平胃胶囊对肝郁脾虚腹泻型肠易激综合征大鼠脑肠肽的影响

Effect of Pingwei capsule on cerebral enteric peptide in irritable bowel syndrome rats with liver stagnation and spleen deficiency

目的研究平胃胶囊对肝郁脾虚腹泻型肠易激综合征(IBS-D)大鼠相关脑肠肽因子含量的影响,基于脑肠轴探讨其可能的作用机制。方法将48只Wistar♂大鼠适应性饲养7 d后,随机均分为正常对照组、模型组、匹维溴铵组、平胃胶囊组(低、中、高剂量平胃胶囊)。除正常对照组外,其余各组的大鼠均采用乙酸灌肠+夹尾应激+束缚限制活动+饥饱失常的方法制备肝郁脾虚证的IBS病证结合模型,共造模21 d后,造模成功后进行给药,以2.5 mg·mL^(-1)匹维溴铵灌胃,平胃胶囊分别按临床等效剂量2、1、0.5倍给药。正常对照组、模型组给予等量生理盐水以0.01 mL·g^(-1)灌胃,连续14 d。造模后及给药结束后分别测定各组大鼠的一般情况、腹泻情况、结肠排珠、腹壁撤退等行为学指标进行模型评价以及药物的可能作用机制。并采用酶联免疫法检测大鼠血清中钙素基因相关肽(CGRP)、血管活性肠肽(VIP)、P物质(SP)、神经肽Y(NPY)的表达情况。结果与正常对照组比较,模型组大鼠的体重明显下降,腹泻指数显著上升,结肠排珠潜伏时间缩短,AWR评分增高,血清中CGRP、VIP、SP的含量显著升高,NPY的含量显著降低;与模型组比较,治疗后各组大鼠的体重有所上升,腹泻指数、结肠动力及肠道敏感性均有所好转,具显著性差异;血清中CGRP、VIP、SP的水平降低,NPY的水平升高;结肠组织未见明显的病理学改变。结论平胃胶囊的作用机制可能与升高血清中NPY的含量,降低SP、VIP、CGRP的含量有关,同时可改善肝郁脾虚型IBS-D模型大鼠的腹泻状况,恢复大鼠体重,抑制大鼠结肠运动,降低肠道高敏感性,减低疼痛阈值,从而达到治疗IBS-D的作用。

OBJECTIVE To investigate the possible mechanism of action of Pingwei capsule(PWC)on diarrhea irritable bowel syndrome(IBS-D)rat model.METHODS After adaptively feeding 48 rats for 1 week,they were randomly divided into normal control group(NC),model group,Pivonium bromide group,PWC low dose group,PWC medium dose group,PWC high dose group.All groups except NC were used acetic acid enema+tail-clamping stress+restraint restriction activity+anorexia of hunger and satiety to prepare the combined model of IBS disease and syndrome of liver stagnation and spleen deficiency syndrome,which was continuously modeled for 21 days.After the model was successfully administered,Piveconium bromide was given 2.5 mg·mL^(-1) and PWC was given 2,1,0.5 times the clinical equivalent dose.The NC group and model group were given the same amount of normal saline for 0.01 mL·g^(-1) to the stomach for 14 consecutives.The general condition,diarrhea,colon bead drainage and abdominal wall withdrawal of rats in each group were evaluated and the effect of the expression of CGRP,VIP,SP,NPY in rat serum was detected by ELISA.RESULTS Compared to NC group,the body weight of model rats decreased significantly,the diarrhoea index increased significantly,the colon bead latency shortened,the AWR score increased,CGRP,VIP,SP increased in serum significantly,and NPY decreased significantly.After treatment,compared to model group,body weight increased in each group,diarrhea index,colon motility and intestinal sensitivity improved with significant difference.CGRP,VIP,SP levels in serum decreased,NPY levels increased.There was no obvious pathological change in colon tissue.CONCLUSION The mechanism of action of PWC may be related to the increase of serum NPY content and the reduction of serum SP and VIP content.It can improve the diarrhea status of IBS-D model rats with liver stagnation and spleen deficiency,restore the weight of rats,inhibit the colonic movement of rats,reduce the intestinal hypersensitivity and lower the pain threshold,so as to play the role of treating IBS-D.