【作者】 董介正； 沈鉴清； 邱龄山； 刘义； 宋旦哥； 徐莲莲；

【Author】 Dong Jiezheng;Shen Jian-qing;Qiu Ling-shan;Liu Yi;Song Dan-ge;Xu Lian-lian;The Seventh PeoPle’s HosPital of Hangzhou;

【机构】 杭州市第七人民医院；

【摘要】 目的:探讨决明子水提物对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:选用取2月龄SD大鼠50只,清洁级,雌雄各半,体质量170~200g,按其体质量用随机数字表法分为5组,每组10只,即正常对照组,氯氮平组,氯氮平辛伐他汀组,氯氮平小剂量决明子组及氯氮平大剂量决明子组。氯氮平的使用方法为1~4天5mg·kg-1·d-1,第5日起加至25 mg·kg-1·d-1,总共使用时间为8周。2周后在使用氯氮平的同时分别予辛伐他汀1 mg·kg-1·d-1、决明子水提液1000mg·kg-1·d-1及4000mg·kg-1·d-1干预,氯氮平组不予其它药物,正常对照组仅予生理盐水;取基线、3d、1w、2w、4w、6w、8w等7个时间点,称取大鼠体质量(Wt.),测空腹血糖(FBS)及餐后两小时血糖(2hPBG);于实验第8w末采血,检测血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C),并测血清果糖胺(FA)及胰岛素(IRS)水平,并取大鼠肝脏进行常规HE染色。结果:第6w、8w末,氯氮平组大鼠体质量与正常对照组大鼠体质量比较增加明显,FBS及2hPBG升高,血IRS、FA、TC、TG、LDL-C升高、HDL-C降低,表明氯氮平可引起大鼠体重增加,空腹血糖升高、糖耐量异常及脂代谢紊乱;第6w、8w末,与氯氮平组相比,氯氮平+辛伐他汀组、氯氮平+决明子大、小剂量组体质量较轻,FBS及2hPBG升高幅度小、IRS、FA、TC、TG、LDLC水平低、HDL-C略高;与阳性对照氯氮平+辛伐他汀组比较,氯氮平决明子大、小剂量组在减轻体质量增加,降血脂方面均无明显差异,决明子大剂量组在降低血糖方面优于氯氮平辛伐他汀组,表明决明子可以防治氯氮平所致体重增加,且较大剂量效果更明显。肝脏病理示与正常对照组比,氯氮平组镜下可见大鼠肝细胞形态紊乱,血管周围见多量白色脂肪细胞胞,且在距离血管较远的肝细胞也可见到脂质沉着,氯氮平+小剂量决明子组大鼠肝细胞形态正常,血管周围见较多量白色脂肪细胞胞,氯氮平+辛伐他汀组及氯氮平+大剂量决明子组大鼠肝脏小血管周围见少量白色脂肪细胞胞,血管较远处肝细胞无明显脂质沉着。结论:非典型抗精神病药物氯氮平可造成大鼠体质量增加、糖脂代谢紊乱及肝脏脂质沉着,决明子水提物能有效地防治非典型抗精神病药氯氮平所致的大鼠体质量增加、糖脂代谢紊乱及肝脏脂质沉着。更多还原

【Abstract】 Objective To study using Semen Cassiae to Prevent and treat body weight increasing and Sugar Metabolic Disorder in rats,which are caused by ClozaPine.Methods Choose 50 2-month-old clean Level SD rats,170~200 g,randomly divided into 5 groups,there were 10 rats in each group,namely Normal control group,Clozapine group,Clozapine +simvastatin group,Clozapine +low-dose Semen Cassiae group,Clozapine+High-dose Semen Cassiae group.Drug intervene as follows:5 mg·kg-1·d-1 Clozapine was gavaged for 4 days,and then add to 25 mg·kg-1·d-1,the total period was 8 weeks.From 2-8weeks,simvastatin 1 mg·kg-1·d-1,semen cassiae 1000mg·kg-1·d-1 cassia 4000mg·kg-1·d-1.were respectively gavaged to each rats;normal control group:3-5ml saline water a day;Clozapine group gavaged clozapine only.Take baseline,3d,1 w,2 w,4 w,6 w and 8 w as time points to take sampies,respectively,take each group rats’ body weight(Wt.),fasting blood sugar(FBS),2 hours postprandial blood glucose(2HPBG);In the end of 8 w,take the femoral artery blood,to test serum cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C),high density lipoprotein(HDL-C),and measured serum fructosamine(FA) and insulin(IRS) level and liver HE staining.Results At the end of 8 w,compared with normal control group rats,Clozapine Group body weight,FBS,2 HPBG,INS and FA TC、TG、LDL-C are higher(P<0.05),HDLC are lower(P<0.05),indicate that atypical antipsychotic clozapine can result in rat body weight gain and sugar lipid metabolic disorder;At the end of 8 w,Clozapine + simvastatin group,Clozapine +low-dose Semen Cassiae group,ClozaPine+ High-dose Semen Cassiae group rats compared with Clozapine group,Wt,2HPBG,INS and FA were lower(P<0.05),Clozapine+High-dose Semen Cassiae group rats FBS were lower(P<0.05).Liver HE colorration pathologic examination shows that compared with Normal Control Group,rat liver cells in Clozapine Group are not neat,around the small blood vessels we can see more white fat cells,and there were hepatocellular lipid calm cells far away from the blood vessels.Clozapine +simvastatin group,Clozapine +low-dose Semen Cassiae group,Clozapine+High-dose Semen Cassiae group have normal liver cells,there are moderate white fat cells,and there are not much hepatocellular lipid calm far away from the blood vessels.It showed that clozapine can result in abnormal lipid metabolism,semen cassiae can effectively prevent and treat lipid metabolism disorders caused by clozapine.Conclusion Atypical antipsychotic clozapine can cause rat body weight gain and sugar lipid metabolic disorder and Liver Lipid Deposition,semen cassiae can effectively Prevent and treat body weight increasing and Sugar lipid Metabolic Disorder and Liver Lipid Deposition in rats,which are caused by Clozapine.更多还原