摘要
目的探讨固醇调控元件结合蛋白-1c(SREBP-1c)在胰岛素抵抗(IR)发病中的作用及罗格列酮(RSG)的干预机制。方法将27只大鼠适应性喂养1周后随机分为对照组、模型组及观察组各9只,模型组及观察组均予高脂饲料喂养8周建立IR模型,对照组予普通饲料喂养8周;其后观察组予RSG 3 mg/(kg.d)+生理盐水至2ml灌胃,模型组和对照组均予2 ml生理盐水灌胃。三组均同前喂养6周后取静脉血测定空腹胰岛素、空腹血糖、TG、游离脂肪酸(FFA)、TNF-α、瘦素,计算胰岛素敏感指数(ISI);处死动物后测定体脂比,取肝脏组织采用RT-PCR法检测SREBP-1c mRNA表达。同时对相关指标进行Pearson相关分析。结果SREBP-1c mRNA表达水平观察组为0.75±0.06、模型组为0.92±0.05、对照组为0.72±0.03,观察组及对照组均显著低于模型组,P均<0.01。Pearson相关分析显示,SREBP-1c mRNA与TG(r=0.802,P<0.01)、FFA(r=0.666,P<0.01)、TNF-α(r=0.749,P<0.01)、瘦素(r=0.708,P<0.01)、体脂比(r=0.495,P<0.01)均呈明显正相关,与ISI(r=-0.677,P<0.01)呈负相关。结论SREBP-1c mRNA过表达与IR发生有关,RSG可能通过降低SREBP-1c mRNA表达改善IR和脂代谢紊乱;此为IR及相关疾病的治疗提供了新的靶点。
Objective To investigate the role of sterol-regulatory element binding protein-1 c （SREBP-lc） in the occurrence of insulin resistance （IR） and the therapeutic mechanism of rosiglitazone（RGS）. Methods Twenty-seven rats were randomly divided intocontrol group, model group and observed group with 9 rats in each Model group and observed group were fed with high-fat diet for 8 weeks to establish IR model and , and the control group was fed with common diet for 8 weeks;then,the observed group was lavaged with 2 ml of RSG 3 mg/（ kg · d） in normal saline while other two groups were lavaged with 2 ml of normal saline. After all rats fed for another 6 weeks, the concentrations of fasting insulin, fasting glucose, triglyceride（TG）, free fatty acid （FFA） TNF-α and leptin in serum were measured, the insulin sensitivity index （ISI）was calculated; then the percentage of body fat （FAT%） was measured after the rats were sacrificed, and the SREBP-le mRNA expression in the liver was detected with RT-PCR. Pearson correlation was used to analysis the relationship betweenthe correlated indexes. Results The SREBP-1c mRNA expression level was 0.75 ± 0.06 in observed group, 0.92 ±0.05 in model group,0.72 ±0.03 in control group,which in the observed group and control group were both significantly lower than that in the model group,both P 〈 0.01. Pearson correlation indicated that SREBP-lc mRNA expression was significantly positive correlated with TG （ r = 0.802, P 〈 0.01 ）, FFA （ r = 0.666, P 〈 0.01 ）, TNF-α（ r = 0. 749, P 〈 0.01 ）, leptin （ r = 0.708, P 〈 0. 01 ）, FAT% （ r = 0.495, P 〈 0.01 ） but negative correlated with ISI （ r = - 0. 677, P 〈 0.01 ）. Conclusion Overexpression of SREBP-1c involved in the pathogenesis of IR, RSG can ameliorate IR and dyslipidemia by down-regulating the expression of SREBP-1c ;These provide new target for the treatment of insulin resistance and related diseases.
出处
《山东医药》
CAS
北大核心
2010年第23期39-41,共3页
Shandong Medical Journal
