川芎嗪与氨基胍对实验性胰岛素抵抗大鼠糖代谢的影响

Effect of Tetromethylpragine and Aminoguanidine on metabolism of glucose in insulin resistance rats

目的探讨川芎嗪与氨基胍对高糖胰岛素抵抗大鼠诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）和糖代谢的影响。方法雄性Wistar大鼠50只，随机分为正常对照组（NC）、高糖对照组（FC）、氨基胍组（AG）、川芎嗪组（TMP）、川芎嗪与氨基胍联合治疗组（AT），每组10只，均普通饲料喂养，高糖对照和各治疗组饮用12％果糖水复制高果糖胰岛素抵抗模型。摄入高糖3个月后，AG组给予氨基胍50mg／（kg·d）、TMP组给予川芎嗪40mg／（kg·d）、AT组给予川芎嗪40mg／（kg·d）与氨基胍50mg／（kg·d）灌胃治疗6个月。于实验前、实验中1、2、3、5、7、9个月末分别取尾静脉空腹血，测定血糖、血浆胰岛素、胰岛素敏感指数、血浆一氧化氮代谢物（NO2^-）、外周血白细胞iNOS mRNA表达。结果FC组与NC组比较，造模2个月，血浆NO2^-含量、外周血白细胞iNOS mRNA表达明显升高（P〈0．01），并持续保持在高水平上。造模3个月，动物血糖与血浆胰岛素水平升高，胰岛素敏感指数显著降低（P〈0．01）；AT治疗4-6个月，与FC组比较，血糖浓度降低，胰岛素敏感指数升高（P〈0．05）；血浆NO2^-含量、外周血白细胞iNOS mRNA阳性表达率降低（P〈0．01）。结论川芎嗪与氨基胍联合应用有抑制iNOS mRNA表达和缓解胰岛素抵抗作用。

Objective To study the effects of tetromethylpragine and aminoguanidine for the metabolism of glucose and the expressions of inducible nitric oxide synthase mRNA（iNOS mRNA） in expemnental insulin resistance rats. Methods Fifty male Wistar rats were randomly divided into the NC, FC, AG, TMP, and AT groups. The FC, AG, TMP and AT groups were fed with 12% fructose, and the NC group was fed with tap water. After 3 months, the AG group was treated with 50 mg/（kg·d） anfinoguanidine, the TMP group with 40 mg/（kg·d） tetromethylpmgine, and the AT group with 40 mg/（kg·d） tetromethylpragine and 50 mg/（kg·d） aminoguanidine for 6 months. The levels of blood sugar, insulin, NO2^- and the expression of iNOS mRNA were determined before the experiment and at the end of the 1^st, 2^nd, 3^nd, 5^th, 7^th and 9^th month. Results The level of blood NO2^- （ P 〈0.01） and the expression of the iNOS mRNA （ P 〈 0.01） were increased in the fructose control group compared with the control group and they remained at a high level till the end of 2 months＇ fructose intake. The plasma insulin and the blood glucose were both increased, and the insulin sensitivity index was significantly decreased in the fructose control group compared with the control group（ P 〈 0.01 ） at the end of 3 months＇ fructose intake. The blood glucose was decreased（ P 〈 0.05 ）, the insulin sensitivity index was increased （ P 〈 0.05）, and the NO2^- and the iNOS mRNA were decreased（ P 〈 0.01 ） at the end of 4 months＇ treatment with tetromethylpragine and aminoguanidine. Conclusion Tetromethylpraglne and aminoguanidine can inhibit the expression of the iNOS mRNA and improve insulin resistance in experimental mrs of fructose-induced insulin resistance.