苓桂术甘汤联合热量限摄对胰岛素抵抗模型大鼠的影响及机制研究

Effects of Linggui Zhugan Decoction Combined Calorie Restriction on the Insulin Resistance of Model Rats and Mechanisms Research

目的探讨苓桂术甘汤联合热量限摄对胰岛素抵抗(insulin resistance,IR)模型大鼠空腹血糖(FPG)、IR及过氧化物酶体增殖物激活受体-γ(peroxisome proliferator-activated receptor gamma,PPAR-γ)的影响。方法 48只雄性Wistar大鼠随机分为对照组、模型组、限摄组和中药限摄组,每组12只。对照组喂以普通饲料,其他3组以高脂饮食喂养12周建立IR模型。造模成功后,对照组和模型组继续原饲料喂养4天,并灌胃生理盐水20mL/(kg·d);限摄组给予热量限摄4天及生理盐水20mL/(kg·d)灌胃;中药限摄组给予热量限摄4天联合苓桂术甘汤20mL/(kg·d)灌胃。比较各组大鼠体重、FPG、血清空腹胰岛素(FINS)、胰岛素抵抗指数(IRI)和大网膜脂肪组织PPAR-γ蛋白表达。结果热量限摄4天后,与模型组比较,限摄组和中药限摄组大鼠体重明显下降(P<0.01),两限摄组间比较,差异无统计学意义(P>0.05);限摄组大鼠FINS、IRI明显降低(P<0.01,P<0.05),中药限摄组大鼠FPG、FINS和IRI均显著降低(P<0.05,P<0.01);两限摄组大鼠PPAR-γ蛋白表达均明显下降(P<0.01),痰湿状态均得到改善,以中药限摄组作用更显著。结论苓桂术甘汤联合热量限摄能降低IR模型大鼠体重、FPG及IRI,且较单纯热量限摄效果更佳,其改善IR作用可能与抑制PPAR-γ的活性有关,并可能同时具有抑制脂肪细胞分化的作用。

Objective To explore the effects of Linggui Zhugan Decoction （LZD） combined calorie restriction on fasting plasma glucose （FPG）, the insulin resistance （IR）, and the peroxisome proliferator- activated receptor γ, （PPAR-γ） of IR model rats. Methods Totally 48 male Wistar rats were randomly divid- ed into the control group, the model group, the calorie restriction group, and the TCM ＋calorie restriction group, 12 in each group. Ordinary forage was given to those in the control group, and high fat diet was fed to those in the rest 3 groups for 12 weeks to establish the IR model. After successful modeling, rats in the control group and the model group were continually fed with the original farage for 4 days. The normal saline at the daily dose of 20 mL/kg was given to them by gastrogavage. The normal saline at the daily dose of 20 mL/kg was given to rats in the calorie restriction group by gastrogavage after 4-day calorie restriction. LZD at the daily dose of 20 mL/kg was given to rats in the TCM ＋calorie restriction group by gastrogavage after 4-day calorie restriction. The body weight, FPG, serum fasting insulin （FINS）, insulin resistance index （IRI）, and the protein expression of PPAR-γ in the omental adipose tissue were compared. Results After 4-day calorie restriction, the body weight obviously decreased in the calorie restriction group and the TCM ＋calorie restriction group, when compared with the model group （P 〈0.01 ）. There was no statisticaldifference between the former two groups （P 〉0.05）. The FINS and IRI obviously decreased in the calorie restriction group （P 〈0.01, P 〈0.05）. The FPG, FINS, and IRI significantly decreased in the TCM ＋ calorie restriction group （P 〈0.05, P 〈0.01 ）. The protein expression of PPAR-γ obviously decreased in the calorie restriction group and the TCM ＋calorie restriction group （P 〈0.01 ）. The phlegm dampness state was allevi- ated, with more significant effects shown in the TCM ＋ calorie restriction group. Conclusions LZD com- bined calorie restriction could reduce the body weight, FPG, and IRI of IR rats. Besides, it showed better effects than calorie restriction alone. Its effects in improving IR might be correlated with inhibiting the activi- ties of PPAR-γ Meanwhile, it might play a role in inhibiting the differentiation of fat cells.