宁肠汤基于p38MAPK通路治疗腹泻型肠易激综合征的机制研究OA

Objective To investigate the mechanism of Ningchang Decoction in the treatment of diarrhea-predominant irritable bowel syndrome(IBS-D)via regulating the p38 mitogen-activated protein kinase(p38MAPK)signaling pathway.Methods Forty male Sprague-Dawley(SD)rats were randomly divided into 5 groups(n=8 per group):the control group,model group,high-dose Ningchang Decoction group(26.26 g/kg),low-dose Ningchang Decoction group(13.13 g/kg),and pinaverium bromide group(15.75 mg/kg).After 7 days of adaptive feeding,the IBS-D rat model was established by 4％acetic acid enema combined with chronic restraint stress(administered in stages from day 7 to day 23).From the 10th day of modeling,intragastric intervention was performed for 14 consecutive days:the high-and low-dose Ningchang Decoction groups were given concentrated aqueous extract of Ningchang Decoction,the pinaverium bromide group was given pinaverium bromide suspension,and the control group and model group were given normal saline.After the intervention,the Bristol Stool Form Scale score and abdominal withdrawal reflex(AWR)score were used to evaluate the fecal characteristics and visceral sensitivity of rats,respectively.Hematoxylin-eosin(HE)staining was performed to observe the pathological changes of colon tissues.The mRNA expression levels of p38MAPK pathway-related genes[p38MAPK,mitogen-and stress-activated protein kinase 1(MSK1),cAMP response element-binding protein(CREB)]in colon tissues were detected by reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR).The ratios of phosphorylated p38(p-p38)to total p38,phosphorylated CREB(p-CREB)to total CREB,and phosphorylated MSK1(p-MSK1)to total MSK1 were determined by Western blot.Results Compared with the control group,the model group showed significantly increased Bristol Stool Form Scale score and visceral sensitivity,as well as upregulated p38MAPK pathway-related gene and protein levels(all P＜0.05).Compared with the model group,the low-dose Ningchang Decoction group and pinaverium bromide group had significantly decreased Bristol scores;all treatment groups exhibited significantly increased water infusion volume required for AWR response,downregulated mRNA and protein expressions of p38MAPK pathway-related genes(all P＜0.05),and alleviated pathological injury of colon tissues.Conclusion Ningchang Decoction can ameliorate intestinal symptoms of IBS-D by inhibiting the p38MAPK pathway and downregulating the expression of MSK1 and CREB.The therapeutic efficacy of low-dose Ningchang Decoction is comparable to that of pinaverium bromide,while high-dose Ningchang Decoction has limited regulatory effect on partial symptoms.