氯丙嗪致大鼠便秘与炎性细胞因子表达的对照研究

Expression of cytokines is partially involved in the constipation induced by chlorpromazine

目的探讨氯丙嗪应用对大鼠肠道炎症反应以及排便习惯的作用及相关机制。方法 50只SD雄性大鼠随机分为正常对照组,氯丙嗪低中高剂量组,以及氯丙嗪联合新斯的明给药共五组,灌胃氯丙嗪两周以后,考察氯丙嗪对大鼠排便习惯以及肠推动力的影响;分离提取结肠组织,采用酶联免疫反应以及Western blotting考察氯丙嗪对前炎性因子,炎性介质以及诱导型一氧化氮(NO)合酶(i NOS)、环氧合酶-2(COX-2)以及核转录因子(NF-κB)表达的作用。结果灌胃氯丙嗪(40 mg/kg)两周以后,与正常对照组相比,大鼠排便数量以及粪便含水量分别从(81±15)%,(60±13)%下降至(33±21)%,(25±27)%(P均<0.05),分离的大鼠结肠i NOS,COX-2以及NF-κB分别从(100±11)%,(100±9)%,(100±12)%增加至(289±19)%、(311±28)%、(209±18)%(P均<0.05),同时伴随着结肠中相关细胞因子以及炎性介质的增加。结论氯丙嗪长期使用,可使NF-κB活化,继而激活i NOS和COX-2,前炎性因子以及炎性介质进一步高表达,导致结肠炎症。

Objective To investigate the effects of chlorpromazine on bowel movements as well as intestinal inflammation in rats and uncover the related mechanisms. Methods Fifty male SD rats were randomly divided into 5 groups including normal control, low middle and high dose of chlorpromazine, as well as neostigmine treated chlorpromazine group. After two weeks of the application of chlorpromazine, the effects of Chlorpromazine on rat bowel movements and intestinal propulsion were studied ; the expressions of induc- ible nitric oxide （iNOS） synthase, cyclooxygenase -2 （COX -2）, NF - KB were respectively studied using ELISA and Western blot- ting methods. Results After two weeks of cblorpromazine application （40 mg/kg） , chlorpromazine significantly decreased the fecal frequency and water from（ 81 ± 15 ） %, （60 ± 13 ） % to （ 33 ± 21 ） % , （ 25 ± 27 ） % （ P 〈 0.05 ） ; the corresponding colonic cytokines and inflammatory mediators were significantly increased, which is associated with increased protein expressions of iNOS, COX - 2, NF - KB compared with normal control rats from （ 100 ± 11 ） %, （ 100 ± 9 ） %, （ 100 ± 12 ） % to （ 289 ± 19 ） %, （ 311 ± 28 ） %, （ 209 ± 18 ） % （P 〈 0.05 ）. Conclusion Chronic use of chlorpromazine leads to colon inflammation through NF - KB activating iNOS/COX - 2 pathway. Chlorpromazine is also widely used in Long - term hospitalization and economic difficulties of the patients.