冠心宁片通过调节肠道微生态改善大鼠早期心衰

Guanxinning Tablet Improves Early Heart Failure in Rats by Regulating Intestinal Microflora

目的观察冠心宁片(Guanxinning tablets,GXN)对早期心衰模型大鼠的影响,并从肠道菌群角度探讨GXN对心衰大鼠的保护机制。方法取6只SD大鼠行假手术,另取80只SD大鼠行主动脉弓狭窄术,建立心力衰竭大鼠模型,将存活的大鼠分为4组,即模型对照组、阳性对照组(卡托普利片12.5 mg·kg^(-1))和GXN高、低剂量组(1200、600 mg·kg^(-1)),连续给药8周。每隔4周进行心动超声检查,检测血清NT-proBNP、hs-CRP、IL-6和TNF-α浓度及SOD与MDA水平;取大鼠结肠内容物,基于16S肠道微生物组高通量测序技术和生物信息学分析手段,观察GXN对肠道菌群结构和功能的影响。结果与模型对照组相比,给予不同剂量的GXN后大鼠存活率均有提高,心室壁厚度均有不同程度的下降,大鼠心脏质量及脏器系数均有改善。GXN还能降低炎症因子水平,抑制大鼠NT-proBNP水平升高,提高血清SOD活性。另外,GXN干预后能显著提高心衰模型大鼠的肠道菌群多样性,可能的作用菌属靶点为Akkermansia属、Phascolarctobacterium属和Oxalobacter属。GXN对心衰大鼠肠道菌群功能的影响可能集中在非同源末端连接、流感A、类胡萝卜素合成、吲哚生物碱、贝他林生物合成、肾素-紧张素系统等生物途径。结论GXN对早期心衰大鼠的保护作用可能与调节肠道菌群途径有关。

OBJECTIVE To investigate the effect of Guanxinning tablets(GXN)on early heart failure model rats,and to explore the protective mechanism of GXN on heart failure rats from the perspective of intestinal flora.METHODS Six rats who underwent sham operation were set as sham operation group.Took 80 SD rats to undergo aortic arch stenosis and established a heart failure rat model.The surviving rats were divided into 4 groups,namely the model control group,the positive control group(captopril tablets 12.5 mg·kg^(-1)),high-dose and low-dose of GXN group(600,1200 mg·kg^(-1)).The 4 groups were administered continuously for 8 weeks.Cardiac ultrasonography was performed every 4 week.Serum NT-proBNP,hs-CRP,IL-6,TNF-α,SOD and MDA levels were measured.The effects of GXN on the structure and function of intestinal flora were observed based on the high-throughput sequencing technology and bioinformatics analysis of 16S gut microbiome.RESULTS Compared to the model control group,after giving different doses of GXN,the survival rate of rats increased,and the thickness of the ventricular wall decreased to varying degrees.The weight of the heart and coefficient of the heart were all reduced.GXN could also reduce the level of inflammatory factors,inhibit the level increase of NT-proBNP in rats,and increase the activity of serum SOD.In addition,GXN intervention could significantly improve the intestinal flora diversity of rats with heart failure,the possible target genera of GXN were Akkermansia genera,Phascolarctobacterium genera and Oxalobacter genera.The effect of GXN on intestinal function in rats with heart failure might be concentrated in non-homologous end-joining,influenza A,carotenoid synthesis,indole alkaloids biosynthesis,betalain biosynthesis,renin-angiotensin system and other biological pathways.CONCLUSION The protective effect of GXN on early heart failure rats may be related to the regulation of intestinal flora pathway.