温肾健脾调枢方对腹泻型肠易激综合征大鼠的治疗作用及机制

Effect and mechanism of Wenshen Jianpi Tiaoshu Recipe on diarrhea-predominant irritable bowel syndrome rats

目的观察中药温肾健脾调枢方干预对腹泻型肠易激综合征(diarrhea-predominant irritable bowel syndrome,IBS-D)大鼠磷酸化cAMP应答元件结合蛋白(pCREB)及下游即刻早期基因Arc、c-fos表达的影响。方法将40只Wistar大鼠适应性喂养5 d后,采用随机数字表法分为正常组(NG)、模型组(MG)、中药温肾健脾调枢方高剂量组(ZHG)、中药温肾健脾调枢方中剂量组(ZMG)和中药温肾健脾调枢方低剂量组(ZLG)5组,各8只。MG组、ZHG组、ZMG组和ZLG组均采用番泻叶灌胃法+避水应激实验建立IBS-D大鼠模型,ZHG组、ZMG组、ZLG组按高、中、低剂量给予温肾健脾调枢方灌胃,MG组、NG组给予生理盐水灌胃,1次/d,连续10 d。观察比较各组大鼠一般情况、体质量变化、排便粒数、内脏敏感性和组织病理学,免疫组化检测结肠组织中pCREB、Arc、c-fos表达。结果治疗结束后,ZHG组和ZMG组大鼠体质量高于MG组(P<0.05);ZHG组、ZMG组、ZLG组大鼠1 h内排便粒数低于MG组(P<0.05);ZHG组大鼠腹壁撤退反射(AWR)评分低于MG组(P<0.05);MG组和ZLG组组织病理学观察可见黏膜轻度水肿;ZHG组、ZMG组和ZLG组大鼠结肠组织pCREB表达低于MG组(P<0.05);ZHG组、ZMG组大鼠结肠组织Arc、c-fos表达低于MG组(P<0.05)。结论温肾健脾调枢方能够增加IBS-D大鼠体质量、减少排便粒数、降低内脏敏感性,其作用机制可能是通过调控结肠组织中pCREB、Arc和c-fos的表达实现。

Objective To observe the effect of Wenshen Jianpi Tiaoshu Recipe on the expression of pCREB,Arc and c-fos in colon tissue of diarrhea-predominant irritable bowel syndrome(IBS-D)rats.Methods After adaptive feeding for 5 days,40 Wistar rats were divided into 5 groups with random number table,which were normal group(NG),model group(MG),Chinese medicine treatment groups of high dosage,medium dosage and low dosage(ZHG,ZMG,ZLG),with 8 rats in each group.IBS-D rat models were established by the method of avoiding water stress experiment and senna leaf garage in MG,ZHG,ZMG and ZLG.After modeling,the Chinese medicine treatment groups(ZHG,ZMG,ZLG)were given with high,medium and low doses of Wenshen Jianpi Tiaoshu Recipe by gavage respectively,MG and NG were given normal saline respectively by gavage,all once a day and for10 days.The general conditions,body mass changes,number of defecation pellets,visceral sensitivity and histopathology were observed.Immunohistochemistry was used to detect the expression of pCREB,Arc and c-fos in colon tissue.Results After treatment,the body mass of ZHG and ZMG was significantly higher than that of MG(P<0.05);the number of defecation pellets within 1 hour of ZHG,ZMG and ZLG was significantly less than that of MG(P<0.05);the abdominal wall withdrawal reflex(AWR)scores of ZHG was lower than that of MG(P<0.05);Histopathological observation showed mild edema in MG and ZLG mucosa;The expression of pCREB in colon tissue of ZHG,ZMG and ZLG was lower than that of MG(P<0.05);the expression of Arc and c-fos in colon tissue of ZHG and ZMG was lower than that of MG(P<0.05).Conclusion Wenshen Jianpi Tiaoshu Recipe can increase the body weight,reduce the number of defecation granules and lower visceral sensitivity of IBS-D rats.Its therapeutic mechanism may be related with the regulation of the expression of pCREB,Arc and c-fos in colon tissue.