5-羟色胺与氯氮平致糖脂代谢紊乱的相关性探讨

目的 通过研究非典型性抗精神病药氯氮平单用及与5-羟色胺合用对小鼠糖脂代谢的影响,探讨氯氮平致糖脂紊乱与5-羟色胺之间的关系.方法 42只雄性小鼠随机分为6组,分别为空白组、氯氮平4 mg/kg组、氯氮平20 mg/kg组、5-HT 20 mg/kg组、氯氮平4 mg/kg+5-HT 20mg/kg组和氯氮平20 mg/kg+5-HT 20 mg/kg组,分别于给药1周和4周时测定小鼠的空腹血糖和糖耐量,4周后测定小鼠血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、血清胰岛素(Ins)和空腹血糖(FBG).结果 (1)单用氯氮平20 mg/kg可使小鼠糖耐量、TG、LDL-C、TC和HO-MA-IR水平升高,降低HDL-C水平.(2)5-羟色胺与氯氮平联用可改善糖耐量,显著降低单用氯氮平导致的TG、LDL-C、TC和HOMA-1R水平,同时升高HDL-C水平.结论 氯氮平导致的小鼠糖脂代谢紊乱可能与其抑制5-羟色胺受体有关.

Study of the relationship between serotonin and clozapine-induced glucose and lipid metabolism disorders

Objective To study the effects of co-administration of clozapine and serotonin versus clozapine monotherapy on the glucose and lipid metabolism in the male mice and investigate the relationship between serotonin and clozapine-induced glucose and lipid metabolism disorders.Methods Totally 42 male mice were divided into 6 groups: vehicle group,clozapine 4 mg/kg treatment group,clozapine 20 mg/kg treatment group,5-HT 20 mg/kg treatment group,clozapine 4 mg/kg+5-HT 20 mg/kg treatment group,clozapine 20 mg/kg+5-HT 20 mg/kg treatment group.Oral glucose tolerance test was conducted after ig/ip medication for one and four weeks,and the contents of triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),insulin(Ins),fasting plasma glucose(FBG)in serum were detected at the end of the experiment.Results The glucose tolerance,TG,LDL-C,TC and HOMA-IR of the male mice were increased,HDL-C was decreased in the clozapine 20 mg/kg treatment group.Compared with clozapine monotherapy group,the co-administration of 5-HT(20 mg/kg) could attenuate the clozapine-induced impaired glucose tolerance,the level of TG,LDL-C,TC and HOMA-IR were decreased and HDL-C enhanced.Conclusion Mice caused by clozapine glucose and lipid metabolism disorders may be related to the inhibition of serotonin.