大麻素受体1激动剂和抑制剂对肥胖大鼠胰岛β细胞功能的影响

Effects of cannabinoid-1 receptor on pancreatic beta-cell function in obese rats

目的 研究大麻素受体1对肥胖大鼠胰岛β细胞功能的影响.方法 30只8周龄清洁级健康雄性SD大鼠,体质最150～200 g,采用数字表法随机分至正常对照组(n=6)和肥胖组(n=24).正常对照组给予普通鼠饲料喂养,肥胖组给予高脂鼠饲料喂养.8周后,与正常对照组比较,肥胖纽大鼠体质量增加36%,总胆固醇增加52%,提示24只肥胖大鼠制作成功.肥胖大鼠以数字表法随机分至生理盐水组(n=8)、WIN55212-2组(n=8)、AM251组(n=8).测定大鼠体质量、血脂、胰岛素、胰岛素原等指标,采用高葡萄糖钳央试验评价胰岛β细胞功能和胰岛素敏感性.采用LSD检验进行统计学分析.结果 腹腔注射药物2周后,生理盐水组、WIN55212-2组体质量、血脂、卒腹血糖、C肽、胰岛素、胰岛素原、胰岛素原/C肽、胰岛素原/胰岛素、胰岛素10～90 min分泌量及胰岛素最大分泌量均高于正常对照组(P<0.05),WIN55212-2组上述指标均高于生理盐水组(P<0.05),AM251组上述指标均低于生理盐水组和WIN55212-2组(P<0.05).生理盐水组、WIN55212-2组胰岛素0～10 min分泌量、匍萄糖输注率低于正常对照组(P<0.05),WIN55212-2组胰岛素0～10 min分泌量、葡萄糖输注率低于生理盐水组(P<0.05).AM251组胰岛素0～10 min分泌量、葡萄糖输注率高于生理盐水组和WIN55212-2组(P<0.05).结论 大麻素受体1受体激动可增加肥胖大鼠体质量,升高血脂水平,加重胰岛素抵抗和胰岛β细胞功能减退,抑制大麻素受体1可逆转此效应.

Objective To investigate the effects of cannabinoind-1 receptor (CB1R) on pancreatic beta-cell function in obese rats. Methods A total of 30 male 8-week healthy SD rats were randomly assigned to the control group (n=6) or obesity group (n=24). After 8 weeks' intervention, 24 obese rats were randomly divided into the saline group (n=8), WIN55212-2 injection group (n=8) and AM251 injection group (n=8). The body weight, insulin, lipids, and proinsulin levels were measured in fasting status. Hyperglycemic clamp was performed to evaluate the insulin sensitivity and islet beta-cell function. LSD test was used for data analysis. Results After 2-week peritoneal injection, compared with the control group, body weight, lipids, fasting glucose, C peptide, insulin, proinsulin, proinsulin/C peptide, proinsulin/insulin, 10 to 90 min insulin release and maximum insulin secretion were significantly higher in the saline or WIN55212-2 injection group (all P <0.05). These parameters in the WIN55212-2 injection group were higher than those in the saline group (all P < 0.05). Above measurements in the AM251 injection group were lower than those in the saline or WIN55212-2 injection group (all P < 0.05). Compared with the control group, 0 to 10 min insulin release and glucose infusion rate (GIR) were significantly lower in the saline or WIN55212-2 injection group (all P < 0.05). GIR and 0 to 10 min insulin release in the WIN55212-2 injection group were lower than those in the saline group. GIR and 0 to 10 min insulin release in the AM251 injection group were higher than those in the saline or WIN55212-2 injection group. Conclusion Agitating CB1R could elevate body weight, lipid profile, insulin resistance and islet beta-cell function impairment in obese rats. Restraining CB1R could reverse those effectiveness.