[关键词]
[摘要]
目的 观察丹蒌片对高脂喂养动脉粥样硬化模型ApoE-/-小鼠的影响,从菌群失调诱发炎症角度探讨丹蒌片抗动脉粥样硬化的作用机制。方法 采用C57BL/6J野生型小鼠作为对照,高脂喂养ApoE-/-小鼠24周后随机分为模型组、丹蒌片组,连续ig给药8周后取血测定血脂水平;ELISA法检测血清中脂多糖(LPS)水平;动脉大体油红O及主动脉窦HE染色观察斑块形成;粪便16 S rRNA扩增子测序检测肠道菌群;GC-MS法检测短链脂肪酸;实时荧光定量PCR法检测炎症因子肿瘤坏死因子-α(TNF-α)、细胞间黏附分子-1(ICAM-1)和白细胞介素-1β(IL-1β)mRNA的表达。结果 与对照组比较,模型组小鼠血脂水平升高,肠道菌群失调,有害菌增加,有益菌减少,血清LPS水平升高,主动脉周围炎症水平升高;与模型组比较,丹蒌片干预可明显降低小鼠总胆固醇(TC)、三酰甘油(TG)及低密度脂蛋白胆固醇(LDL-C)水平(P<0.01),有效减少斑块面积;调节肠道菌群,进而降低血清LPS及主动脉周围炎症因子TNF-α、ICAM-1和IL-1β水平(P<0.01)。结论 丹蒌片通过改善菌群结构,降低菌群失调诱发的炎症反应发挥抗动脉粥样硬化作用。
[Key word]
[Abstract]
Objective To investigate the efficacy and mechanism of Danlou Tablet against atherosclerosis model of ApoE-/- mice fed with high fat diet. Methods C57BL/6J mice were used as controls and ApoE-/- mice were randomly divided into two groups after 24 weeks of high fat feeding, including the model group received saline and the treatment group received Danlou Tablet. Animals were executed after 8 weeks of treatment and serum was collected to measure blood lipids; Plaque formation in the aorta was observed by red O and HE staining; 16 S rRNA sequencing was used to analyze changes in intestinal flora, and GC-MS test for detection fecal SCFAs content, ELISA for the determination of serum LPS, and real time PCR for detection of mRNA expression. Results Compared with the control group, the blood lipid levels were increased; intestinal flora was imbalance with increased harmful bacteria and reduced beneficial bacteria; The level of serum LPS and inflammation around the aorta were increased in the model group. Compared with the model group, the contents of TG, TC, LDL-C and the plaque area of Danlou Tablet group were decreased (P<0.01); Danlou Tablet group can regulate intestinal flora, thus effectively reducing serum LPS and inflammatory factors TNF-α, ICAM-1 and IL-1β levels around the aorta (P<0.01). Conclusion Danlou Tablet exerts an anti-atherosclerosis action with favorable efficacy through restructing the intestinal flora stucture, inhibiting endotoxin releasing and constraining the inflammatory response induced by dysbacteriosis.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金资助项目(81573733);天津市自然科学基金资助项目(18JCYBJC94500);研究生创新基金(ZXYCXLX201804);研究生创新基金(YJSKC-20191003)