大剂量抗氧化剂对高脂饲养大鼠胰岛β细胞分泌功能的影响及机制  

N-acetyl-l-cysteine improves function of islet β cell in hyperlipidemic rats and its mechanism

作　　者：王冰[1] 李宏亮[1] 杨文英[1] 萧建中[1] 杜瑞琴[1] 白秀平[1] 潘琳[2] 

机构地区：[1]卫生部中日友好医院内分泌科,北京100029 [2]卫生部中日友好医院临床医学研究所内科实验室,北京100029

出　　处：《浙江大学学报（医学版）》2007年第6期575-580,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金资助(30640081)

摘　　要：目的:探讨大剂量抗氧化剂-N-乙酰半胱氨酸(N-acetyl-l-cysteine,NAC)对高脂饲养大鼠胰岛β细胞分泌功能的影响及可能机制。方法:将59只8周龄SD大鼠随机分为正常饲料组(NC组)、高脂饲料组(HF组)和高脂+NAC组(NAC组)。饲养20周,(1)测血浆及胰腺组织丙二醛(MDA)和还原型谷胱甘肽(GSH)水平;(2)正常血糖高胰岛素钳夹实验,评价外周组织胰岛素抵抗程度;(3)胰岛细胞表面灌注实验,评价离体胰岛β细胞动态分泌功能;(4)实时荧光定量PCR方法比较各组大鼠胰岛素受体底物-1(IRS-1)、胰岛素受体底物-2(IRS-2)和葡萄糖转运子-2(Glut-2)mRNA表达的变化。结果:(1)HF组血浆及胰腺MDA水平明显高于NC组,GSH水平低于NC组,NAC可以改善以上变化;(2)HF组葡萄糖输注率(GIR)比NC组降低(P<0.01),用NAC后GIR明显改善(P<0.01);HF组葡萄糖刺激的胰岛素分泌(GSIS)功能下降,用NAC后可逆转上述变化;(3)HF组胰岛细胞IRS-1、IRS-2、Glut-2mRNA表达降低42.3%、28.1%、22.9%(P均<0.05);NAC组胰岛细胞IRS-1、IRS-2、Glut-2 mRNA表达与HF组相比增加40.2%、30.2%,19.1%(P均<0.05)。结论:大剂量抗氧化干预治疗能改善胰岛细胞胰岛素信号传导,逆转高脂饲养导致的大鼠胰岛细胞分泌功能紊乱,其机制可能与NAC纠正机体氧化及抗氧化失衡有关。Objective： To investigate the effect of N-acetyl-l-cysteine （NAC） on islet β cell function in hyperlipidemic rats and its mechanism. Methods： Fifty-nine male SD rats of 8 week old were randomly divided into 3 groups：normal diet group （NC,n = 20）,high fat diet group （HF, n=20） and NAC treated group （NAC,n=19,NAC 300 mg· kg^- 1 · d^-1 and high fat diet）. At the end of 20 weeks, fasting serum insulin （Ins）,glucose （Glu）, malonaldehyde （MDA） and reduced glutathione （GSH） were determined in plasma and pancreas tissue. The glucose infusion rate （GIR） was measured by euglycemic hyperinsulinemia clamp to evaluate the peripheral insulin resistance. Pancreatic islets were isolated and subjected to a perifusion medium containing 3.3 mmol/L glucose for 15 min,followed by 16. 7 mmol/L glucose for 30 min,insulin content of perifusion medium was measured by RIA. The expressions of IRS-1,IRS-2,Glut-2 gene in islets were detected by real time PCR. Results： （1）The insulin,glucose and MDA concentration in HF group were higher than those in NC group,but GSH levels in plasma and pancreas were lower. NAC intervention could reverse these effects. （2）The GIR was decreased significantly in HF group compared with NC group [（5. 25±1.2） vs （13. 56±1.7）mg · min^-1 · kg^-1,p〈0. 011, NAC intervention reversed these effect：GIR [（9. 28±1.50） vs （5.25±1.2）mg · min^-1 · kg^-1,P 〈0. 011. （3） 16.7 mmol/L glucose increased the insulin secretion in the islet cells of the three groups,but the peak was lower in HF group. NAC intervention reversed these effects. （4） The gene expression of IRS-1 was significantly decreased by 42.3% in HF group （P〈0.05） ,and the expressions of IRS-2 and Glut-2 were decreased by 28. 1% and 22. 9% （P〈0. 05） compared with NC group. In contrast, the expressions of IRS-1, IRS-2, Glut-2 in NAC group increased by 40. 2% ,30. 2% and 19. 1%, respectively than those in HF group. Conclusion： NAC can reverse functional disorder o

关 键 词：乙酰半胱氨酸 胰岛/细胞学 胰岛素/分泌 N-乙酰半胱氨酸 胰岛β细胞 实时荧光定量PCR 

分 类 号：R587.1[医药卫生—内分泌]