吡格列酮对高脂饮食大鼠胸主动脉PPARγ-核因子-κB途径的影响

Effects of pioglitazone on the thoracic aorta PPARγ-NF-κB pathway in hyperlipemic rats

目的观察吡格列酮对高脂饮食大鼠胸主动壁脉过氧化物酶增殖体激活受体(PPAR)γ mRNA表达及核因子(NF)-κB活性影响。方法雄性SD大鼠24只,随机分为3组:基础组(C)、高脂组(HL)、吡格列酮组(PI),每组8只。基础组饲基础饲料,其他两组饲高脂饲料。在饲喂饲料的同时,各组灌胃给相应干预剂。在0、3、6周尾静脉采血,测甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)水平。6周末留取胸主动脉组织。酶法测TG、TC、HDL-C水平,反转录聚合酶链反应(RT-PCR)测PPARγ mRNA表达,电泳迁移率变动分析(EMSA)测NF-κB活性。结果①HL组与C组相比,血清TG、TC含量明显升高(P<0.05),PI组较HL组明显降低(P<0.05),PI组与C组间差异无统计学意义。②HL组胸主动脉壁PPARγ mRNA表达较C组降低(P<0.05),NF-κB活性明显升高。③PI组主动脉壁PPARγ mRNA表达较HL组明显升高(P<0.05),NF-κB活性明显降低。结论吡格列酮具有降低血清TG、TC的作用;吡格列酮能通过上调高脂状态下大鼠胸主动脉壁PPARγ mRNA表达,抑制NF-κB激活。

Objective To explore the effects of pioglitazone on the expressions of PPARγmRNA and on the activities of NF-κB in thoracic aorta of hyperlipemic rats. Methods Twenty-four male Sprague-Dawley rats were randomized into three groups： the control group （group C）, the hyperlipemic group （group HL）, the pioglitazone group （group PI）, 8 rats in each. While the control group received normal diet only, the other two groups were put on high fat diet plus either 10 mg/kg body weight pioglitazone （group PI） or distilled water by gavage daily （group HL） till the end of the experiment. At weeks 0, 3 and 6, blood samples were collected from vena caudalis of these rats. After 6 weeks, the rats were sacrificed and harvested for thoracic aorta. The levels of serum TG, TC and HDL-C were tested by enzyme kits, PPARγ mRNA were measured by RT-PCR and the activity of NF-κB was determined using EMSA. Results ①The levels of serum TG and TC were higher in group HL than in group C （Γ〈0.05）, lower in grouo PI than in group HL （P〈0.05） but not statistically different between the groups PI and C. ②Compared with group C, group HL showed less expression of PPARγ mRNA （P〈0.05） and higher activity of NF-κB. ②Compared with group HL, group PI showed higher level of PPARγ mRNA and lower activities of NF-κB （P〈0.05）. Conclusion Reduced levels of TG and TC due to Pioglitazone treatment was Shown. Also, Pioglitazone appeared to inhibit activation of NF-κB by upregulating the expression of PPARγ mRNA in thoracic aorta of hyperlipemic rats.