利培酮通过提高IL-1β介导L型钙通道电流增加致大鼠结肠动力紊乱  

Risperidone induces colonic motility disorder through increasing L-type calcium channel current by IL-1β

作　　者：张家瑞 孙达亮[3] 毛富强[1] 李申[1] 赵钧铭 ZHANG Jia-rui;SUN Da-liang;MAO Fu-qiang;LI Shen;ZHAO Jun-ming(Department of Psychiatry,Tianjin Medical University,Tianjin 300070,China;Tianfin Union Medical Center,Tianjin 300121,China;Tianjin Anding Hospital,Tianjin 300222,China;Institute of Hematology ＆ Blood Diseases Hospital,Chinese Academy of Medical Science,Tianjin 300020,China)

机构地区：[1]天津医科大学精神卫生学系,天津300070 [2]天津市人民医院,天津300121 [3]天津市安定医院,天津300222 [4]中国医学科学院血液病医院血液学研究所,天津300020

出　　处：《中国新药杂志》2018年第18期2173-2179,共7页Chinese Journal of New Drugs

摘　　要：目的:探讨利培酮是否可通过增加结肠白细胞介素1β(IL-1β)介导结肠L型钙通道钙电流(LCC)改变,进而导致大鼠结肠动力紊乱。方法:正常大鼠灌胃(ig)给予0.15和0.6 mg·kg-1利培酮共14 d。d 15考察利培酮处理组大鼠排便习惯,大鼠离体结肠肌条收缩改变;考察血清以及结肠IL-1β表达变化;采用全细胞膜片钳考察利培酮以及IL-1β对结肠平滑肌细胞LCC作用。结果:利培酮处理组大鼠出现排便习惯改变,即排便数目以及粪便含水量显著下降;结肠平滑肌收缩张力显著增加;结肠IL-1β以及IL-1βmRNA相对于对照组显著增加;膜片钳实验中,IL-1β可显著增加LCC。结论:利培酮给药可显著增加大鼠结肠IL-1β表达,继而激发结肠LCC增加,致大鼠结肠紧张度增加,产生便秘等胃肠动力紊乱现象。本研究为降低利培酮临床应用的上述不良反应提供参考。Objective： To investigate whether risperidone induces colonic motility disorder through increasing L-type calcium channel calcium current（ LCC） by increasing the expression of interleukin-1β（ IL-1β）. Methods：Normal rats were administered with 0. 15 and 0. 6 mg·kg-1 risperidone by gavage for consecutively 14 days. On the15 th day,the changes of bowel evacuation habits and the contractile changes of isolated colonic muscle strips in the rats were respectively studied. The changes of IL-1β expression in serum and colon were studied. The effects of risperidone and IL-1β on the LCC of colonic smooth muscle cells were studied using whole cell patch clamp.Results： The defecation number and the fecal water content were significantly decreased in risperidone-treated rats.The contractile tension of colonic strips was significantly increased. The expressions of IL-1β and IL-1β mRNA in the colon were significantly increased compared with those in the control group; IL-1β significantly increased LCC.Conclusion： Risperidone can significantly increase the expression of IL-1β in colon,and then increase the LCCwhich leads to the increase of colonic contractile tension,resulting in gastrointestinal motility disorder. This study provided a reference for reducing the side effects of risperidone in clinical practice.

关 键 词：利培酮 便秘 结肠平滑肌收缩张力 IL-1Β L型钙通道 

分 类 号：R971[医药卫生—药品]