川芎嗪对新生链脲佐菌素糖尿病大鼠大脑皮层胰岛素样生长因子1受体及凋亡相关蛋白表达的影响

Effects of Tetramethylpyrazine on Expressions of Insulin-like Growth Factor-1 Receptor and Apoptosis-related Proteins in Cerebral Cortex of Neonatal Streptozotocininduced Diabetic Rats

目的研究川芎嗪治疗对新生链脲佐菌素糖尿病大鼠大脑皮层形态结构及胰岛素样生长因子1受体、凋亡相关蛋白表达的影响。方法出生当日Wistar大鼠,一次性腹腔内注射链脲佐菌素制备新生链脲佐菌素糖尿病大鼠模型,设立对照组、模型组、川芎嗪组及二甲双胍组。第32周检测空腹血糖、空腹血浆胰岛素、胰岛素抵抗指数,观察大脑皮层病理组织学及超微结构改变,测定皮层组织中诱导型一氧化氮合酶活性、一氧化氮浓度及胰岛素样生长因子1受体、Bcl-2、Fas、Caspase-3的蛋白表达。结果川芎嗪治疗可以降低空腹血糖、空腹血浆胰岛素及胰岛素抵抗指数(P<0.01),可以改善大脑皮层光镜下及超微结构改变,抑制大脑皮层诱导型一氧化氮合酶活性(P<0.01)、降低NO浓度(P<0.01),可以增加大脑皮层胰岛素样生长因子1受体和Bcl-2蛋白表达(P<0.01),降低Fas(P<0.05)和Caspase-3蛋白表达(P<0.01)。结论川芎嗪可以通过多种途径发挥对糖尿病大鼠大脑皮层损伤的保护作用。

Aim To investigate the effects of tetramethylpyrazine on expressions of insulin-like growth factor-1 receptor（IGF-1R） and apoptosis-related proteins in cerebral cortex of neonatal streptozotocin（STZ）-induced diabetic rats.Methods Neonatal Wistar rats were intraperitoneally injected with a single dose of STZ to establish neonatal STZ-induced diabetic rat model.The neonatal rats were divided into 4 groups： normal control group,model group,metformin treatment group and tetramethylpyrazine treatment group.Fasting plasma glucose（FPG）,fasting insulin（FINS） and insulin resistance index（IRI） were measured at the 32 nd week.The changes of the cerebral cortex structure were observed with light microscope and electron microscope.Inducible nitric oxide synthase（iNOS） activity,nitric oxide（NO） concentration,and protein expression levels of IGF-1R,Bcl-2,Fas,and Caspase-3 in cerebral cortex were also analyzed.Results Tetramethylpyrazine not only attenuated the increases in FPG,FINS and IRI（P〈0.01）,but also ameliorated the changes of cerebral cortex structure.It inhibited i NOS activity（P〈0.01） and reduced NO concentration（P〈0.01） in the rat cortex.In addition,tetramethylpyrazine enhanced the impaired Bcl-2（P〈0.01） and IGF-1R（P〈0.01） expressions and decreased the expression levels of Fas（P〈0.05） and Caspase-3（P〈0.01） in cerebral cortex.Conclusion Tetramethylpyrazine ameliorates cerebral cortex injury in neonatal STZ-induced diabetic rats in multiple ways.