摘要
目的研究利那洛肽(linaclotide)联合普芦卡必利(prucalopride)对便秘型肠易激综合征(IBS-C)大鼠脑肠肽和胃肠激素分泌的影响。方法选取50只SPF级SD大鼠,随机选取其中10只大鼠设为正常对照组(Con组);其余40只大鼠采用冰水灌胃法建立IBS-C模型后,将其随机分为IBS-C组、利那洛肽组(Lina组)、普芦卡必利组(Pruca组)和利那洛肽联合普芦卡必利组(Lina+Pruca组),每组10只大鼠;各组给药干预。记录各组的24h粪便粒数并测定24h粪便含水量,采用腹部回缩反射(AWR)评分测定各组的内脏敏感度,活性炭混悬液灌胃法测定各组的小肠推进率,H-E染色法观察各组肠黏膜组织病理形态学变化,蛋白质印迹法检测各组结肠组织中相关蛋白的表达水平。结果与Con组比较,IBS-C组的24 h粪便粒数及含水量均显著减少,20、40、60、80 mmHg压力下的AWR评分均显著增高,小肠推进率显著降低(P均<0.05);IBS-C组的结肠黏膜腺体排列较整齐,肌层有断裂,黏膜层可见少量炎症细胞浸润;IBS-C组的结肠组织中5-羟色胺(5-HT)、血管活性肠肽(VIP)、生长抑素(SS)蛋白的表达水平均显著升高,P物质(SP)、胃动素(MOT)蛋白的表达水平均显著降低(P均<0.05)。与IBS-C组比较,Lina组、Pruca组和Lina+Pruca组的24 h粪便粒数及含水量均显著增多(P均<0.05);Lina组、Pruca组和Lina+Pruca组的20、40、60、80 mmHg压力下的AWR评分均显著降低,小肠推进率均显著升高(P均<0.05);Lina组、Pruca组和Lina+Pruca组的肠黏膜组织形态学均有缓解;Lina组、Pruca组和Lina+Pruca组的结肠组织中5-HT、VIP、SS蛋白的表达水平均显著降低,SP、MOT蛋白的表达水平均显著升高(P均<0.05);Lina+Pruca组的上述指标改善均较Lina组和Pruca组显著(P均<0.05)。结论利那洛肽联合普芦卡必利能有效改善IBS-C模型大鼠脑肠肽和胃肠激素的分泌。
Objective An attempt is made in this paper to study the effects of linaclotide in combination with prucalopride on the secretion of brain-gut peptides and gastrointestinal hormones in rats with constipated irritable bowel syndrome(IBS-C).Methods Fifty SPF grade SD rats were selected,of which 10 were randomly assigned to the normal control group(Con group).After establishing the IBS-C model using ice water gavage,the remaining 40 rats were randomly assigned to the IBS-C group,the linalopide group(Lina group),the pruca group(Pruca group),and the linalopide combined with pruca group(Lina+Pruca group),with 10 rats in each group.Each group received medication intervention.The 24 h fecal particle count and fecal water content of each group were recorded.The visceral sensitivity of each group was measured using abdominal retraction reflex(AWR)score.The small intestine propulsion rate of each group was measured by gavage with activated carbon suspension.The pathological and morphological changes of the intestinal mucosa tissue in each group were observed using H-E staining.The expression levels of related proteins in the colon tissue in each group were detected using western blotting.Results Compared with the Con group,the 24 h number of fecal particles and fecal water content of rats in the IBS-C group are significantly reduced,the AWR scores at pressures of 20,40,60,and 80 mmHg are significantly increased,while the small intestine propulsion rate is significantly reduced(P<0.05).The arrangement of colonic mucosal glands in the IBS-C group is relatively neat,with muscle layer breaks and a small amount of inflammatory cell infiltration in the mucosal layer.The expression levels of 5-HT,VIP,and SS proteins in the colon tissue of the IBS-C group are significantly increased,while the expression levels of SP and MOT proteins are significantly reduced(P<0.05).Compared with the IBS-C group,the 24 h number of fecal particles and fecal water content of rats in the Lina group,the Pruca group,and the Lina+Pruca group are significa
作者
王影
刘畅
张婉
谷云
孙丹
崔文丽
任晓华
WANG Ying;LIU Chang;ZHANG Wan;GU Yun;SUN Dan;CUI Wenli;REN Xiaohua(Department of Pharmacy,Shijiazhuang People’s Hospital,Shijiazhuang 050011,China;Department of Pharmacy,the Fourth People’s Hospital of Hengshui City,Hengshui 053000,China)
出处
《国际消化病杂志》
CAS
2023年第3期177-183,共7页
International Journal of Digestive Diseases
基金
河北省医学科学研究计划项目(20221701)。
关键词
便秘型肠易激综合征
利那洛肽
普芦卡必利
脑肠肽
胃肠激素
Irritable bowel syndrome with constipation
Linaclotide
Prucalopride
Brain-gut peptide
Gastrointestinal hormone
