利拉鲁肽对肥胖大鼠脂肪组织内质网应激的影响

Effects of Liraglutide on Endoplasmic Reticulum Stress of Fatty Tissue in Obese Rats

目的:研究利拉鲁肽对肥胖大鼠脂肪组织内质网应激的影响。方法:取大鼠分别用基础饲料和高脂饲料喂养8周后,分为正常对照组、肥胖组、肥胖-利拉鲁肽组,前2组大鼠腹腔注射0.9%氯化钠注射液,肥胖-利拉鲁肽组大鼠腹腔注射利拉鲁肽100μg/kg,每日2次,连续8周。末次给药后隔夜禁食处死大鼠,称体质量,取肾周及睾周脂肪组织,计算脂体比,检测脂肪组织中类蛋白质激酶激活的双链RNA的内质网激酶(PERK)、肌醇需求激酶1-α(IRE1-α)、C/EBP同源蛋白(CHOP)mRNA的表达和葡萄糖转运蛋白78(GRP78)的表达。结果:与正常对照组比较,肥胖组大鼠体质量、脂体比和脂肪组织中PERK、IRE1-α、CHOP mRNA及GRP78蛋白表达均明显升高(P<0.01);与肥胖组比较,肥胖-利拉鲁肽组大鼠上述指标均明显降低(P<0.01)。结论:利拉鲁肽可显著减轻肥胖大鼠体质量及内脏脂肪组织过度累积,并可缓解脂肪组织内质网应激。

OBJECTIVE：To study the effects of liraglutide on endoplasmic reticulum stress of fatty tissue in obese rats.METHODS：48 rats were divided into normal control group,obesity group and obesity-liraglutide group after given basal feed and high-fat diet for 8 weeks.The first 2 groups were given 0.9% Sodium chloride injection intraperitoneally,and obesity-liraglutide group was given intraperitoneal injection of liraglutide 100 μg/kg twice a day for consecutive 8 weeks.All rats were fasting overnight and sacrificed after last administration.Each rat of three groups was weighted,and the fatty tissue around kidney and epididymis were removed to calculate lipid ratio.The expressions of PERK,IRE1-α,CHOP mRNA and GRP78 protein in fatty tissue were measured.RESULTS：Compared with normal control group,the body weight,lipid ratio and the expressions of PERK,IRE1-α,CHOP mRNA and GRP78 protein in fatty tissue of obesity group were increased significantly（P〈0.01）;compared with obesity group,the above index of obesity-liraglutide group were decreased significantly（P〈0.01）.CONCLUSIONS：Liraglutide may ameliorate the body weight gain in obese rats and excessive accumulation of visceral adipose tissue,and significantly relieve endoplasmic reticulum stress in the fatty tissue.