conclusions The enhancement of expressions of Caspase-8 amd PKC-β may play iportat rols in the pathogenesis of diabetic cardiomyopathy,in which apoptosis of the cardiomyocytes increased.
ABSTRACT
Objective To study the development of cardiomyopathy complicated with type 2 diabetes mellitus in the rats. Methods The 120 health male Sprague-Dawley rats, weighing 180-220 g, were divided into 4 groups: (1)STZ-modeled diabetes, fed with high-carbohydrate plus high-fat diet (n=40);(2)fed with regular diet (n=30);(3)and (4)SD rats with citrate buffer instead of STZ injection, fed with high-carbohydrate and high fat diet (n= 25);and fed with regular diet (n= 25); At the 4th, 8 th, 12 th and 16 th week after the intra-peritoneal injection of STZ solution or citrate buffer solution, rats from each group were scarified and examined. Results There were no significant differences in body mass and blood glucose among those groups after one week of feeding (P＞0. 05).After 4 weeks of feeding before injection, the body mass, fasting insulin (FINS) and insulin sensitive index (ISI) were obviously increased in diabetes group and high-carbohydrate plus high-fat control group as compared with STZ control group and normal control group (P＜ 0. 05). There were no significant differences between diabetes group and high-carbohydrate plus high-fat control group,between STZ control group and normal control group (P＞0. 05). After injection, the blood glucose,body mass, ventricular mass, TG and TC were higher in diabetes group and high-carbohydrate plus high-lipid control group than in STZ control group and normal control group (P＜0.05). The above parameters were much higher in diabetes group than in high-carbohydrate plus high-lipid control group, but there was no difference between STZ control group and normal control group (P＜0. 05).Pathological examination showed that the weight of the heart was significantly increased, the myocardial cells were hypertrophied accompanying degenerative changes and apoptosis, the interstitial collagen fibers were hyperplasia in the diabetic rats. The ultrastructures also presented severe damage.These changes indicated that cardiomyopathy was induced in the diabetes rats. Although similar changes were found in the rats fed with high-carbohydrate plus high-fat diet, they were much less significant than those in the diabetic rats. Conclusions Cardiomyopathy developes frequently in the rats with type 2 diabetes mellitus induced by feeding high-carbohydrate plus high-lipid diet and single intra-peritonial injection of 30 mg/kg STZ solution.