NF-κB导致高脂饲养大鼠大血管病变  

The high fat-feeding induces macrovascular disease through activation of NF-κB in rat

作　　者：肖彧君[1] 母义明[1] 潘长玉[1] 柳红芳[1] 詹晓蓉[1] 李明[1] 陆祖谦[1] 陆菊明[1] 

机构地区：[1]解放军总医院内分泌科

出　　处：《中国糖尿病杂志》2006年第1期56-59,共4页Chinese Journal of Diabetes

摘　　要：目的探讨核因子-κB(NFκ-B)在高脂诱发的胰岛素抵抗中大鼠血管内皮细胞损伤的可能机制。方法45只Wistar雄性大鼠随机分为对照(NC)、高脂饲养(HF)和抗氧化剂N-乙酰半胱氨酸干预(HF+NAC)3组,饲养11周测定血糖、胰岛素、血脂以及体重的变化,处死大鼠,测定内脏脂肪含量、主动脉组织形态学改变,并用免疫组织化学法测定主动脉血管内皮细胞的细胞黏附分子1(ICAM-1)、单核细胞趋化蛋白1(MCP-1)和核因子-κB(NFκ-B)/IκBα的蛋白表达。结果(1)HF组大鼠11周后体重明显增加,血糖、胰岛素、TG、TC、LDL-C、FFA水平以及内脏脂肪占体重百分比均较NC组明显升高。NAC干预组则与NC组无明显差异;(2)HF组与NC和NAC组相比,表现为主动脉内膜不完整、断裂、内皮细胞脱落、内膜下泡沫细胞增多、炎细胞浸润、中层平滑肌增生、排列紊乱等;(3)HF组大鼠的主动脉内膜NF-κB为阳性表达、IκBα几乎不表达、ICAM-1和MCP-1呈强阳性表达,而NC组和NAC组NFκ-B为弱阳性表达、IκBα为阳性表达、MCP-1和ICAM-1均为阴性或弱阳性表达。结论高脂饲养大鼠可能通过激活NFκ-B导致大血管病变,抗氧化剂NAC能有效阻断高脂饲养大鼠的大血管病变。Objective To investigate the mechanism of endothelial cell damage under insulin resistance state induced by high fat-feeding by observations of the effects of antioxidant N-acetylcysteine （NAC） on the blood glucose, lipids, the histological parameters of aorta, and the expression of intercellular adhesion molecules-1 （ICAM-1）, monocyte chemoattractant protein 1 （ MCP-1 ） and NF-κB/ IκBα in aortic intima. Methods Forty-five Wistar male rats aged 5 to 6 weeks were randomly divided into 3 groups：control, high fat-feeding（HF） and HF plus NAC treatment（HF＋NAC）. Blood glucose, insulin, lipids, body weight, visceral fat content, histological change of aorta and the expression levels of ICAM-1, MCP-1 and NF-κB/IκBα were determined after the rats were fed for 11 weeks. Results （1）The body weight, ratio of visceral fat content over body weight, blood glucose, insulin, triglyceride, total cholesterol, LDL-C, and total FFA were significantly increased in HF group after 11 weeks feeding compared with control or HF＋NAC（all P〈0.01）;（2） A break in aortic intima integrity, exfoliation of endothelial cell, increase of foam cell number and infiltration of inflammatory cell were observed in HF group, while there were not these changes in both control and HF＋NAC groups; （3）A high expression levels of NF-κB, ICAM-1 and MCP-1, and little expression of IκBα were detected in aortic tunica intima in HF group, while little or no expression of NF-κB, ICAM-1 and MCP-1, and a high expression level of IκBα were detected in aortic tunica intima in control and HF＋ NAC groups. Conclusions High fat feeding induces macrovascular disease possibly through activation of NF-κB in rat, while antioxidant and NAC effectively prevent the macrovascular diseases in rat fed with high fat.

关 键 词：脂肪酸 胰岛素抵抗 血管病变 核因子-ΚB 

分 类 号：R587.2[医药卫生—内分泌]