大麻素受体1对肥胖大鼠胰岛素抵抗的影响

Effects of cannabinoid receptor 1 on insulin resistance in obese rats

目的:探讨大麻素受体1(CB1受体)对肥胖大鼠胰岛素抵抗的影响。方法:32只雄性SD大鼠给予高脂鼠饲料喂养8周,制作肥胖大鼠模型。以给予普通鼠饲料喂养的6只大鼠作为正常组。将肥胖大鼠随机分为4组,S(模型组)、AW、W、A组,每组大鼠8只。正常组、模型组腹腔内注射等量生理盐水,W、A、AW组分别腹腔内注射CB1受体激动剂WIN55212-2、CB1受体抑制剂AM251、AM251+WIN55212-2;1次/d。2周后,测定大鼠血胰岛素、胰岛素原、C-肽水平,计算胰岛素原/C-肽、胰岛素原/胰岛素;进行高葡萄糖钳夹实验,计算相关参数,包括第1、2时相胰岛素分泌量(1PH和2PH)、胰岛素最大分泌量(MIS)及稳态葡萄糖输注率(GIR60-90)。结果:注药2周后,与正常组比较,模型组血胰岛素、胰岛素原、C-肽、胰岛素原/C-肽、胰岛素原/胰岛素及2PH、MIS水平升高,1PH及GIR60-90水平下降(P<0.05)。W组上述指标变化方向与模型组相同,但变化幅度大于模型组(P<0.05);A组上述指标变化方向与模型组相反,各指标水平与正常组比较,差异无统计学意义(P>0.05);AW组上述指标水平与模型组比较,差异无统计学意义(P>0.05)。结论:CB1受体激动可加重肥胖大鼠胰岛素抵抗,抑制CB1受体可逆转此效应。

Aim ： To study the effects of eannabinoid receptor 1 （ CBI ） on insulin resistance in obese rats. Methods ：32 male SD rats were given high-fat diet for 8 weeks to establish obese rat model, and then were randomly divided into model group, W group, A group and AW group, 8 in each group. 6 rats were given regular diet for 8 weeks as the normal control. Rats in W,A and AW groups were given CBI agonist（WlN55212-2）, CBI antagonist（AM251）, WIN55212-2 ＋AM251, respectively, and the normal control group and model group were given normal saline. Two weeks later, the serum fasting insulin, proinsulin and C-peptide （C-P） levels were measured, and proinsulin/C-P, proinsulin/insulin were calculated. Then hyperglycemic clamp was performed to evaluate the insulin sensitivity, the insulin secretion in Phase 1 （ 1 PH） , that in Phase 2（2PH）, the maximum insulin secretion（MIS）, and steady state glucose infusion rate（GIR60-90） were calculated. Results： Compared with those of the normal control group, the serum fasting insulin, proinsulin, C-P, proinsulin/C-P,proinsulin/insulin,2PH and M IS of model group were higher, and 1 PH and GIR60_90 were lower （P 〈 O. 05 ）. Compared with those of the model group, the serum fasting insulin, proinsulin, C-P, proinsulin/C-P,proinsulin/insulin,2PH and MIS of W group were higher（ P 〈 O. 05 ） , 1 PH and GIR60_90of W group were lower（ P 〈 O. 05 ） , The levels of the indicators mentioned above in A group were similar to those of the normal control group（ P 〉 0. 05 ）. The levels of the indicators mentioned above in AW group were similar to those of the model group（ P 〉 O. 05 ）. Conclusion： Agitating CBI receptor could aggravate obese rats＇ insulin resistance. Restraining CBI receptor could reverse these effectiveness.