理气通便方对气滞证慢传输型便秘大鼠肠道动力及肠道菌群的影响  

Effects of Liqi Tongbian Decoction on intestinal motility and intestinal flora in rats with slow transit constipation with Qi stagnation pattern

作　　者：刘启鸿[1,2] 骆云丰 柯晓[1,2] 胡露楠 严锦贤[3] 方文怡 赵培琳 LIU Qihong;LUO Yunfeng;KE Xiao;HU Lunan;YAN Jinxian;FANG Wenyi;ZHAO Peilin(Department of Spleen and Stomach,the Second People's Hospital,Fujian University of TraditionalChinese Medicine,Fuzhou,350003,China;Fujian Traditional Chinese Medicine Spleen and Stomach Clinical Medical Research Center;Fujian Provincial Key Laboratory of Chinese Medicine Preparation for Medical Institutions,Fujian University of Traditional Chinese Medicine)

机构地区：[1]福建中医药大学附属第二人民医院脾胃病科,福州350003 [2]福建省中医脾胃临床医学研究中心 [3]福建省医疗机构中药制剂重点实验室(福建中医药大学)

出　　处：《中国中西医结合消化杂志》2023年第11期847-854,共8页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：国家自然科学基金面上项目(No:82274282);福建省自然科学基金面上项目(No:2021J01878)。

摘　　要：目的:观察理气通便方对气滞证慢传输型便秘(slow transit constipation,STC)大鼠肠道动力及肠道菌群的影响。方法:以36只Wistar大鼠为研究对象,根据随机数字表法选取6只为正常组,其余大鼠采用“洛哌丁胺混悬液+夹尾刺激”复制气滞证STC大鼠模型。造模成功后,将大鼠随机分为气滞证STC模型组、琥珀酸普芦卡必利片组和理气通便方低、中、高剂量组,每组6只。正常组与气滞证STC模型组给予等容积的蒸馏水灌胃,琥珀酸普芦卡必利片组给予0.18mg/(kg·d)混悬液灌胃,理气通便方低、中、高剂量组分别用5.15、10.30和20.60g/kg药液灌胃。通过粪便数量、粪便含水量、小肠推进率评价理气通便方的治疗效果。采用免疫组化方法检测大鼠结肠组织中Cajal间质细胞(Cajal interstitial cell,ICC)、5-HT、5-HT3受体(5-HT3R)及5-HT4受体(5-HT4R)蛋白表达水平。采用气相色谱-质谱联用法测定短链脂肪酸(short-chain fatty acids,SCFAs)含量的变化。采用16SrDNA高通量测序分析肠道菌群的变化。结果:与正常组比较,气滞证STC模型组大鼠的粪便数量减少、粪便含水量和小肠推进率均下降(P<0.05),结肠组织中ICC、5-HT、5-HT3R及5-HT4R蛋白表达水平均降低(P<0.05),肠道菌群的丰度和多样性显著下降(P<0.05),毛螺菌属、梭菌属丰度下降(P<0.05),粪球菌属、克雷伯菌属丰度增加(P<0.05),粪便中SCFAs含量降低(P<0.05);与气滞证STC模型组比较,给药组大鼠粪便数量及含水率均增加(P<0.05),小肠推进率除理气通便方低剂量组差异无统计学意义外,其他均差异有统计学意义(P<0.05);结肠组织中ICC、5-HT、5-HT3R及5-HT4R蛋白表达水平升高,其中除了理气通便方低剂量组5-HT蛋白表达及琥珀酸普芦卡必利片组ICC、5-HT、5-HT3R蛋白表达水平差异无统计学意义外,其余均差异有统计学意义(P<0.05);琥珀酸普芦卡必利片组与理气通便方中、高剂量组能够显著提高Objective:To investigate the effects of Liqi Tongbian Decoction on intestinal motility and intestinal flora in rats with slow transit constipation(STC)with Qi stagnation pattern.Methods:Thirty-six Wistar rats were selected according to the random number table method,and 6rats were selected as the normal group,and the rest of the rats were used to replicate the STC rat model of Qi stagnation pattern by using"loperamide suspension and tail clamping stimulation".After successful modelling,the rats were randomly divided into the STC model group,the prucalopride succinate tablet group,and the low,medium and high dose groups of the formula,with 6rats in each group.The normal group and the STC model group were given equal volumes of distilled water,the prucalopride succinate tablet group was given 0.18mg/(kg·d)suspension by gavage,and the low,medium and high dose groups of the formula were given 5.15g/kg,10.30g/kg and 20.60g/kg by gavage,respectively.The therapeutic efficacy of the formula was evaluated by the water content of faeces and the propulsion rate of small intestine,and the protein expression levels of murine Cajal interstitial cells(ICC),serotonin(5-HT),serotonin 3receptor(5-HT3R)and serotonin 4receptor(5-HT4R)were detected by immunohistochemistry in colon tissues,and the content of short-chain fatty acids(SCFAs)was measured by gas chromatography-mass spectrometry(GCMS).SCFAs content changes,and 16SrDNA high-throughput sequencing was used to analyse the changes in intestinal flora.Results:Compared with the normal control group,rats in the STC model group with Qi stagnation pattern showed a decrease in the number of faeces,a significant decrease in the water content of faeces and the rate of small intestinal propulsion(P<0.05),a significant decrease in the levels of expression of the 5-HT,5-HT3R and 5-HT4Rproteins in the colonic tissues(P<0.05),and a significant decrease in abundance and diversity of intestinal flora(P<0.05),with a increase in the abundance of Trichoderma spp,Clostridium spp.decreased in abun

关 键 词：理气通便方 肠道菌群 短链脂肪酸 CAJAL间质细胞 5-HT 气滞证慢传输型便秘 

分 类 号：R256.35[医药卫生—中医内科学]