CAJ | 학술논문

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（2hPBG）；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，2hPBG、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、2hPBG 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、2hPBG、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。
목적：탐토이갑쌍고대방치록담평소치대서체질량증가、당지대사문란급간장지질침착적효과。방법안조불동약물장대서분위6조，진행약물간예。취0천、3천、1주、2주、4주、6주화8주분별칭취각조대서적체질량（Wt），검측공복혈당（FBS）급찬후2 h 혈당（2hPBG）；8주말검측혈지、혈청과당알（FA）급이도소（INS）수평，병취간장진행상규 HE 염색。결과여정상대조조비교，이갑쌍고조각시간점、각항지표차이균무통계학의의（P ＞0．05）。제6주、8주말，록담평조대서교정상대조조체질량증가명현，2hPBG、IRS、FA、TC、TG 급 LDL －C 승고，HDL －C 강저（P ＜0．05）；록담평＋신벌타정조、록담평＋대、소제량이갑쌍고조체질량、FBS、2hPBG 균교록담평조저，INS、FA、TC、TG 급 LDL －C 치경저，HDL －C 경고（P ＜0．05）；단록담평＋대、소제량이갑쌍고조여록담평＋신벌타정조비교，체질량、FBS、2hPBG、TC、TG、LDL －C 급 HDL －C차이무통계학의의（P ＞0．05）。간장병리시록담평조대서간세포형태유변화；기여4조대서간세포형태、혈관주위급원처백색지방침윤세포경접근정상대조조。결론록담평가인기대서체질량증가급당지대사문란，이갑쌍고능유효지방치록담평소치적대서체질량증가급당대사문란，병능감경간장지질침착。
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·kg -1 ·d -1 was gavaged,and the dose increased to 25 mg·kg -1 ·d -1 from the 5th day.Metformin 100 mg·kg -1 ·d -1 or 400 mg·kg -1 ·d -1 or simvastatin 1 mg· kg -1 ·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.