长期高脂喂养大鼠胰岛功能改变与胰岛炎症反应有关  

Alteration of islet function in rats with long-term high-fat diet is related to inflammation in islets

作　　者：李新[1] 袁莉[1] 李进[1] 李海玲[1] 程梭梭[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院内分泌科,湖北武汉430022

出　　处：《中国病理生理杂志》2009年第5期949-954,共6页Chinese Journal of Pathophysiology

基　　金：湖北省自然科学基金资助项目(No.2005ABA158)

摘　　要：目的:观察长期高脂喂养诱导的胰岛素抵抗大鼠胰岛炎症反应水平,并探讨其与胰岛功能改变的关联及机制。方法:8周龄的Wistar大鼠随机分为正常对照组(NC,n=15)和高脂组(HF,n=15),分别给予普通饲料及高脂饲料喂养。24周后行高胰岛素正葡萄糖钳夹试验检测胰岛素敏感性,行静脉葡萄糖耐量试验(IVGTT)检测β细胞功能,以免疫组化法检测胰岛β细胞内胰岛素相对含量(IRC)以及胰岛内NF-κB与caspase-3的相对浓度,以TUNEL法检测胰岛内细胞凋亡水平,以RT-PCR法检测胰岛内胰岛素原(INS)及白细胞介素(IL)-1βmRNA的相对表达量。结果:HF组葡萄糖输注率(GIR)较NC组显著降低[(5.32±0.90)mg.kg-1.min-1vs(7.80±0.51)mg.kg-1.min-1,P<0.01];NC组葡萄糖负荷后胰岛素分泌高峰出现于第5min,而HF组延迟至第10min,且10-60min胰岛素曲线下面积(AUCI)较NC组增加了67.7%(P<0.01)。免疫组化显示,HF组IRC较NC组减少了25.6%,NF-κB、caspase-3相对含量及单位面积胰岛凋亡细胞数分别增加20.5%、19.1%及2.43倍(均P<0.01)。HF组胰岛IL-1βmRNA相对表达量较NC组增加了1.95倍(P<0.01),INSmRNA表达水平增加了12.0%(P<0.05)。结论:长期高脂喂养诱导的胰岛素抵抗大鼠胰岛存在炎症反应,可能通过NF-κB及其介导的凋亡信号通路,与早期胰岛结构及功能损害有关。AIM ： To investigate the inflammation in islets of rats with long - term high - fat diet, and its relationship with the alterations of islet function. METHODS ： Thirty male Wistar rats of 8 - week age were randomly divided into normal control group （ NC, n = 15） and high - fat diet group （ HF, n = 15 ）, which were given normal chow or high - fat diet respectively for 24 weeks. Insulin sensitivity and islet function were detected by hyperinsulinemic euglycemic clamp and intravenous glucose tolerance test （ IVGTT）, respectively. Pancreases were stained by immunohistochemistry technique to qualitatively and/or quantitatively analyze the relative content of insulin （ IRC）, NF -kB and caspase - 3 in islets. The apoptosis of islet cells was detected by TUNEL. The mRNA expression of insulin （INS） and interleukin - 113 （ IL - 113 ） in islets were detected by reverse transcription - polymerase chain reaction （ RT - PCR）. RESULTS ： Compared with NC group, the glucose infusion rate （GIR） in HF group was decreased obviously [ （7.80±0.51 ） mg·kg^-1·min^-1vs （5.32±0.90） mg·kg^-1·min^-1, P 〈0. 01 ]. The peak of insulin secretion in intravenous insulin releasing test in HF was at 10 min, whereas that in NC was at 5 min. Area under the insulin curve （AUCI） of 10 to 60 min in HF was higher than that in NC [ （164. 5 ±14.4） mIU·L^-1· min^-1 vs （98.1 ±17.0） mIU·L^-1· min^-1, P 〈0.01 ]. Immunohistochemistry showed that IRC in HF was reduced by 25.6% compared with that in NC group. The relative content of NF -kB and caspase -3 was increased by 20. 5% and 19. 1%, respectively. The number of apoptotic cells in unit islets area was increased by 2. 43 times （all P 〈0.01 ）. The relative expression of IL - 1β was increased by 1.95 times （P 〈0. 01 ）. The relative expression of INS was increased by 12.0% （P 〈 0.05 ）. CONCLUSION： The alteration of islet function in insu-lin resistance rats induced by long - term high - fat diet is related to inflammat

关 键 词：胰岛素抗药性 胰岛功能 炎症 细胞凋亡 

分 类 号：R363[医药卫生—病理学]