不同降糖药物对2型糖尿病大鼠血浆及胃组织Ghrelin水平的影响

目的观察胰岛素、二甲双胍和吡格列酮对2型糖尿病大鼠血浆胃促生长素（ghrelin）及其在胃中表达水平的影响，探讨ghrelin与胰岛素敏感性的关系。方法采用高糖高脂饮食加小剂量链脲佐菌素建立2型糖尿病大鼠模型,成模大鼠随机分为糖尿病对照组（DC组）、胰岛素治疗组（INS组）、二甲双胍治疗组（MET组）和吡格列酮治疗组（PIO组）。干预8周，酶联免疫法检测血浆ghrelin水平，免疫组织化学法检测胃组织中ghrelin的表达水平。结果与DC组比较，INS组血浆及胃组织中ghrelin水平升高，但差异无统计学意义，MET组和PIO组血浆及胃组织中ghrelin均显著升高，差异均有统计学意义（P均＜0.01）。相关分析显示，DC、MET及PIO组血浆ghrelin与空腹胰岛素呈负相关（r分别为-0.427、-0.265、-0.362），与胰岛素敏感性（ISI）呈正相关（r分别为0.392、0.563、0.228）。多元线性回归分析表明，FINS、ISI与血浆ghrelin独立相关。结论二甲双胍和吡格列酮可升高2型糖尿病大鼠血浆及胃组织中ghrelin水平，改善胰岛素抵抗。

Effects of different anti-diabetic drugs on plasma ghrelin and expression of ghrelin in stomach tissues of type 2 diabetic rats

Objective To investigate the effects of insulin,metformin and pioglitazone on plasma ghrelin and the expression level of ghrelin in stomach tissues of type 2 diabetic rats and to explore the correlation between ghrelin and insulin sensitivity.Methods Type 2 diabetic rat model was established by feeding with high glucose and high fat diets and injecting a low dosage of streptozotocin(STZ).Then the diabetic rats were divided into four groups: the diabetic control group(DC),the insulin-treatment group(INS),the metformin-treatment group(MET) and the pioglitazone-treatment group(PIO).8 weeks later,the plasma ghrelin and the ghrelin expression levels in the stomach were determined by enzyme-linked immunoassay(EIA) and immunohistochemistry.Results The ghrelin levels of the plasma and stomach were increased in the INS group compared with the DC group,but the difference was not significant.The ghrelin levels of the plasma and stomach in the MET and PIO groups were significantly increased compared with the DC group(P<0.01).The plasma ghrelin level was negatively correlated with FINS,but positively with ISI in the DC,MET and PIO groups.Multiple linear regression analysis showed that FINS and ISI were independent factors for the plasma ghrelin level.Conclusion Metformin and pioglitazone can increase the ghrelin levels of the plasma and stomach tissues and the insulin sensitivity in type 2 diabetic rats.