氯氮平对雄性C57BL/6小鼠淀粉酶和促炎性细胞因子表达的影响  

Effects of clozapine on the expression of amylase and proinflammatory cytokines in male C57BL/6 mice

作　　者：赵彤彤 宁晓帅 杨亚婷 张雨龙 任振华[3] 刘寰忠[1,2] Zhao Tongtong;Ning Xiaoshuai;Yang Yating(Dept of Psychiatry,The Chaohu Affiliated Hospital of Anhui Medical University,Hefei 238000;Anhui Psychiatric Center of Anhui Medical University,Hefei 238000)

机构地区：[1]安徽医科大学附属巢湖医院精神科,合肥238000 [2]安徽医科大学安徽省精神医学中心,合肥238000 [3]安徽医科大学基础医学院解剖教研室,合肥230032

出　　处：《安徽医科大学学报》2021年第10期1527-1531,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81771449);安徽省转化医学研究院科研基金(编号:2017zhyx17)。

摘　　要：目的研究不同剂量氯氮平对雄性C57BL/6小鼠血清及其胰腺组织中淀粉酶(amylase)和促炎性细胞因子[白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α]表达的影响。方法将雄性C57BL/6小鼠随机分成对照组、氯氮平(5、10、20 mg/kg)组,分别给予0.9%氯化钠溶液、氯氮平(5、10、20 mg/kg)灌胃,连续灌胃14 d后采血测定各组小鼠amylase和促炎性细胞因子(IL-1β、IL-6和TNF-α)的水平;随后取小鼠胰腺组织,用Western blot方法检测胰腺组织amylase和促炎性细胞因子(IL-1β、IL-6和TNF-α)蛋白的表达,用荧光定量PCR方法检测胰腺组织amylase和促炎性细胞因子(IL-1β、IL-6和TNF-α)mRNA的表达。结果与对照组相比,氯氮平10、20 mg/kg组血清amylase水平明显升高(P<0.01,P<0.001);与对照组相比,氯氮平三组的血清IL-1β水平剂量依赖性地升高(P<0.01,P<0.001);与对照组相比,血清IL-6水平在氯氮平5 mg/kg组有所下降(P<0.05)。氯氮平剂量依赖性地升高小鼠胰腺组织amylase和促炎性细胞因子(IL-1β、IL-6和TNF-α)蛋白以及mRNA的表达水平,与对照组相比,差异均有统计学意义(P<0.01)。结论氯氮平可以升高血清amylase和促炎性细胞因子IL-1β的水平,并增加胰腺组织中amylase和促炎性细胞因子IL-1β、IL-6和TNF-α的表达,可能是氯氮平使用后易出现高淀粉酶血症乃至胰腺炎的发生机制之一。Objective To investigate the effects of different doses of clozapine on the expression of amylase and pro-inflammatory cytokines[interleukin 1β(IL-1β),interleukin 6(IL-6),and tumor necrosis factorα(TNF-α)]in the serum and pancreatic tissue of male C57BL/6 mice.Methods Male C57BL/6 mice were randomly divided into four groups.Mice were treated with clozapine 5,10 and 20 mg/kg or an equal volume of saline by gavage.Mice blood was collected to examine the levels of amylase and pro-inflammatory cytokines(IL-1β,IL-6 and TNF-α)after 14 days of consecutive gavage.Then the pancreases of the mice were dissected.Western blot was used to detect the expression of amylase,IL-1β,IL-6 and TNF-αprotein in pancreatic tissue.Fluorescence quantitative PCR method was used to detect the expression of amylase,IL-1β,IL-6 and TNF-αmRNA in pancreatic tissue.Results Compared with the control group,serum amylase levels significantly increased in the 10 and 20 mg/kg clozapine groups(P<0.01 and P<0.001).Compared with the control group,serum IL-1βlevel of the three clozapine groups increased in a dose-dependent manner(P<0.01,P<0.001).Compared with the control group,serum IL-6 level decreased in the clozapine 5 mg/kg group(P<0.05).Clozapine dose-dependently increased the expression of amylase,IL-1β,IL-6 and TNF-αprotein and mRNA in pancreatic tissues of mice,and the differences were statistically significant compared with the normal saline group(P<0.01).Conclusion Clozapine reliably increased the levels of serum amylase and IL-1β.Clozapine also increased the expression of amylase and pro-inflammatory cytokines IL-1β,IL-6 and TNF-αin pancreatic tissue,which may be one of the pathogenesis of clozapine-induced hyperamylasemia and even pancreatitis.

关 键 词：氯氮平 淀粉酶 促炎性细胞因子 白细胞介素-1Β 白细胞介素-6 肿瘤坏死因子-α 

分 类 号：R749.3[医药卫生—神经病学与精神病学]