辽宁中医药大学学报

目的 探究首荟通便胶囊对功能性便秘模型大鼠的疗效及其潜在作用机制。方法 将60只SD大鼠按随机原则分为6组，包括空白组、模型组、对照组和首荟通便胶囊低剂量组(75 mg·kg^-1)、中剂量组(150 mg·kg^-1)、高剂量组(300 mg·kg^-1)。对模型组和给药组以盐酸洛哌丁胺灌胃构建功能性便秘模型，造模成功后各给药组按剂量灌胃14 d。对大鼠粪便样本进行粪便含水量测定，采用实时荧光定量反转录聚合酶链反应(real-time quantitative reverse transcription PCR,RT-qPCR)对海马区环腺苷酸依赖性蛋白激酶(cAMP-dependent protein kinase,PKA)和环腺苷酸应答元件结合蛋白(cAMP-response element binding protein,CREB)基因的信使核糖核酸(messenger RNA,mRNA)进行转录水平分析，以蛋白质印迹(Western blot,WB)法分析海马区PKA与CREB蛋白表达量，采用免疫组织化学技术对结肠组织中血管活性肠肽(vasoactive intestinal peptide,VIP)与5-羟色胺(5-hydroxytryptamine,5-HT)的表达情况进行检测。结果 首荟通便胶囊显著改善洛哌丁胺诱导的功能性便秘大鼠症状、促进肠道运动，具体表现为提高粪便含水量、缓解便秘病理状态，增强结肠组织VIP与5-HT阳性表达强度，上调海马体PKA和CREB的mRNA及蛋白表达水平。结论 首荟通便胶囊或通过调节脑-肠轴相关分子表达改善功能性便秘大鼠肠道功能，作用机制可能与激活PKA/CREB信号通路有关。

Objective This study focuses on exploring the therapeutic effects of Shouhui Tongbian Capsules (首荟通便胶囊)on rats with functional constipation and its potential mechanism of action. Methods Sixty SD rats were randomly allocated into six groups:blank control,model control,positive control,and three Shouhui Tongbian Capsules treatment groups(low-dose:75 mg·kg^-1,mediumdose:150 mg·kg^-1,high-dose:300 mg·kg^-1). Functional constipation models were established in the model and treatment groups via intragastric administration of loperamide hydrochloride. After successful model induction,the treatment groups received their respective doses of Shouhui Tongbian Capsules for 14 days. The fecal moisture content of rat fecal samples were determined,the messenger RNA(mRNA)transcription levels of cAMP-dependent protein kinase(PKA)and cAMP-response element binding protein(CREB)genes in the hippocampus were analyzed by using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR),Western blot(WB) method was applied to analyze the protein expression levels of PKA and CREB in the hippocampus,immunohistochemical technique was used to evaluate the expression of vasoactive intestinal peptide(VIP)and 5-hydroxytryptamine(5-HT)in colonic tissues. Results Shouhui Tongbian Capsules significantly alleviated symptoms and promoted intestinal motility in rats with loperamide-induced functional constipation. Specifically,it increased fecal water content,ameliorated the pathological state of constipation,enhanced the positive expression intensity of VIP and 5-HT in colon tissue,and up-regulated the mRNA and protein expression levels of PKA and CREB in the hippocampus. Conclusion Shouhui Tongbian Capsules improves intestinal function in constipated rats potentially by modulating the expression of molecules related to the brain-gut axis,the underlying mechanism may be associated with the activation of the PKA/CREB signaling pathway.