吡格列酮对高脂血症大鼠主动脉PPARγ-NF-kB的影响

Influence of pioglitazone on PPARγ-NF-kB expression of aorta in hyperlipidemia rat

目的观察吡格列酮对高脂血症大鼠主动壁过氧化物酶增殖体激活受体(PPAR)γ及核因子(NF)-kB表达的影响。方法清洁级SD大鼠26只,随机分为正常饮食组(对照组,9只)和高脂饮食组(17只);高脂饮食组喂以高脂饮食12周后检测空腹血脂,造模成功后,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,对照组和模型组给予等量蒸馏水灌胃4周。用药4周后检测各组血脂、主动脉病理、主动脉一氧化氮、一氧化氮合成酶水平,并通过免疫组织化学法检测PPARγ和NF-kB表达。结果高脂饲料喂养12周后造模成功。给药4周后,吡格列酮组TG、TC明显下降;与对照组比较,模型组主动脉NO、cNOS显著下降(P<0.01),吡格列酮可显著提高主动脉NO、cNOS(P<0.01);与模型组比较,吡格列酮组PPARγ表达明显升高(P<0.01),NF-kB表达明显下降(P<0.01)。结论吡格列酮具有降低血清TG、TC的作用,升高主动脉NO、cNOS水平;吡格列酮能提高主动脉PPARγ表达,抑制NF-kB表达。

Objective To explore the effects of pioglitazone on the expressions of PPARγ and NF-kB of aorta in hyperlipemic rats.Methods 26 male SD rats were randomly divided into two groups： the high-fat diet group（control group,n=17） and full diet group（n=9）.high-fat diet group were fed high-fat diet（HF） for 12 weeks,then serum lipid level was measured in the all rats,and when the hyperlipidemia model was estimated,the high-fat diet group rats were randomly divided into two groups： the model group,high-fat diet with Pioglitazone group.By intragastric administration,Pioglitazone group was given pioglitazone（0.6mg/ml）for four weeks,and control group and model group were given with tales doses of distilled water for four weeks.After 4 weeks＇ treatment,serum lipid level was measured in the rats.the aorta was taken for pathologic analysis.Serum levels of NO was detected,the level of NOS of aorta,the expression of PPARγ and NF-kB were detected by western bolt.Results After 12 weeks of feeding,the hyperlipidemia model was estimated.After 4 weeks,treatment,As Compared with model group,serum levels of TG,TC decreased significantly（P0.01）.The level of NO,cNOS in Pioglitazone group were significantly increased（P0.01）.The protein expression of PPARγ was significantly increased（P0.05）,but the protein expression of NF-kB was significantly inhibited.Conclusion Pioglitazone can effectively prevent vascular endothelium from impairment by restoring NO,cNOS,PPARγ concentration and down-regulale NF-kB expression in these rats.