二甲双胍对舒必利、利培酮所致大鼠糖脂代谢紊乱的影响

Effects of Metformin on Sugar Lipid Metabolic Disorder Caused by Sulpiride or Risperidone in Rats

关键词:  二甲双胍  舒必利  利培酮  糖脂代谢紊乱  脂质沉着

Key words:  metformin  sulpiride  risperidone  sugar lipid metabolic disorder  liver lipidosis

摘要:

目的 探讨二甲双胍防治抗精神病药舒必利、利培酮所致的大鼠体质量增加、糖脂代谢紊乱及肝脏脂质沉着的效果。方法 大鼠第1~4天予舒必利25 mg·kg^-1·d^-1或利培酮0.05 mg·kg^-1·d^-1灌胃，从第5日起舒必利加至50 mg·kg^-1·d^-1或利培酮加至0.1 mg·kg^-1·d^-1，2周后加用二甲双胍100 mg·kg^-1·d^-1，总共给药周期为8周；取基线，3 d，1周，2周，4周，6周，8周7个时间点，称取大鼠体质量，测空腹血糖(fasting blood-glucose，FBS)及餐后2 h血糖(2-hour post-meal blood glucose，2hPBG)；于实验第8周末检测血清果糖胺(fructosamine，FA)、胰岛素(insulin，IRS)水平血清胆固醇(total cholesterol，TC)、甘油三酯(triglyceride，TG)、低密度脂蛋白(low density lipoprotein cholesterol，LDL-C)及高密度脂蛋白(high density lipoprotein cholesterol，HDL-C)，并取大鼠肝脏进行常规HE染色。结果 各时间点二甲双胍组与正常对照组各相关指标差异无统计学意义；与正常对照组比较，服用舒必利组、利培酮组大鼠在第6周、8周末体质量、2hPBG、INS、FA升高(P<0.05)，8周末TC、TG、HDL-C升高(P<0.05)，LDL-C降低(P<0.05)，而舒必利与利培酮组比较，上述指标差异无统计学意义；舒必利或利培酮合用二甲双胍的大鼠6周及8周末体质量、2hPBG、INS、FA较单独使用舒必利或利培酮的大鼠更低(P<0.05)，8周末TC、TG、HDL-C更低(P<0.05)，LDL-C较高(P<0.05)。肝脏病理示舒必利及利培酮组大鼠肝细胞形态紊乱，血管周围见多量白色脂肪浸润细胞，且在距离血管较远的肝细胞也可见到脂质沉着；舒必利或利培酮合用二甲双胍的大鼠肝细胞形态整齐，血管周围及血管较远白色脂肪浸润细胞明显少于舒必利及利培酮组。结论 抗精神病药舒必利、利培酮可引起大鼠体质量增加、血糖升高、糖耐量异常、脂代谢紊乱及肝脏脂质沉着，二甲双胍能有效地防治舒必利、利培酮所致的大鼠体质量增加及糖脂代谢紊乱，并能减轻肝脏脂质沉着。

Abstract:

OBJECTIVE To study using metformin to prevent and treat body weight increasing, sugar lipid metabolic disorder and liver lipid deposition which are caused by sulpiride or risperidone in rats. METHODS From 1 d to 4 d, sulpiride 25 mg·kg^-1·d^-1 or isperidone 0.05 mg·kg^-1·d^-1 was gavaged; and from the 5th day, sulpiride 50 mg·kg^-1·d^-1 or isperidone 0.1 mg·kg^-1·d^-1 was gavaged; from 15th day, metformin 100 mg·kg^-1·d^-1 was added. The total period of dosing was 8 weeks. weight, fasting blood sugar(FBS) and postprandial 2 hours blood glucose(2hPBG) were measured at inbaseline, 3 d, 1st, 2nd, 4th, 6th and 8th week. At the end of 8th week, serum cholesterol(TC), triglyceride(TG), low density lipoprotein (LDL-C), high density lipoprotein(HDL-C), fructosamine(FA) and insulin(IRS) were measured, and HE staining in rat livers. RESULTS Compared with normal control group, all the indicators in metformin group had no significant statistical difference. At 6th and 8th week, rats weight, 2hPBG, INS and FA in sulpiride group or risperidone group were higher than normal control group(P<0.05), rat weight, 2 HPBG, INS and FA in sulpiride+metformin group or rispidone+metformin group were lower than sulpiride group or rispidone group(P<0.05). At the end of 8th week, TC, TG and HDL-C in sulpiride group or risperidone group were higher than normal control group(P<0.05), LDL-C was lower(P<0.05); TC, TG and HDL-C in sulpiride+metformin group or risperidone+metformin group were lower than sulpiride and risperidone group(P<0.05), LDL-C were higher(P<0.05). Liver HE staining pathologic examination showed that compared with normal control group, rat liver cells in sulpiride group and risperidone group arrangement were not neat, around the small blood vessels, there were more white fat cells and hepatocellular lipid calm far away from the blood vessels; sulpiride+metformin group and risperidone+metformin group had normal liver cells, there were moderate white fat cells, and there were not much hepatocellular lipid calm far away from the blood vessels. CONCLUSION Antipsychotics sulpiride and risperidone result in weight gain and glucolipid metabolic disorder in rats, just as clinical observation report, metformin effectively prevent and treat weight gain and glucolipid metabolic disorder, which are caused by sulpiride and risperidone.