基于代谢组学探讨扶正祛瘀通下法治疗脓毒症大鼠心肌损伤作用机制  

Metabonomical and mechanistic study of Strengthening Vital Qi and Resolving Blood Stasis and Purging Treatment with Shenfu Taohong Chengqi decoction for myocardial injury in a rat model of sepsis

作　　者：潘振亚 赵娜 马晨瑜 祝韵薇 邓旻[1] PAN Zhen-ya;ZHAO Na;MA Chen-yu;ZHU Yun-wei;DENG Min(Department of emergency,Hangzhou Red Cross Hospital,Hangzhou 310003,China;The Second Clinical Medical College,Zhejiang Chinese Medical University,Hangzhou 310053,China;Department of Child Healthcare,The Hangzhou Jianggan TCM Hospital,Hangzhou 310016,China)

机构地区：[1]杭州市红十字会医院急诊医学科,杭州310003 [2]浙江中医药大学第二临床医学院,杭州310053 [3]杭州市江干区中医医院儿童保健科,杭州310016

出　　处：《浙江中西医结合杂志》2021年第9期804-809,共6页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：杭州市科技局社会发展科研自主申报项目(医疗卫生)(No.20180533B75)。

摘　　要：目的基于代谢组学探讨扶正祛瘀通下法(参附桃红承气汤)治疗脓毒症大鼠心肌损伤的作用机制。方法将30只Wistar大鼠按照随机数字表法分为模型组、实验组和空白对照组,每组10只。采用腹腔注射脂多糖法制备脓毒症大鼠模型。实验组大鼠给予参附桃红承气汤灌胃,模型组给予等量生理盐水灌胃。造模成功后12h观察各组大鼠心功能,随后处死大鼠,取心脏组织并于电镜下观察,同时基于液相色谱-质谱联用技术对大鼠肠道代谢产物进行模式识别与分析,鉴定差异代谢物并分析其富集的代谢通路。结果实验组大鼠左心室射血分数较模型组大鼠显著升高[(72.15±8.09)%比(56.36±5.58)%,P<0.05],但低于空白对照组[(72.15±8.09)%比(82.42±4.12)%,P<0.05];空白对照组大鼠心肌细胞线粒体结构完整无损伤,实验组出现少量线粒体损伤及脊线断裂,而模型组有大量线粒体肿胀、坏死,并且出现脊断裂及空泡化;代谢组学结果方面,在扶正祛瘀通下药物干预前后大鼠肠道代谢谱明显分离,最终筛选出山奈酚、异亮氨酸、柚皮素、芦荟苷、芹菜素、7-脱氢胆固醇、N-甲基酪胺、灵芝酸、5-羟基吲哚乙酸等9种差异代谢物,主要富集于黄酮类合成、氨基酸(异亮氨酸、酪氨酸、色氨酸)代谢、苯丙酸代谢、类固醇激素生物合成等6条代谢通路。结论扶正祛瘀通下法可改善脓毒症大鼠心肌损伤,其机制可能与黄酮类的合成、氨基酸代谢、苯丙酸代谢、类固醇激素生物合成密切相关。Objective To explore the mechanism of Strengthening Vital Qi and Resolving Blood Stasis and Purging Treatment with Shenfu Taohong Chengqi decoction for myocardial injury in a rat model of sepsis.Methods A total of 30 Wistar rats were randomly divided into model,treatment,and control groups(n=10 per group).Rats in the model and treatment groups were induced sepsis using intraperitoneal injection of lipopolysaccharide(LPS).The rats in the treatment group were given Shenfu Taohong Chengqi decoction by oral gavage and the rats in the model group were given an equal amount of normal saline orally.The cardiac functions and myocardial electron microscopy of rats in each group were observed 12h thereafter.The intestinal metabolites were then assessed using the liquid chromatography-mass spectrometry(LC-MS).Results The left ventricular ejection fraction(LVEF)of treatment rats was significantly improved compared to that of the model rats(72.15±8.09 vs.56.36±5.58%;P<0.05),although it was lower than that of the control rats(72.15±8.09 vs.82.42±4.12%,P<0.05).The mitochondrial structure in the myocardial cells was intact without any changes in the control rats,whereas the treatment rats only showed some level of mitochondrial injury and ridge rupture vs.the model group that showed a large number of swelling and necrotic mitochondria with ridge rupture and vacuolation.Furthermore,the intestinal metabolic spectrum clearly separated after the drug intervention for the body vital qi strengthening and blood stasis removal,i.e.,there were nine kinds of different metabolites altered,including kaempferol,isoleucine,aloin,naringenin,apigenin,7-dehydrocholesterol,N-methyltyramine,ganodenic acid,and 5-hydroxyindoleacetic acid,all of which were mainly involved in the metabolic pathways of synthesis of flavonols,metabolism of amino acid,and phenylpropionic acid(L-isoleucine,tyrosine,and tryptophan),biosynthesis of steroid hormone were screened.Conclusion The Strengthe-ning Vital Qi and Resolving Blood Stasis and Purging Treatment could

关 键 词：大鼠 代谢组学 扶正祛瘀通下法 脓毒症 心肌损伤 

分 类 号：R285.5[医药卫生—中药学]