吡格列酮对高脂血症大鼠主动脉脂联素受体表达的影响

Influence of Pioglitazone on the Expression of Adipor on Aortic in Hyperlipidemia Rats

目的观察高脂血症大鼠主动脉脂联素受体(adiponectin receptors1/2,AdipoR1/2)的表达改变,探讨吡格列酮对高脂血症大鼠主动脉血管脂联素受体表达的影响。方法清洁级SD大鼠26只,随机分为正常饮食组(9只)和高脂饮食组(17只);高脂饮食组12周后检测空腹血脂,明确造模是否成功,随机分为模型组(8只)和吡格列酮组(9只),后者给予吡格列酮溶液(0.6mg/ml)连续灌胃4周,之后检测血脂水平及主动脉病理,ELISA法检测血清脂联素水平,荧光RT-PCR法检测主动脉脂联素受体AdipoR1和AdipoR2mRNA的表达,Western Bolt法检测脂联受体蛋白表达。结果高脂饲料喂养12周,高脂饮食组TG、TC、LDL水平明显升高(P<0.01);给药四周后,吡格列酮组TG、TC水平明显降低(P<0.01),模型组主动脉脂联素受体1/2mRNA和蛋白的表达明显下降(P<0.01)。与模型组比较,吡格列酮组主动脉AdipoR(1P<0.05)和AdipoR2(P<0.01)mRNA的表达明显升高,主动脉脂联素受体蛋白的表达明显升高(P<0.05),差异有统计学意义。结论脂联素及其受体下降可能介入高脂血症血管损伤,吡格列酮具有抗动脉粥样硬化作用,该作用可能与提高血清脂联素和主动脉血管脂联素受体表达有关。

Objective To observe the expression of AdipoR on the aorta in hyperlipidemia rats,and to investigate the influence of pioglitazone on the expression of AdipoR on aortic in hyperlipidemia rats,and the possible mechanism of anti-atherosclerosis.Methods 26 male SD rats were randomly divided into the high-fat diet group(17)and control group(9).high-fat diet group was fed with hypercholesterol diet for 12 weeks,then the serum lipid level was measured in the all rats,and to know whether the model of rats with hyperlipidemia was constructed by feeding hypercholesterol diet,then 17 male SD rats were randomly devided into two groups:model group,high hyperlipidemia with pioglitazone group.By intragastric administration,pioglitazone group rats were given pioglitazone(0.6mg/ml)for four weeks,then the serum lipid levels of all rats were measured and the aorta was taken for pathologic analysis.Serum adiponectin was detected by ELISA.AdipoR was measured by Western Bolt and reverse transcription polymerise chain reaction(RT-PCR).Results After 12 weeks of feeding,compared with control group,the high-fat diet group show significantly higher levels of total cholesterol(TC),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C)(P<0.01).After 4 weeks’ treatment,as compared with the model group,the level of TC,TG in the pioglitazone group was obviously lower(P< 0.01),the level serum of adiponectin was significantly increased(P<0.05),and the mRNA expression of both AdipoR1(P<0.05)and AdipoR2(P<0.01)were significantly increased,and the protein expression of both AdipoR1 and AdipoR2 were significantly increased(P<0.05).Conclusion Dcreased adiponectin and its receptors may be involved in vascular impairment in rats with high-fat diet induced hyperlipidemia.Pioglitazone has anti-atherosclerotic effect,the effect may be related to increased serum adiponectin and vascular expression of adiponectin receptor.