三七总皂苷抑制动脉粥样硬化与改善肠道屏障完整性的作用研究  

Effect of Panax Notoginseng Saponins on Inhibiting Atherosclerosis and Improving Intestinal Barrier Integrity

作　　者：张自龙 熊敏琪[1,2] 崔金刚[1,2] 杜霄烨[1,2] 徐静 陈瑜[1,2] 张腾[1,2] ZHANG Zilong;XIONG Minqi;CUI Jingang;DU Xiaoye;XU Jing;CHEN Yu;ZHANG Teng(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine.Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Clinical Institute of Integrative Chinese and Western Medicine of Shanghai Academy of Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海市中医药研究院中西医结合临床研究所,上海200437

出　　处：《世界科学技术-中医药现代化》2024年第2期390-399,共10页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会青年科学基金项目(81903835):三七总皂苷对动脉粥样硬化伴急性心肌缺血的综合干预效应与miRNA调控机制研究,负责人:熊敏琪。

摘　　要：目的探讨三七总皂苷(Panax notoginseng saponins,PNS)抑制动脉粥样硬化(Atherosclerosis,AS)和改善肠道屏障的效应。方法以高脂饮食喂养的载脂蛋白基因E敲除(ApoE-/-)小鼠作为AS模型,C57BL/6J小鼠给与普通饮食作为正常组,24只ApoE-/-小鼠给与高脂饮食并按随机数字分为模型组,PNS低剂量给药组和PNS高剂量给药组。PNS低剂量和高剂量组小鼠分别给予50 mg·kg^(-1)·d^(-1)和250 mg·kg^(-1)·d^(-1)PNS灌胃,模型组和正常组小鼠给予同等体积生理盐水。8周后通过HE染色和油红O染色观察小鼠主动脉根部斑块病理改变和脂质沉积情况;通过MCP-1和CD68免疫组化染色观察小鼠主动脉根部巨噬细胞的浸润情况;通过HE染色和阿利新蓝染色观察小鼠回肠病理损伤情况;通过Cingulin免疫荧光染色观察小鼠回肠紧密连接完整性;采用Real-time qPCR法分析小鼠回肠紧密连接蛋白ZO(Zonula Occludens,ZO)-1、Claudin-1 mRNA表达水平;通过ELISA法检测小鼠血清炎症因子TNF-α和IL-1β含量。结果相较于正常组小鼠,模型组小鼠主动脉根部可见明显的AS斑块和脂质沉积,回肠病理损伤明显,回肠绒毛长度变短,杯状细胞数量减少,回肠紧密连接蛋白表达显著下调,肠道屏障受损,血清炎症因子显著升高,主动脉根部巨噬细胞浸润明显。与模型组相比,PNS给药组小鼠主动脉根部斑块的大小及斑块内坏死核心的面积显著减小(P<0.05),主动脉根部脂质沉积显著减少(P<0.01)。回肠损伤显著减轻,回肠绒毛显著增长(P<0.05),杯状细胞数量显著增多(P<0.05),回肠紧密连接蛋白Cingulin及Claudin-1显著增加(P<0.05),显著减轻肠道屏障损伤,血清炎症因子TNF-α和IL-1β显著降低(P<0.05),主动脉根部巨噬细胞浸润显著减少(P<0.05)。结论PNS具有改善肠道屏障,减少炎症反应,抑制AS进展的作用。Objective To explore the effects of Panax notoginseng saponins(PNS)on inhibiting Atherosclerosis(AS)and improving intestinal barrier function.Methods Twenty four apolipoprotein E knockout(ApoE-/-)mice were randomly divided into three groups:high-fat high-cholesterol control diet(HFD),HFD with PNS(50 mg·kg^(-1)·d^(-1),PNS-L),or(250 mg·kg^(-1)·d^(-1),PNS-H).C57BL/6J mice were included as the normal control and fed on a standard chow diet.PNS-L or PNS-H was administered orally to the mice by gavage once a day for 8 weeks,while the C57 and HFD group mice received an equal volume of saline.At the end of the experiment,hematoxylin and eosin(HE)and oil red O staining were performed to characterize the gross morphology and lipid deposition in the aorta root.The immunohistochemical analysis of MCP-1 and CD68 were used to observe the infiltration of macrophages in the aortic root.The pathological injury of ileum was observed by HE and Alcian blue staining.The immunofluorescence staining of Cingulin was used to observe the integrity of tight junctions in the ileum.The mRNA expression of tight junction proteins ZO-1 and Claudin-1 was analyzed by Real time-PCR.The serum levels of TNF-αand IL-1βwere detected by ELISA.Results The HFD mice had lots of lesion area and lipid deposition area in the aorta root compared with C57 mice.Meanwhile,HFD-induced histological changes in ileums,manifested as the shallowness of villi length and the decline of goblet cell numbers.In addition,the expression of intestinal tight junction protein was decreased and the intestinal barrier was impaired in the HFD-fed group.The serum inflammatory cytokines were significantly increased,and there were more infiltration of macrophages in the aortic root.Compared with the HFD group,PNS treatment had a significant reduction in lesion area,necrotic core area and lipid deposition area in the aortic root(P<0.05).Furthermore,PNS treatment attenuated the pathological alterations in the ileum,the villi length and the goblet cell numbers were significantly i

关 键 词：动脉粥样硬化 三七总皂苷 肠道屏障 炎症反应 

分 类 号：R285.5[医药卫生—中药学]