吡格列酮能部分抑制2型糖尿病大鼠肝脏微粒体细胞色素P450活性

Effect of pioglitazone on liver microsome cytochrome P450 in diabetic rats

目的:探讨吡格列酮对糖尿病大鼠肝脏微粒体细胞色素P450 (CYP450)活性水平的影响。方法:40只大鼠随机均分为正常对照组、糖尿病组、低剂量(3 mg/kg)吡格列酮组、高剂量(6 mg/kg)吡格列酮组(n=10)。除正常对照组外,其余各组给予高脂饲料喂养4周,采用链脲佐菌素(50 mg/kg)腹腔注射建立糖尿病大鼠模型。造模成功后,低、高剂量吡格列酮组大鼠给予相应剂量吡格列酮灌胃治疗2周,提取大鼠肝脏微粒体并检测CYP450活性水平,同时进行大鼠体质量和血糖指标的检测。结果:与正常对照组相比,糖尿病组大鼠血糖升高(P<0.01),CYP450活性水平升高(P<0.05),体质量下降(P<0.01)。与糖尿病组相比,吡格列酮灌胃2周期间,大鼠血糖浓度随吡格列酮浓度升高显著降低(P<0.01),低、高剂量吡格列酮组大鼠肝微粒体CYP450水平均明显降低(P<0.01),体质量明显升高(P<0.05)。相关分析显示,CYP450活性水平与大鼠血糖正相关(r=0.598,P<0.01),而与大鼠体质量无明显相关性。结论:吡格列酮对糖尿病大鼠肝脏微粒体CYP450酶活性有显著抑制作用,能改善其高血糖状态,增加大鼠体质量。

Objective:To explore the effects of pioglitazone on the cytochrome P450 in the liver microsomes of the diabetic rats. Methods:Forty rats were randomly divided into four groups ( n =10 in each group): normal control group, diabetes model group, 3 mg/kg and 6 mg/kg pioglitazone groups. Except the normal control, all other groups were fed with high-fat diet for 4 weeks, and then diabetic model rats were established by intraperitoneal injection with streptozotocin (STZ) of 50 mg/kg once. After modeling, rats in the pioglitazone groups were continuously intragastric administrated with pioglitazone for 2 weeks, and then sacrificed and the liver microsomes were extracted for the assay of P450. Meanwhile, the blood glucose and body weight were measured. Results:Compared with the normal control, the blood glucose in the diabetes model group increased significantly ( P <0.01), the expression of cytochrome P450 also significantly increased ( P <0.05), and body weight significantly decreased ( P <0.01). Compared with the diabetes model group, during the 2 weeks of gavage, with the increasing of pioglitazone dose, the blood glucose in pioglitazone groups decreased remarkably ( P<0.01), and the expression of cytochrome P450 obviously decreased in the two pioglitazone groups ( P<0.01), whereas the body weight increased ( P<0.05). In addition, the correlation analysis showed that there was a significantly positive correlation between cytochrome P450 and blood glucose in rats and the correlation coefficient was 0.598 ( P<0.01). There was no significant correlation between cytochrome P450 and body weight in rats. Conclusions:Pioglitazone could inhibit the activity of cytochrome P450 in the liver of diabetic rats, reduce the blood glucose, and increase body weight in diabetic rats.