吴茱萸碱对大鼠结肠运动的影响

Effect of Evodiamine on the Motility of Colon in Rats

目的:初步探讨吴茱萸碱对大鼠结肠运动的影响及其可能机制。方法:SD大鼠随机分为对照组和给药组,给药组给予腹腔注射吴茱萸碱2mg/kg,对照组腹腔注射等体积溶剂。采用蛋白印迹法和免疫组织化学方法分别对胆囊收缩素1受体(CCK1R)在结肠的表达进行定量和定位分析,使用生物机能实验系统记录两组肌条自发性收缩活性。结果:给药组大鼠8,12,24h排便量、结肠肌条收缩幅度均低于对照组(P<0.001),而4h排便量两组间的差异无统计学意义(P>0.05);免疫组织化学结果显示,CCK1R在结肠全层皆有弥散表达,但肌层表达最多,且给药组表达较对照组明显;蛋白印迹实验结果表明,与对照组相比,给药组大鼠结肠CCK1R表达上调(P<0.05)。结论:吴茱萸碱可抑制结肠运动,并可诱导结肠CCK1R的表达,为进一步开展治疗肠道动力紊乱的相关药物研究提供一定的理论基础。

Objective： To study the effect and mechanisms of evodiamine on the colonic mobility, and provide theory for exploring clinically effective drug for the therapy of functional gastroenterolog- ical disease. Methods： The SD rats were randomly divided into two groups： control group and drug treatment group. The drug treatment group were injected with evodiamine by 2 mg/kg in- traperitoneally, while the control group were intraperitoneally injected with the same volume of vehicle solution. Immunohistochemistry and Western blot were performed on rat colonic samples to detect the distribution and expression of CCK1R, and the organ bath recordings were used to test the colonic motility. Results： Fecal pellets and contractile activties of the colonic strips de- creased in the drug treatment group as compared with the control group at the end of 8 h, 12 h, and 24 h （P〈0.05）, while fecal pellets at 4 h between the two groups had no statistical differ- ence. The results of immunohistochemistry showed that CCK1R was strongly expressed in the circular and longitudinal smooth muscle cells and myenteric plexus neurons in the drug treatmentgroup, while in the control group CCKIR was expressed weakly. In addition, The results of Western blot represented that, the expression of CCKIR in the drug treatment group was up-reg- ulated when compared with the control group （P〈0.05）. Conclusion： Evodiamine inhibits the colonic mobility and induces CCK1R expression of the colon, which may provide theoretical basis for further exploring drugs for the therapy of intestinal dysmotility.