中药药理与临床2025，Vol.41Issue(11)：57-63,7.
健脾化瘀方调控肠黏膜屏障损伤及肠道菌群紊乱缓解动脉粥样硬化
Mechanism of Jianpi Huayu(健脾化瘀)Prescription in Alleviating Atherosclerosis through Regulation of Intestinal Mucosal Barrier Damage and Intestinal Flora Disturbance
摘要
Abstract
Objective:To investigate the effects and potential mechanisms of Jianpi Huayu(健脾化瘀)Prescription on plaque formation,blood lip-ids,intestinal mucosal barrier,and intestinal flora in mice with atherosclerosis(AS).Methods:The AS model was established by feeding apolipoprotein E gene knockout(ApoE-/-)mice with a high-fat diet for 12 weeks.After 12 weeks of modeling,the mice were randomly divid-ed into the model control group,the positive control group(Atorvastatin,3 mg/kg),and the Jianpi Huayu Prescription groups(14 g/kg,28 g/kg and 56 g/kg).C57BL/6J mice were fed with normal food as the normal control group.Serum and related tissues were collected after 12 weeks of intragastric administration.Oil red O macroscopic staining was used to observe the aortic plaque area of mice,and hematoxylin-e-osin(HE)staining was used to observe the aortic plaques and pathological changes in mice.The levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C)in serum of mice were detected by the automatic biochemical analyzer.The pathological changes of the intestinal mucosal barrier were observed by hematoxylin-eosin(HE),Alcian blue,and wheat germ agglutinin(WGA)staining.The content of lipopolysaccharide(LPS)in serum and colon tissue was detected by en-zyme-linked immunosorbent assay(ELISA).Real-time quantitative fluorescent PCR(qRT-PCR)and Western blot were used to detect pro-tein and mRNA expressions of tight junction proteins ZO-1,Occludin1,Claudin1,and JAM-1 in the colon tissue of mice.High-throughput se-quencing of 16S rRNA in cecal contents was conducted to analyze the changes in intestinal flora.Results:Jianpi Huayu Prescription reduced the generation of foam cells and plaques in the aorta tissue of AS model mice,increased plaque stability,and reduced blood lipid levels.Com-pared with the normal control group,the model control group showed damaged intestinal tissue,reduced thickness of intestinal lamina propria,decreased number of goblet cells and mucin secretion in the mucosal layer,significantly increased LPS levels in serum and cecal contents(P<0.05),elevated contents of TC,TG,and LDL-C in serum(P<0.05),decreased content of HDL-C in serum(P<0.05),down-regulated protein and mRNA expressions of ZO-1,Occludin1,Claudin1,and JAM-1 in colon tissue(P<0.01 or P<0.05),and significantly decreased intestinal bacterial species and diversity indexes such as Chao1 and Observed_otus in the AS group(P<0.05).Compared with those in the model control group,after treatment by Jianpi Huayu Prescription,the intestinal muscularis propria was restored;the number of goblet cells in the mucosal layer was increased,and the level of LPS was decreased(P<0.01 or P<0.05).The protein and mRNA expressions of ZO-1,Oc-cludin1,Claudin1,and JAM-1 in colon tissue were up-regulated significantly(P<0.01 or P<0.05).Compared with those in the normal con-trol group,the Alpha diversity indexes Chao1,Observed_otus,Shannon,and Simpson were significantly reduced in the model control group(P<0.05),and the bacterial groups with higher abundance at the phylum level included Firmicutes and Turicibacter.Compared with those in the model control group,the Alpha diversity index of mice in the Jianpi Huayu Prescription groups was increased significantly(P<0.05),and the bacterial groups with higher abundance at the phylum level were Bacteroidetesother and Muribaculaceae.Conclusion:The Jianpi Huayu Prescription may prevent and treat AS by regulating the intestinal flora composition of AS model mice,improving the intestinal mucosal barrier function,and reducing the release of inflammatory mediator LPS into the blood.关键词
健脾化瘀方/动脉粥样硬化/肠黏膜屏障/肠道菌群/紧密连接蛋白/闭锁小带蛋白-1Key words
Jianpi Huayu(健脾化瘀)Prescription/Atherosclerosis/Intestinal mucosal barrier/Intestinal flora/Tight junction protein/Zonula occludens-1引用本文复制引用
钊浩然,张选明,张志刚,鲜沁赤,王富巧,王睿思..健脾化瘀方调控肠黏膜屏障损伤及肠道菌群紊乱缓解动脉粥样硬化[J].中药药理与临床,2025,41(11):57-63,7.基金项目
青年岐黄学者培养项目[国中医药人教函(2022)256号] （2022）
石河子大学科研项目(编号:ZZZC2023065) （编号:ZZZC2023065）
"天山英才"医药卫生高层次人才培养项目(编号:CZ001223) （编号:CZ001223）
兵团中医临床医学研究中心项目(编号:CZ001233). （编号:CZ001233）
