TNF-α诱导的胰岛素抵抗对小鼠脂肪组织INSIG2和SCAP表达的影响  

Effects of TNF-α-mediated insulin resistance on INSIG2 and SCAP expressions in vivo

作　　者：孙滨[1] 李伶[1] 杨刚毅[2] 程玉兰[1] 朱伟[2] 孙逊[2] 

机构地区：[1]重庆医科大学医学检验系临床生化教研室和教育部重点实验室,重庆400016 [2]重庆医科大学附属第二医院内分泌科,重庆400016

出　　处：《中国病理生理杂志》2009年第5期929-933,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30771037;No.30871199);重庆市教委科研基金资助项目(No.KJ050304);重庆医科大学重点课题资助项目(No.XBZD200704)

摘　　要：目的:探讨肿瘤坏死因子α(TNF-α)诱导的胰岛素抵抗(IR)对脂代谢相关基因INSIG1、INSIG2、SCAP和SREBP表达的影响。方法:健康雄性C57BL/6J小鼠随机分为4组,分别给予腹腔注射TNF-α(6μg.kg-1.d-1、3μg.kg-1.d-1和1μg.kg-1.d-1)和生理盐水(NC组)每天2次,共7d。采用静脉葡萄糖耐量试验(IVGTT)评价小鼠胰岛素敏感性和糖代谢的变化,用酶法测定胆固醇、甘油三酯、游离脂肪酸等变化,用RT-PCR法检测脂肪组织胰岛素诱导基因1和2(INSIG1、INSIG2)、固醇调节元件结合蛋白裂解激活蛋白(SCAP)和固醇调节元件结合蛋白(SREBP)基因的RNA表达,并用Western blotting检测INSIG2蛋白的表达。结果:TNF-α处理后,小鼠空腹血糖(FBG)、血浆胰岛素和游离脂肪酸(FFA)水平均明显增高(P<0.01和P<0.05)。IVGTT结果显示,TNF-α(6μg.kg-1.d-1)组糖耐量低减,葡萄糖刺激后胰岛素释放水平明显高于其它3组。TNF-α(6μg.kg-1.d-1)组小鼠脂肪组织中INSIG2mRNA表达明显高于对照组(P<0.01),其蛋白水平也明显高于对照组(P<0.05)。TNF-α(6μg.kg-1.d-1)组小鼠脂肪组织SCAPmRNA表达也明显高于对照组(P<0.05)。两组小鼠脂肪组织INSIG1和SREPP1mRNA表达无明显差异(P<0.05)。结论:INSIG2和SCAP的变化可能与TNF-α所导致的脂代谢紊乱有关。AIM： To investigate the effects of TNF-α induced insulin resistance （IR） on INSIGI, INSIG2, SCAP and SREBP expressions in mice. METHODS： Male C57BL/6J mice were randomly divided into 4 groups. The mice were given an intraperitoneal injection of TNF-α （6 μg·kg^-1·d^-1; 3 μg·kg^-1·d^-1 and 1μg·kg^-1·d^-1） and saline （ NC group） twice daily for 7 d. The insulin sensitivity and glucose metabolism in awaken mice were evaluated by intravenous glucose tolerance test （IVGTF）. The mRNA expression and protein levels of gene were measured by RT - PCR and Western blotting. RESULTS： After TNF- α treatment, fasting blood glucose （FBG）, plasma insulin and free fatty acids （FFA） were significantly elevated in TNF-α （6 μg·kg^-1·d^-1） group compared to NC, TNF-α （1μg·kg^-1·d^-1） and TNF- α （3 μg·kg^-1·d^-1） groups （P 〈0. 01 and P 〈 0. 05, respectively）. There was a lower glucose tolerance in TNF - α （6μg·kg^-1·d^-1 ） group than that in other three groups during IVGTT. In TNF - α （6μg·kg^-1·d^-1 ） group, the insulin release of glucose - stimulation was higher than that in NC and TNF - α（ 1μg·kg^-1·d^-1 ） groups （ P 〈 0. 01 and P 〈 0. 05 ）. The INSIG2 mRNA expression of adipose tissues in TNF - α （6μg·kg^-1·d^-1 ） group was significantly increased compared with NC group （ P 〈 0. 01 ）, and INSIG2 protein levels were also increased （ P 〈 0. 05）. In TNF - α treatment mice, SCAP mRNA level in adipose tissues was significantly up - regulated than that in the controls （ P 〈 0. 05）. The mRNA expressions of INSIG1 and SREBP1 in two groups were not significantly changed （ P 〉 0. 05）. CONCLUSION： In TNF - α induced insulin resistance, INSIG2 and SCAP may be involved in the pathways of lipid metabolism.

关 键 词：肿瘤坏死因子 胰岛素抵抗 脂代谢紊乱 基因表达 

分 类 号：R363[医药卫生—病理学]