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背景:氯氮平所致的糖代谢障碍越来越引起内分泌科医生的关注,胰岛素抵抗被认为与其发生有关,那么氯氮平是否也直接影响胰岛分泌功能。目的:观察不同浓度氯氮平在不同条件下对体外培养大鼠胰岛分泌功能的影响。设计:完全随机分组设计,对照实验,采用一元方差分析比较实验组和对照组之间的差异,采用LSD-t检验作多个样本间的两两比较(多重比较)。单位:武汉大学人民医院精神卫生中心。材料:实验于2003-09/2004-01在武汉大学口腔医院实验中心完成。选用清洁级健康雄性Wistar大鼠3只。方法:①采用经典的胶原酶消化法分离、纯化胰岛。②以含2g/L牛血清白蛋白和3.3mmol/L葡萄糖的Hanks液每孔1mL,预孵育30min,弃上清。每12孔为一组,共5组:对照组的孵育液含1g/L二甲基亚砜、3.3mmol/L或16.7mmol/L的葡萄糖液1mL;4个不同浓度氯氮平组的孵育液除含有上述成分外,还分别含浓度为0.2,1.0,5.0或10.0μmol/L氯氮平;各组有6孔继续孵育1h,另外6孔继续孵育4h;吸取上清液,保存于-20℃冰箱中待测。重复3次。采用放射免疫分析法测定上清液中胰岛素分泌量。③采用一元方差分析(ANOVA)比较实验组和对照组之间的差异,采用LSD-t检验作多个样本间的两两比较(多重比较)。主要观察指标:培养液葡萄糖浓度为3.3,16.7mmol/L,作用1,4h各组胰岛素分泌量比较。结果:①培养液葡萄糖浓度为3.3mmol/L,培养1h,氯氮平各浓度组胰岛素分泌量与对照组相近(P>0.05);培养4h,4种浓度氯氮平组胰岛素分泌量明显低于对照组犤(0.92±0.4),(1.02±0.3),(1.06±0.4),(0.74±0.2),(1.66±0.4)mU/IEQ,P<0.05犦,但各浓度组间差异不明显(P>0.05)。②培养液葡萄糖浓度为16.7mmol/L,培养1和4h,4种浓度氯氮平组胰岛素分泌量均与对照组相近(P>0.05)。结论:氯氮平抑制基础胰岛素分泌,与剂量无关。
BACKGROUND: Clozapine-induced glucose metabolism disorders are increasingly causing the concern of endocrinologists. Insulin resistance is thought to be related to its occurrence, and whether or not clozapine also directly affects pancreatic islet secretion. OBJECTIVE: To observe the effects of clozapine at different concentrations on rat pancreatic islet secretory function under different conditions. DESIGN: Complete randomized block design, controlled trials, one-way ANOVA to compare differences between experimental and control groups, and LSD-t tests for pairwise comparisons among multiple samples (multiple comparisons). Unit: People’s Hospital of Wuhan University mental health center. MATERIALS: The experiment was performed at the Experimental Center of Stomatology, Wuhan University from September 2003 to January 2004. Three healthy male Wistar rats were selected. Methods: ①Using classic collagenase digestion method to isolate and purify pancreatic islets. ② Hanks solution containing 2g / L bovine serum albumin and 3.3mmol / L glucose 1mL per well, pre-incubated for 30min, the supernatant was discarded. Each group of 12 wells for a group of 5 groups: the control group of incubation solution containing 1g / L dimethyl sulfoxide, 3.3mmol / L or 16.7mmol / L glucose solution 1mL; 4 different concentrations of clozapine group incubation In addition to the above-mentioned components, the liquid also contained clozapine at a concentration of 0.2, 1.0, 5.0 or 10.0 μmol / L, respectively; each group of 6 wells was incubated for 1 hour and the other 6 wells were incubated for 4 hours; the supernatant was aspirated, 20 ℃ refrigerator to be measured. Repeat 3 times. The amount of insulin secretion in the supernatant was determined by radioimmunoassay. ③ One-way ANOVA (ANOVA) was used to compare the differences between the experimental group and the control group, using LSD-t test for comparison of multiple samples (multiple comparison). MAIN OUTCOME MEASURES: The concentration of glucose in culture medium was 3.3, 16.7mmol / L, the role of insulin secretion in each group 1,4h comparison. Results: ① The concentration of glucose in culture medium was 3.3mmol / L, and the secretion of insulin in each concentration of clozapine was similar to that of control group (P> 0.05) after incubation for 1h. After cultured for 4h, the insulin secretion of clozapine group was significantly lower (0.92 ± 0.4), (1.02 ± 0.3), (1.06 ± 0.4), (0.74 ± 0.2), (1.66 ± 0.4) mU / IEQ, P <0.05 犦 in the control group, but there was no significant difference between the groups (P> 0.05). ② The concentration of glucose in culture medium was 16.7mmol / L, cultured for 1 and 4h. The insulin secretion of clozapine group was similar to that of control group (P> 0.05). CONCLUSION: Clozapine inhibited basal insulin secretion independent of dose.