文献类型：期刊文献

中文题名：益气活血通便方对慢传输型便秘大鼠的治疗作用及机制

英文题名：Therapeutic Effect and Mechanism of Yiqi Huoxue Tongbian Prescription on Slow Transit Constipation in Rats

作者：李硕[1,2,3];杨晓玲[1];刘书斌[4];王本欢[1];郑贵森[1];段国建[1,2,3];赵林华[5];杨秀娟[1,2,3];仝小林[5]

第一作者：李硕

机构：[1]甘肃中医药大学,兰州730000;[2]西北中藏药省部共建协同创新中心,兰州730000;[3]陇药产业创新研究院,兰州730000;[4]甘肃省中医院,兰州730050;[5]中国中医科学院广安门医院,北京100053

第一机构：甘肃中医药大学

年份：2023

卷号：29

期号：23

起止页码：16

中文期刊名：中国实验方剂学杂志

外文期刊名：Chinese Journal of Experimental Traditional Medical Formulae

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金项目(81960713);甘肃省高等学校创新基金项目(2021A-079);甘肃省中药原料质量建设项目(998/9983999916);甘肃省中医药科研课题项目(GZKZ-2021-7);甘肃省科技厅项目(自然科学基金18JR3RA201,基础研究创新群体21JR7RA569,青年科技基金20JR10RA331);甘肃省教育厅项目(2121CYZC-21,2021B-157)。

语种：中文

中文关键词：慢传输型便秘;益气活血通便方;水通道蛋白;神经递质;肠道菌群

外文关键词：slow transit constipation;Yiqi Huoxue Tongbian prescription;aquaporin;neurotransmitters;intestinal flora

摘要：目的:探讨益气活血通便方对慢传输型便秘(STC)大鼠的治疗作用及机制。方法:采用盐酸洛哌丁胺灌胃法建立STC大鼠模型,设定正常组、模型组、莫沙必利组、益气活血通便方低、中、高剂量组(3.51、7.02、14.04 g·kg^(-1))给药后观察各组大鼠一般体征变化、计算粪便含水率及肠道推进率;采用苏木素-伊红染色观察结肠组织黏膜炎症改变;采用酶联免疫吸附测定法检测各组大鼠结肠P物质(SP)、血管活性肠肽(VIP)含量;采用免疫组织化学法和蛋白免疫印迹法检测大鼠结肠组织水通道蛋白(AQP)3、AQP4、AQP8和c-Kit蛋白灰度值,通过16S r RNA高通量测序检测肠道菌群变化。结果:经过益气活血通便方给药治疗10 d后,与模型组比较,益气活血通便方不同剂量组和莫沙必利组大鼠的粪便含水率和肠道推进率均显著增加(P<0.01)。与模型组比较,益气活血通便方中、高剂量组和莫沙必利组大鼠结肠无明显黏膜炎症改变,杯状细胞排列较规整无断裂、数量较多。益气活血通便方中、高剂量组和莫沙必利组血清中SP含量明显升高(P<0.05,P<0.01),VIP明显降低(P<0.05);益气活血通便方中、高剂量组AQP3、AQP4、AQP8的蛋白表达量显著降低(P<0.01),c-Kit的蛋白表达量显著增加(P<0.01);不同剂量组大鼠粪便菌群observed pecies、Chao1、ACE指数及Shannon、PD whole tree有升高的趋势,但差异无统计学意义。主成分分析(PCA)表明正常组与益气活血通便方高、中剂量组的距离较近,证实经过益气活血通便方高、中剂量给药后,其肠道菌群与正常组粪便菌群保持一致。结论:益气活血通便方可改善STC大鼠排便情况,其机制可能与减少AQP3、AQP4、AQP8对肠道内水分的吸收,升高c-Kit蛋白从而上调Cajal间质细胞的数量及分布及调节结肠组织内的菌群平衡等多种机制有关。
Objective:To explore the therapeutic effect and mechanism of Yiqi Huoxue Tongbian prescription on slow transit constipation(STC)in rats.Method:The rat model of STC was established by gavage of loperamide hydrochloride.Rats were assigned into control,model,mosapride,low-,medium-,and high-dose(3.51,7.02,and 14.04 g·kg^(-1),respectively)Yiqi Huoxue Tongbian prescription groups.The changes of general signs,fecal moisture content,and intestinal propulsion rate were measured after model establishment and drug administration.The colonic mucosal changes were observed by hematoxylin eosin staining.Enzymelinked immunosorbent assay was employed to determine the content of substance P(SP)and vasoactive intestinal peptide(VIP)in the colon of rats in each group.The gray values of aquaporin(AQP)3,AQP4,AQP8,and c-Kit in rat colon tissue were measured by immunohistochemistry and Western blot,and the changes of intestinal flora were detected by 16S rRNA high-throughput sequencing.Result:Compared with the model group,10 days of treatment with Yiqi Huoxue Tongbian prescription increased the fecal moisture content and intestinal propulsion rate(P<0.01).The medium-and high-dose Yiqi Huoxue Tongbian prescription groups and the mosapride group showed no obvious mucosal inflammation and neat arrangement of goblet cells with a large number in the colon tissue.Moreover,the three groups showed increased SP content(P<0.01)and decreased VIP content(P<0.01)in the serum.The medium-and high-dose Yiqi Huoxue Tongbian prescription groups showed down-regulated protein levels of AQP3,AQP4,and AQP8(P<0.01)and up-regulated protein level of c-Kit(P<0.01).The drug administration groups presented slightly increased observed species,Chao1,ACE,and Shannon,Simpson,and PD whole tree.The principal component analysis showed that the control group had a short distance with the high-and medium-dose Yiqi Huoxue Tongbian prescription groups,indicating that highand medium-dose Yiqi Huoxue Tongbian prescription can recover the intestinal flora to that in the control group.Conclusion:Yiqi Huoxue Tongbian prescription can alleviate the defecation status of rats with slow transit constipation by down-regulating the expression of AQP3,AQP4,and AQP8 to reduce the absorption of water in the intestine,up-regulating the expression of c-Kit to increase the number and distribution of Cajal interstitial cells,and regulating the balance of flora in the colon tissue.