[關(guān)鍵詞]
[摘要]
目的 探討注射用益氣復(fù)脈(凍干)(YQFM)對慢性心力衰竭(CHF)大鼠的腸道菌群的影響。方法 采用腹主動脈縮窄法制備CHF大鼠模型,選取造模成功的大鼠隨機(jī)分為3組:模型組和YQFM低、高劑量(464.3、928.6 mg·kg-1,464.3 mg·kg-1為臨床等效劑量)組;假手術(shù)組大鼠進(jìn)行切口和縫合,但不進(jìn)行結(jié)扎縮窄。每天尾iv給藥1次,連續(xù)給藥14 d,假手術(shù)組和模型組尾iv給予0.9%氯化鈉注射液。給藥前后采用超聲診斷儀檢測大鼠心功能;給藥14 d后取血,ELISA法檢測大鼠血清心鈉肽(ANP)、腦鈉肽(BNP)、肌酸激酶同工酶(CK-MB)、內(nèi)皮素(ET)、丙二醛(MDA)水平;取出盲腸位置糞便,進(jìn)行高通量16S rRNA測序分析。結(jié)果 與模型組比較,YQFM組大鼠的左室短軸縮短率(LVFS)和左室射血分?jǐn)?shù)(LVEF)均顯著升高(P<0.01、0.001),ANP、BNP、CK-MB、ET、MDA水平均顯著下降(P<0.001)。Venn圖結(jié)果顯示,CHF模型可以使大鼠腸道菌群數(shù)量下降;α多樣性分析結(jié)果顯示,與模型組比較,YQFM組的Chao1、Shannon、Simpson指數(shù)均顯著上升(P<0.05、0.01);在非度量多維尺度(NMDS)和主坐標(biāo)分析(PCoA)中,YQFM組與假手術(shù)組的差異比模型組與假手術(shù)組的差異?。辉陂T水平下,與模型組相比,YQFM組的厚壁菌門相對豐度升高,高劑量組差異顯著(P<0.01),YQFM組的擬桿菌門相對豐度有降低趨勢,YQFM低、高劑量組的厚壁菌門/擬桿菌門(F/B)呈升高趨勢。在豐度等級曲線中,模型組與假手術(shù)組的差距大,YQFM組更接近假手術(shù)組,腸道菌群的均勻度明顯回升。結(jié)論 YQFM改善CHF大鼠的心功能,緩解炎癥反應(yīng),改善腸道菌群紊亂。
[Key word]
[Abstract]
Objective To investigate the effect of Yiqi Fumai Lyophilized Injection on intestinal microbiota in rats with chronic heart failure (CHF). Method The rat model of CHF was established by constriction of abdominal aorta. The rats that successfully established the model were randomly divided into three groups: model group and YQFM low and high dose (464.3, 928.6 mg·kg-1, 464.3 mg·kg-1 as clinical equivalent dose) groups. The rats in the sham-operated group group were cut and sutured, but not ligated or narrowed. The drug was administered iv once a day for 14 consecutive days, and 0.9% sodium chloride injection was administered intravenously in the sham-operated group and the model group. Ultrasound diagnostic equipment was used to detect the cardiac function of rats before and after administration; Blood samples were taken 14 days after administration, and the serum levels of cardiac natriuretic peptide (ANP), brain natriuretic peptide (BNP), creatine kinase isozyme (CK-MB), endothelin (ET), and malondialdehyde (MDA) were detected by ELISA. Remove feces from the cecal site and perform high-throughput 16Sr RNA sequencing analysis. Result Compared with the model group, the left ventricular short axis shortening rate (LVFS) and left ventricular ejection fraction (LVEF) of YQFM group rats were significantly increased (P<0.01, 0.001), and the levels of ANP, BNP, CK-MB, ET, MDA were significantly decreased (P<0.001). Venn diagram results showed that CHF model could reduce the number of gut microbiota in rats. The diversity analysis results showed that compared with the model group, the Chao1, Shannon, and Simpson indices of the YQFM group significantly increased (P<0.05, 0.01). In non metric multidimensional scale (NMDS) and principal coordinate analysis (PCoA), the difference between YQFM group and sham-operated group was smaller than that between model group and sham-operated group. At the phyla level, compared with the model group, the relative abundance of Bacillota in the YQFM group increased, with a significant difference in the high-dose group (P<0.01). The relative abundance of Bacteroidota in the YQFM group decreased, and the relative abundance of Bacillota/Bacteroidota (F/B) in the low-dose and high-dose YQFM groups increased. In the abundance grade curve, there was a big gap between the model group and the sham-operated group. The YQFM group was closer to the sham-operated group, and the evenness of gut microbiota obviously rised. Conclusion YQFM can improve the heart function of CHF rats, alleviate inflammatory reaction, and improve gut microbiota disorder.
[中圖分類號]
R285.5
[基金項目]