石榴花多酚对糖尿病合并脂肪肝大鼠肝脏中PON表达的影响

Effects of pomegranate flowers polyphenols on liver PON expression of diabetes combining non-alcoholic fat liver diseases rats

探讨石榴花多酚对糖尿病合并脂肪肝大鼠肝脏的影响及作用机制。采用高脂喂养联合腹腔注射链脲佐菌素(streptozocin,STZ)的方法建立糖尿病合并脂肪肝大鼠模型,将成模大鼠随机分为:模型组、二甲双胍组、石榴花多酚低、中、高剂量组(75、150和300 mg.kg 1)。干预4周后处死大鼠,取血和肝脏,测定血清空腹血糖(fasting plasma glucose,FPG)、血脂、胰岛素水平(fasting insulin,FINS)和血清丙氨酸氨基转移酶(alanineaminotransferase,ALT)和天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平;肝脏及血清超氧化物歧化酶(superoxide dismutase,SOD)和丙二醛(malondialdehyde,MDA)含量;肝脏组织对氧磷酶(paraoxonase,PON1和3)mRNA和蛋白表达,并观察肝脏的病理改变。石榴花多酚各剂量组大鼠血脂、胰岛素抵抗水平和转氨酶显著降低;血清高密度脂蛋白胆固醇含量升高;肝细胞内脂肪滴较模型组明显减少;抗氧化能力增强;肝组织PON1 mRNA和蛋白表达水平显著增加。石榴花多酚可能通过增加肝组织中PON1 mRNA和蛋白的表达,缓解胰岛素抵抗,增强机体抗氧化能力从而改善大鼠肝脏脂肪变性。

To investigate the protective effects and possible mechanism of pomegranate flowers polyphenols（PFP） on liver function of rats with diabetes combining non-alcoholic fat liver diseases,diabetes combining nonalcoholic fat liver disease model rats were established with high calorie feeding and small dose intraperitoneal injection of streptozotocin（STZ）.Model rats were randomly divided into： model group,metformin group,pomegranate flowers polyphenols low,medium and high dose group（75,150 and 300 mg.kg 1）.After four weeks treatment,the levels of FPG,blood fat profiles and serum insulin,ALT,AST levels,SOD and MDA in the liver and serum separately were analyzed with biochemical methods.Paraoxonase（PON1 and PON3） mRNA and protein expression in liver were checked by RT-PCR and immunohistochemical method.Pathological changes of the liver were observed.FPG,IRI,non-HDL-C and transaminase significantly reduced and HDL-C raised in the each PFP dose group;Furthermore,compared with model group,fat drops in liver cells significantly reduced,antioxidant ability enhanced,PON1 mRNA and protein expression level in liver increased significantly.The protective effects of PFP against diabetes combining non-alcoholic fat liver diseases rats might through the increase liver PON1 mRNA and protein expression further enhanced the body antioxidant capacity and reduced IRI so as to ameliorate the rat hepatic steatosis.