吡格列酮对高脂血症大鼠核转录因子кB活性和主动脉凋亡蛋白表达的影响  

Effect of pioglitazone on activity of NF-KB and expression of aorta apoptosis proteins in rats with hyperlipidemia

作　　者：李蓉[1] 蔡辉[2] 赵凌杰[2] 董晓蕾[2] 袁爱红[2] 

机构地区：[1]南方医科大学南京临床医学院,210002 [2]南京军区南京总医院中西医结合科

出　　处：《中华老年心脑血管病杂志》2012年第5期468-471,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：中国博士后科学基金(20090461491)

摘　　要：目的观察吡格列酮对高脂血症大鼠NF-κB活性和主动脉凋亡蛋白Bax、Bc1-2表达的影响。方法 SD大鼠26只,随机分为对照组9只、高脂饮食组17只。高脂饮食组喂养12周后再随机分为模型组8只和吡格列酮组9只,干预4周后,检测各组血脂;HE染色观察主动脉组织形态学改变;免疫组织化学法检测NF-κB p65、Bax、Bc1-2表达。结果与对照组比较,高脂饮食组12周后,TG、TC、LDLC明显升高(P<0.01);与模型组比较,16周后,吡格列酮组TG、TC明显降低(P<0.01);与对照组比较,模型组NF-κB p65、Bax明显升高,Bc1-2和Bc1-2/Bax比值明显降低(P<0.01);与模型组比较,吡格列酮组NF-κB p65、Bax明显降低,Bc1-2和Bc1-2/Bax比值明显升高(P<0.01)。结论高脂饮食可引起主动脉凋亡蛋白Bax、Bc1-2及Bc1-2/Bax比值的改变,可能与NF-κB活性增加相关。吡格列酮可减少NF-κB p65表达,调节Bax、Bc1-2表达,从而改善内皮细胞功能和动脉粥样硬化病理进程。Objective To observe the effect of pioglitazone on activity of NF-κB,Bax and Bcl-2 in rats with hyperlipidemia.Methods Twenty-six male SD rats were randomly divided into control group（n=9） and high fat diet group（n=17）.Rats in high fat diet group were further randomized into model group（n=8） and pioglitazone group（n=9） after fed with high fat diet for 12 weeks.Four weeks after intervention,serum lipid levels were measured and morphology of aortic tissue was observed with HE staining in different groups.Expressions of NF-κB p65,Bax and Bcl-2 in aortic tissue were analyzed by immunohistochemistry.Results The serum levels of lipid were significantly higher in high fat diet group after fed for 12 weeks（P〈0.01）.The serum levels of TG and TC were significantly lower in pioglitazone group than in model group with smooth and intact tunica intima of atorta and no significant proliferation of smooth muscle cells was found after fed for 16 weeks（P〈0.01）.The expression levels of NF-κB p65 and Bax were significantly higher in model group than in control group and significantly lower in pioglitazone group than in model group（P〈0.01）.The expression level of Bcl-2 and the ratio of Bcl-2 and Bax were significantly lower in pioglitazone group than in control group and significantly higher in pioglitazone group than in model group（P〈0.01）.Conclusion High fat diet can change the expression of Bax and Bcl-2 in aorta,which may be related with the increased NF-κB activity.Pioglitazone can downregulate the serum lipid level and the expression of NF-κB p65,and up-regulate the expression of Bax and Bcl-2,thus improving the function of endothelial cells and alleviating atherosclerosis.

关 键 词：高脂血症 NF-KB 动脉粥样硬化 内皮细胞 基因表达 

分 类 号：R589.2[医药卫生—内分泌]