Correlation of liver lesion with the expressions of SREBP-1c and JNK in the rats with diabetic mellitus / 中华老年医学杂志

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 groupsdiabetesgroup(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.