摘要
目的 观察胰高血糖素样肽1(GLP-1)受体激动剂利拉鲁肽皮下注射对肥胖雄性小鼠血清性激素水平的影响.方法 取雄性C57BL/6J小鼠18只,随机分为正常组、模型组、干预组,每组各6只.正常组给予普通饲料喂养,模型组和干预组通过给予高脂饲料喂养建立肥胖模型;饲养10周后造模成功,干预组皮下注射利拉鲁肽100 μg/(kg·d),正常组和模型组给予等体积生理盐水皮下注射,连续12周.每周测量小鼠体质量;给药结束后使用血糖试纸测量空腹血糖(FBG),ELISA法检测血清胰岛素(INS)、黄体生成素(LH)、促卵泡激素(FSH)、睾酮(T)、游离睾酮(FT)、雌二醇(E2)和性激素结合球蛋白(SHBG),计算胰岛素抵抗指数(HOMA-IR).结果 与正常组比较,模型组0、4、8、12周时体质量均升高(P均<0.01);与模型组比较,干预组4、8、12周时体质量均降低(P均<0.01);12周时,干预组体质量与正常组比较差异无统计学意义(P>0.05).给药结束后,与正常组比较,模型组血清FBG、INS、HOMA-IR升高(P均<0.01);与模型组比较,干预组血清FBG、INS、HOMA-IR降低(P均<0.01).与正常组比较,模型组血清LH、FSH、T、FT水平降低,E2、SHBG水平升高(P均<0.05);与模型组比较,干预组血清LH、FSH、T和FT水平升高,E2和SHBG水平降低(P均<0.05).结论 肥胖雄性小鼠的性激素水平存在异常;利拉鲁肽能够改善肥胖雄性小鼠的性激素水平,其机制可能与其显著降糖及减轻体质量的作用有关.
Abstract
Objective To investigate the effects of subcutaneous injection of glucagon-like peptide-1(GLP-1)re-ceptor agonist liraglutide on serum sex hormone levels in obese male mice.Methods Eighteen male C57BL/6J mice were randomly divided into the normal group(n=6),model group(n=6),and intervention group(n=6).Mice in the nor-mal group were fed with normal diet,and mice in the model group and intervention group were fed with high-fat diet to es-tablish the obesity models.After 10 weeks,mice in the intervention group were subcutaneously injected with liraglutide at 100 μg/(kg·d),and mice in the normal group and model group were subcutaneously injected with the equal volume of nor-mal saline for 12 weeks.Body weight was measured weekly.Fasting blood glucose(FBG)was measured using a blood glu-cose test strip.The serum levels of insulin(INS),luteinizing hormone(LH),follicle-stimulating hormone(FSH),testos-terone(T),free testosterone(FT),estradiol(E2),and sex hormone binding globulin(SHBG)were detected using ELI-SA.The homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.Results Compared with the normal group,the body weight of the model group increased at 0,4,8,and 12 weeks(all P<0.01);compared with the model group,the body weight of the intervention group decreased at 4,8,and 12 weeks(all P<0.01);there was no statis-tically significant difference in body weight between the intervention group and the normal group at 12 weeks(P>0.05).After administration,compared with the normal group,the serum FBG,INS,and HOMA-IR levels increased in the model group(all P<0.01);compared with the model group,the serum FBG,INS,and HOMA-IR levels decreased in the inter-vention group(all P<0.01).Compared with the normal group,the levels of LH,FSH,T,and FT decreased and the lev-els of E2 and SHBG increased in the model group(all P<0.05);compared with the model group,the levels of LH,FSH,T,and FT in the intervention group increased,and the levels of E2 and SHBG decreased(all P<0.05).Conclusion The sex hormone levels of obese male mice are abnormal;liraglutide can improve the sex hormone levels of obese male mice,and its mechanism may be related to its significant effects of reducing blood glucose and body mass.
基金项目
广西自然科学基金面上项目(2020GXNSFAA297128)