吡格列酮对高脂血症大鼠血管内皮功能的保护作用

目的： 用1种PPARγ激动剂吡格列酮，观察其能否逆转高脂血症大鼠的内皮功能障碍。方法: 将36只健康雄性Wistar大鼠随机分为6组（每组6只）：正常对照组（control），高脂血症组（HC，即溶剂对照组）及吡格列酮1.5 mg·kg^-1·d^-1组、3 mg·kg-1·d-1组、10 mg·kg^-1·d^-1组、20 mg·kg^-1·d^-1组（HC＋PIO）。通过比较给予累积浓度的ACh（内皮依赖性舒血管物质）和酸化NaNO₂（非内皮依赖性舒血管物质）后血管的舒张程度来反映血管内皮功能；使用MS2000生理信号记录分析系统记录的参数（包括±dp/dt_max）来判定心脏功能。结果: （1）高脂血症可以导致严重的血管内皮舒张功能障碍，给予10^-9-10^-5 mol/L累积浓度的ACh后，高脂血症组血管张力与正常对照组相比有显著差异，血管最大舒张程度由99.78%±3.01%降低到50.51%±2.45%（P<0.01），而给予10^-8-10^-4 mol/L累积浓度的酸化NaNO₂后，2组间的血管张力无明显差别（P>0.05）；（2）吡格列酮可以剂量依赖性地减轻高脂血症引起的血管内皮舒张功能失调，且10 mg·kg^-1·d^-1剂量组作用最明显；（3）吡格列酮在减轻血管内皮舒张功能障碍的同时，也减轻了高脂血症大鼠心功能的损伤。结论: 吡格列酮可以直接减轻高脂血症引起的血管内皮功能障碍，从而可能会有效预防随后发生的动脉粥样硬化及缺血性心脏病。

Protective effects of pioglitazone on endothelial function in rats with hypercholesterolemia

AIM: To investigate the effects of pioglitazone,a PPARγ agonist,on endothelial cell (EC) dysfunction in hypercholesterolemic rats.METHODS: 36 healthy male Wistar rats were assigned to one of the following groups randomly (six rats in each group): control,hypercholesterolemia (HC),and HC treated with pioglitazone 1.5 mg·kg^-1·d^-1,3 mg·kg^-1·d^-1,10 mg·kg^-1·d^-1 and 20 mg·kg^-1·d^-1 (HC＋PIO),respectively.EC function was determined by comparing vasorelaxation to ACh,an EC dependent vasodilator,and acidified NaNO₂,an EC-independent vasodilator.Maximal positive and negative values of the instantaneous first derivative of LVP (+dp/dt_max and dp/dt_max) were determined by MS2000 system.RESULTS: (1) Hypercholesterolemia caused a significant endothelial diastolic dysfunction (maximal relaxation to ACh: 50.51%±2.45% vs 99.78%±3.01% in control,P<0.01).(2) Treatment with pioglitazone relieved EC-dependent vasodilatation in a dose dependent manner,and 10 mg·kg^-1·d^-1 is the best dose.(3) Pioglitazone not only improved EC function,but also reduced cardiac functional injury induced by hypercholesterolemia.CONCLUSION: EC dysfunction induced by hypercholesterolemia can be directly extenuated by pioglitazone,which may effectively prevent from subsequent atherosclerosis and ischemic heart disease.