Caspase-3在胰岛素抵抗及其干预组大鼠肾组织中的表达及意义  

The Expression and Significance of Caspase-3 in the Rat Renal Tissue of Insulin Resistance Group as Well as Treatment Groups

作　　者：王蔚琛[1,2] 窦橙云[1] 魏树珍[3] 李莉[1] 李瑞峰[1] 

机构地区：[1]山东大学医学院病理生理学教研室,山东省济南市250012 [2]滨州医学院病理生理学教研室,山东省烟台市264003 [3]济南市中心医院妇产科,山东省济南市250013

出　　处：《中国动脉硬化杂志》2011年第1期18-22,共5页Chinese Journal of Arteriosclerosis

基　　金：山东省自然科学基金资助项目(Y2006C27);山东省卫生厅资助项目(99CA1CAA11)

摘　　要：目的建立胰岛素抵抗模型并药物干预,观察Caspase-3在肾组织的表达,以探讨其表达与胰岛素抵抗程度的关系。方法出生当日Wistar大鼠,腹腔注射链脲佐菌素STZ(100 mg/kg)复制胰岛素抵抗模型。设立正常对照组、胰岛素抵抗组、二甲双胍治疗组及川芎嗪+氨基胍干预组(联合治疗组)。8周、32周末采血,测空腹血糖、空腹血浆胰岛素,计算胰岛素抵抗指数;32周末取一侧肾组织用4%多聚甲醛固定24 h,石蜡包埋,制作5μm切片,另一侧肾组织液氮速冻后,-80℃冰箱保存备用。免疫组织化学测定Caspase-3在各组大鼠肾组织中的表达,免疫印迹实验测定肾组织中Caspase-3含量。结果 (1)胰岛素抵抗指数变化,胰岛素抵抗组明显高于对照组(P<0.01),二甲双胍组与联合治疗组均明显低于胰岛素抵抗组(P<0.01),且联合治疗组低于二甲双胍组(P<0.05)(2)Caspase-3变化,胰岛素抵抗组明显高于对照组(P<0.01),二甲双胍组、联合治疗组均明显低于胰岛素抵抗组(P<0.01),且联合治疗组低于二甲双胍组(P<0.05)。结论链脲佐菌素可诱导当日出生的Wistar大鼠产生胰岛素抵抗;该模型肾组织Caspase-3表达增强,且其表达强度与胰岛素抵抗程度正相关;二甲双胍及川芎嗪+氨基胍均有缓解胰岛素抵抗作用,其作用机制与下调Caspase-3表达有关,且川芎嗪+氨基胍的效果优于二甲双胍。Aim To establish rat model of insulin resistance,then treated by related drugs and to observe the expression of Caspase-3 in renal tissue,which was to investigate the relationship between amount of expression of Caspase-3 and extent of insulin resistance. Methods The insulin resistant model of neonatal Wistar rats was induced by a single intraperitoneal injection of streptozotocin（STZ） at a dose of 100 mg/kg.The Wistar rats were divided into four groups,including： normal control（control group）,insulin resistance（IR group）,the metformin（metformin group） and the combinated treatment of tetramethylpyrazine and aminoguanidine（combinated treatment group）.The concentrations of fasting blood glucose（FPG）,fasting insulin（FIN） and insulin resistance index（IRI）were measured on the eighth and thirty-second week.At the end of thirty-second week,one kidney of each rat was localized for 24 hours using 4% paraformaldehyde,embedded in the paraffin and made into 5um section.Another one was quickly frozen by liquid nitrogen,then stored at-80℃.IHC and western-blot were respectively used to qualitatively and quantitatively evaluate expression of Caspase-3. Results （1） The insulin resistance index in IR group was significantly higher than in control group（P0.01）.metformin and combinated treatment groups were remarkably lower than IR group（P0.01）;and combinated treatment group was less than metformin group（P0.05）.（2）The alteration of Caspase-3： IR group was obviously higher than control group（P0.01）,metformin and combinated treatment groups were evidently lower than IR group（P0.01）,and combinated treatment group was lower than metformin group（P0.05）. Conclusion The method of intraperitoneal injection of Streptozotocin can induce insulin resistance in neonatal Wistar rats;In this induced model the concentration of Caspase-3 increased,and there is a positive correlation between up-regulation of Caspase-3 and insulin resistance;metformin and the combined treatment with

关 键 词：胰岛素抵抗 WISTAR大鼠 CASPASE-3 

分 类 号：R363[医药卫生—病理学]