胰岛素治疗对糖尿病大鼠肝脏色素上皮衍生因子表达的影响

Effects of Insulin Therapy on Pigment Epithelium-Derived Factor(PEDF) Expression in Liver of Diabetic Rats

【目的】探讨胰岛素治疗改善2型糖尿病大鼠肝脏中色素上皮衍生因子(PEDF)的表达及其内在机制。【方法】8周龄雄性Spraque-Dawley大鼠高脂喂养联合小剂量链脲佐菌素诱导糖尿病模型(12只),按随机数字表法分3组为:糖尿病模型组(DM,6只)、胰岛素治疗组(INS,6只);另设正常对照组(N,6只)。通过Western blotting法检测大鼠肝脏PEDF、基质金属蛋白酶(MMP2)和肿瘤坏死因子-α(TNF-α)的蛋白表达。【结果】胰岛素治疗后降低了糖尿病大鼠空腹血糖及血清甘油三酯的含量,改善糖尿病大鼠肝脏脂质沉积的状态;糖尿病大鼠肝脏中TNF-α及MMP2的蛋白表达高于正常组(P<0.05),PEDF的蛋白表达低于正常组(P<0.05),胰岛素治疗后降低了糖尿病大鼠肝脏TNF-α及MMP2的表达,上调PEDF的表达。【结论】胰岛素对糖尿病大鼠肝脏PEDF的上调作用可能与胰岛素的抗炎作用有关,这也可能是胰岛素改善肝脏脂质沉积的机制之一。

[Objective] To investigate the expression of Pigment Epithelium-Derived Factor（PEDF） in liver of diabetic rats treated by insulin and underling mechanism.[Methods] High-fat diet and low dose streptozotocin（STZ）induced diabetic rats,which were randomly divided into 2 groups：diabetic rats（n=6）,diabetic rats treated with NPH insulin（n = 6）,with 6 normal animals as control.After three-week intervention,protein expressions of PEDF,tumor necrosis factor-α（TNF-α）,matrix metalloproteinase 2（MMP2） in liver were measured by Western blotting.[Results] Insulin decreased fasting blood glucose,serum triglycerides and liver triglycerides in diabetic rats.Significant lipid deposition was reversed in livers of diabetic rats treated by insulin.Compared to normal rats,untreated diabetic rats had higher TNF-α,MMP2 protein expressions and lower PEDF protein expression.The response to insulin therapy in diabetic rats showed downregulated protein expressions of TNF-α and MMP2,upregulated PEDF in liver.[Conclusion] The upregulation of PEDF protein expression by insulin may be responsible for the anti-inflammatory action of insulin,which maybe one of the mechanisms that insulin ameliorates triglycerides deposition in liver.