二甲双胍对奥氮平及喹硫平所致大鼠糖脂代谢紊乱的防治作用

摘要

OBJECTIVE Tostudytheeffectofmetforminonglucolipidmetabolicdisorderscaused byolanzapineorquetiapineinrats.METHODS Olanzapine1mg·kg-1·d-1wasgivenigorquetiapine 20 mg·kg -1·d -1 was given ig for 4 d,and the dose increased to 40 mg·kg -1·d -1 from the 5th day.Met-formin 100 mg·kg -1·d -1 was given ig from the 15th day.The treatment lasted 8 weeks.Body mass, fasting blood sugar (FBS)and postprandial 2 hours blood glucose (2hPBG)were measured at base-line,3 d,1 week,2 week,4 week,6 week and 8 week.At the end of the 8th week,serum cholesterol (TC),triglyceride (TG),low density lipoprotein (LDL-C),high density lipoprotein (HDL-C),fruc-tosamine(FA)andinsulin(IRS)weremeasured.RESULTS Therewasnosignificantstatisticaldiffer-ence between normal control group and metformin 1 00 mg·kg -1·d -1 group.At the end of the 6th week, compared with normal control group,the body mass and 2hPBG were significantly increased in olanzap-ine 1 mg·kg -1·d -1 group and quetiapine 40 mg·kg -1·d -1 group (P<0.05),respectively.At the end of the 8th week,body mass,2hPBG,INS,FA,TC,TG,LDL-C were significantly increased (P<0.05), and HDL-C decreased in olanzapine group and quetiapine group(P<0.05),respectively.FBS was increased only in olanzapine group(P<0.05).Compared with olanzapine group or quetiapine group, body mass,FBS,2hPBG,INS,FA,TC,TG,LDL-C were significantly decreased by metformin admin-istration(P<0.05).CONCLUSION Metformincaneffectivelypreventandtreatweightgainand glucolipid metabolic disorder caused by olanzapine or quetiapine.%目的：探讨二甲双胍防治奥氮平和喹硫平所致大鼠糖脂代谢紊乱的作用。方法大鼠ig给予奥氮平1 mg·kg -1·d -1，从第15天开始，或第1～第4天大鼠i g给予喹硫平20 mg·kg -1·d -1，从第5天喹硫平加至40 mg·kg -1·d -1；第15天ig给予二甲双胍100 mg·kg -1·d -1；给药持续8周。分别于给药前和给药3 d、1周、2周、4周、6周及8周称大鼠体质量，同时测空腹血糖（FBS）及餐后2 h血糖（2 hPBG）；于实验第8周末采血，检测血清胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL-C）和高密度脂蛋白（HDL-C），并测血清果糖胺（FA）及胰岛素（I RS）水平。结果单独给予二甲双胍100 mg·kg -1各项指标与正常对照组无明显统计学差异。与正常对照组大鼠比较，第6周末单独给予奥氮平1 mg·kg -1或喹硫平组大鼠体质量和2hPBG均显著增加（P＜0．05）；在8周末，单独给奥氮平组和单独喹硫平组大鼠体质量、2hPBG、INS、FA、TC、TG和LDL-C上升（P＜0．05），HDL-C下降（P＜0．05），而FBS仅在单独给予奥氮平组显著上升（P＜0．05）；奥氮平组与喹硫平组相比，各指标无明显统计学差异（P＞0．05）。联用二甲双胍的两个组，与相应的单独给予奥氮平组或单独喹硫平组相比，第6和第8周末大鼠体质量、FBS、2hPBG、INS、FA 、TC、TG和LD L-C水平降低（P＜0．05），HD L-C下降（P＜0．05）。结论同时给予二甲双胍可对抗奥氮平或喹硫平所致的体质量增加及糖脂代谢紊乱。