摘要
目的探讨二甲双胍对防治氯氮平所致大鼠体质量增加、糖脂代谢紊乱及肝脏脂质沉着的效果。方法按照不同药物将大鼠分为6组,进行药物干预。取0天、3天、1周、2周、4周、6周和8周分别称取各组大鼠的体质量(Wt),检测空腹血糖(FBS)及餐后2 h血糖(2h PBG);8周末检测血脂、血清果糖胺(FA)及胰岛素(INS)水平,并取肝脏进行常规HE染色。结果与正常对照组比较,二甲双胍组各时间点、各项指标差异均无统计学意义(P>0.05)。第6周、8周末,氯氮平组大鼠较正常对照组体质量增加明显,2h PBG、IRS、FA、TC、TG及LDL-C升高,HDL-C降低(P<0.05);氯氮平+辛伐他汀组、氯氮平+大、小剂量二甲双胍组体质量、FBS、2h PBG均较氯氮平组低,INS、FA、TC、TG及LDL-C值更低,HDL-C更高(P<0.05);但氯氮平+大、小剂量二甲双胍组与氯氮平+辛伐他汀组比较,体质量、FBS、2h PBG、TC、TG、LDL-C及HDL-C差异无统计学意义(P>0.05)。肝脏病理示氯氮平组大鼠肝细胞形态有变化;其余4组大鼠肝细胞形态、血管周围及远处白色脂肪浸润细胞更接近正常对照组。结论氯氮平可引起大鼠体质量增加及糖脂代谢紊乱,二甲双胍能有效地防治氯氮平所致的大鼠体质量增加及糖代谢紊乱,并能减轻肝脏脂质沉着。
Objective To study the effect of metformin on glucolipid metabolic disorders and liver lipid deposition caused by clozapine in rats.Methods From 1 d to 4 d,Clozapine 5 mg＆#183;kg -1 ＆#183;d -1 was gavaged,and the dose increased to 25 mg＆#183;kg -1 ＆#183;d -1 from the 5th day.Metformin 100 mg＆#183;kg -1 ＆#183;d -1 or 400 mg＆#183;kg -1 ＆#183;d -1 or simvastatin 1 mg＆#183; kg -1 ＆#183;d -1 was gavaged from the 15th day.The total period of dosing was 8 weeks.Body mass,fasting blood sugar （FBS） and postprandial 2 hours blood glucose （2hPBG）were measured at baseline,3 d,1 week,2 weeks,4 weeks,6 weeks and 8 weeks.At the end of the 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 liver HE staining was done.Results There were no significant differences of the measured indexes between control group and metformin group at the all test points.By the end of the 6th and 8th week,compared with control group,the body mass,FBS,2hPBG,IRS, FA,TC,TG and LDL -C were significantly increased in clozapine group （P〈0.05 ）,while HDL -C decreased in clozapine group （P〈0.05）.Compared with clozapine group,body mass,FBS,2hPBG,IRS,FA,TC,TG and LDL -C were significantly decreased by metformin or simvastatin administration （P〈0.05）,while HDL -C increased（P〈0.05）.Rat liver cells in clozapine group were not neat around the small blood vessels;there were more white fat cells and hepatocellular lipid calm far away from the blood vessels.However,in other groups,there were moderate white fat cells, and there were not much hepatocellular lipid calm far away from the blood vessels.Conclusion Metformin could effectively prevent and treat weight gain,glucolipid metabolic disorder and liver lipid deposition caused by clozapine.
出处
《浙江预防医学》
2015年第5期440-444,共5页
Zhejiang Journal of Preventive Medicine
基金
杭州市科技局重点医药卫生项目(20110833B21)
杭州市卫生局一般项目(2012A039)
浙江省中医药管理局项目(2011ZB112)
关键词
二甲双胍
氯氮平
糖脂代谢紊乱
肝脏脂质沉着
Metformin
Clozapine
Glucolipid metabolic disorder
Liver lipid deposition
作者简介
通讯作者：董介正，硕士，医师，主要从事精神医学I临床药理学方面研究工作E-mail：djzh105@126．com
