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肠源性氧化三甲胺对缺血性心力衰竭大鼠预后的影响OACSTPCD

Effect of intestinal-derived trimethylamine oxide levels on prognosis of ischemic heart fail-ure rats

中文摘要英文摘要

目的 评估氧化三甲胺(TMAO)对缺血性心力衰竭大鼠预后的影响.方法 SD大鼠随机分为正常对照组、假手术组、模型(HF)组、干预(HF-DMB)组,其中HF组与HF-DMB组大鼠行结扎法模拟心肌梗死,分别于术后 4 周(4 W)、8 周(8 W)、12 周(12 W)评估心脏功能,检测血清TMAO、脑钠肽(BNP)、C反应蛋白(CRP)、内毒素(LPS)、白介素-6(IL-6)等水平,心肌组织进行HE染色及Masson染色,取粪便组织进行 16S rDNA高通量测序分析.结果 与正常对照组比较,HF组LVEF随时间明显下降,且在 8W时下降尤为明显(27.68%±6.41%),HF组各时间点循环TMAO[(9534.02±202.75)nmol/L、(12713.06±243.66)nmol/L、(4970.95±168.15)nmol/L)]、BNP[(37.26±3.41)ng/L、(59.17±3.80)ng/L、(58.83±4.41)ng/L]、CRP[(179.30±13.85)μg/L、(186.40±13.47)μg/L、(187.21±11.35)μg/L]、LPS[(92.45±8.83)ng/L、(90.65±7.5)ng/L、(95.20±4.68)ng/L]、IL-6[(97.57±3.48)pg/ml、(102.60±4.96)pg/ml、(107.70±4.70)pg/ml]等指标浓度较正常对照组明显升高且差异具有统计学意义(P<0.05),HF-DMB组LVEF在各时间点有所回升,且循环中各指标均较HF组有不同程度下降(P<0.05),且TMAO水平变化与其他指标改变一致;心肌病理染色提示HF-DMB组较HF组心肌细胞存活更多且纤维化程度有所减轻;测序分析中,与HF组比较,HF-DMB组菌落丰度增加,HF-8W组厚壁菌门/拟杆菌门比值下降,而HF-DMB-8W组变化与HF-8W组相反.结论 缺血性心力衰竭大鼠循环TMAO变化与传统心力衰竭评价指标变化一致,特异性抑制循环TMAO能够改善心力衰竭多项指标,在心力衰竭的治疗和预后评估中具有一定的临床价值.

Objective To evaluate the effect of trimethylamine oxide(TMAO)on the prognosis of ischemic heart failure rats.Methods SD rats were randomly divided into normal control group,sham group,model group(HF)and intervention group(HF-DMB).Rats in HF and HF-DMB groups underwent myocardial infarction simulation via ligation,and cardiac function was assessed at 4 weeks(4 W),8 weeks(8 W)and 12 weeks(12 W)after surgery,respectively.The levels of Serum TMAO,BNP,CRP,LPS and IL-6 were detected,along with histological examination of myocardial tissue using HE and Masson staining.Fecal samples were al-so collected for 16S rDNA high-throughput sequencing analysis.Results Compared with Control group,HF group exhibited a signifi-cant decline in(LVEF)over time,the difference was most pronounced in the eighth week(27.68±6.41)%,also with a notable in-crease in circulating TMAO[(9534.02±202.75)nmol/L,(12713.06±243.66)nmol/L,(4970.95±168.15)nmol/L],BNP[(37.26±3.41)ng/L,(59.17±3.80)ng/L,(58.83±4.41)ng/L],CRP[(179.30±13.85)μg/L,(186.40±13.47)μg/L,(187.21±11.35)μg/L],LPS[(92.45±8.83)ng/L,(90.65±7.5)ng/L,(95.20±4.68)ng/L],IL-6[(97.57±3.48)pg/ml,(102.60±4.96)pg/ml,(107.70±4.70)pg/ml],levels compared with the control group(P<0.05).Myocardial pathological staining showed that more myocardial cells survived and the degree of fibrosis was reduced in HF-DMB group than in HF group.Sequencing analysis re-vealed increased microbial richness in the HF-DMB group compared with the HF group with increased Firmicutes and decreased Bacteroidetes at 8 weeks,resulting in a lowered Firmicutes/Bacteroidetes ratio.However,these changes were reversed in the HF-DMB-8W group.Conclusions Changes of circulating TMAO in ischemic heart failure rats are consistent with traditional heart failure evaluation markers.Specific in-hibition of circulating TMAO can improve various indexes of heart failure,indicating its potential clinical value in heart failure treatment and prognostic assessment.

张芯;石蕊;倪健美;刘小伟;郭琼;王涛;王晓静;陈少伯

300162,武警特色医学中心高原高寒环境及心血管病防治研究所/天津市心血管重塑与靶器官损伤重点实验室300199,天津市中西医结合南开医院

基础医学

氧化三甲胺心力衰竭3,3-二甲基-1-丁醇肠道菌群

trimethylamine oxideheart failure3,3-dimethyl-1-butanolgut microbiota

《武警医学》 2024 (006)

474-479 / 6

天津市应用基础研究项目(21JCQNJC01230);中心级创新团队课题(KYCXTD0502)

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