大鼠胰岛β细胞经氯氮平和利培酮干预后胞内钙离子浓度的变化  

Changes of intracellular calcium concentration in beta cells of isolated rat islets after interventions of clozapine and risperidone

作　　者：刘浩[1] 王高华[1] 刘忠纯[1] 阳胜秋[1] 郭伶俐[1] 

机构地区：[1]武汉大学人民医院精神卫生中心,湖北省武汉市430060

出　　处：《中国临床康复》2006年第2期132-134,F0003,共4页Chinese Journal of Clinical Rehabilitation

摘　　要：目的:分析氯氮平和利培酮在低糖和高糖下对离体大鼠胰岛β细胞胞内钙离子浓度的影响,初步探讨其影响胰岛素分泌的可能机制。方法:实验于2005-01/2005-06在武汉大学医学院中心实验室完成。选择6～8周龄健康雌性SD大鼠10只,断头法处死实验鼠,无菌条件下开腹取出胰腺,在低糖和高糖条件下,以氯氮平、利培酮分别作用于分离培养的大鼠胰岛细胞,以Fluo-4/AM为荧光探针,并设空白对照组,应用激光扫描共聚焦显微镜实时动态监测不同药物作用后胰腺β细胞内钙荧光强度的变化规律。结果:实验动物10只,全部进入结果分析。①在低糖和高糖条件下,1μmol/L氯氮平、利培酮药物作用细胞后胞内钙荧光强度值的时间变化曲线,利培酮组曲线图形均与空白对照组基本一致;氯氮平组峰值低于利培酮作用组,稳定时胞内钙荧光强度值明显小于基线荧光强度值。②在低糖和高糖条件下,与空白对照组相比,氯氮平可降低胞内[Ca2+]i[(22±4),(93±6),P<0.01];[(62±10),(94±5),P<0.01],而利培酮对胞内[Ca2+]i无影响[(91±7),(93±6),P>0.05];[(91±8),(94±5),P>0.05]。结论:在低糖和高糖条件下,氯氮平可降低胞内[Ca2+]i,而利培酮对胞内[Ca2+]i无影响。推测氯氮平和利培酮对5-羟色胺1A受体亲合力不同可能是对胰岛分泌功能产生不同影响的原因之一。氯氮平和利培酮诱发血糖代谢紊乱可能与胰岛素分泌缺陷和胰岛素抵抗二者均有关。AIM： To analyze the different effects of clozapine and risperidone on the intracellular calcium concentration （[Ca^2＋]i in β cells of isolated rat islets under low and high glucose, and preliminarily discuss the possible mechanism in affecting the secretion of insulin. METHODS： The experiment was carried out in the central laboratory of Medical School of Wuhan University from January to June 2005. Ten healthy SD rats of 6-8 weeks were put to death by cutting off the head, and the pancreas was collected in aseptic condition. Under low and high glucose, the isolated and cultured rat islets were treated with clozapine and risperidone respectively, blank control group was also set, the changing law of [Ca^2＋]i represented by fluorescence intensity was measured by laser scanning confocal microscope after β cells were loaded with calcium sensitive fluorescent indicator Fluo-4/AM. RESULTS： All the 10 experimental animals were involved in the analysis of results. ①Under low and high glucose, the time changing curve of [Ca^2＋]i fluorescence graph after treatment of 1 μmol/L clozapine and risperidone in the risperidone group was similar to that in the clozapine group, the peak value in the clozapine group was lower than that in the risperidone group, and the stable [Ca^2＋]i fluorescence was obviously lower than the baseline level. ② Under low and high glucose, as compared with the blank control group, clozapine could decrease the [Ca^2＋]i[（22±4）, （93±6）, P 〈 0.01; （62±10）, （94±5）, P 〈 0.01], but risperidone had no influence on [Ca^2＋]i[（91±7）, （93±6）, P 〉 0.05; （91±8）, （94±5）, P 〉 0.05]. CONCLUSION： Under low and high glucose, cl0zapine can both decrease the [Ca^2＋]i, but risperidone has no influence on [Ca^2＋]i It is considered that the different affinity of clozapine and risperidone to 5-serotonin 1 receptor A may be one of the reasons for the different influence on the secretion of insulin. The disorder of glucose metabolism induced by cloz

关 键 词：氯氮平 利培酮 胰岛 钙离子 

分 类 号：R329.457[医药卫生—人体解剖和组织胚胎学]