摘要
Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related to HBSS by improving inflammatory response,oxidative stress,and blood circulation disorder.This study aimed to elucidate the therapeutic effects and underlying mechanisms of THCQT on vascular endothelial injury induced by HBSS.Methods:LC-MS/MS was used to analyze the chemical components of THCQT.The intervention involved administering saline and appropriate drugs to rats via gavage for 21 days,followed by 24-h repeated tail vein injections of LPS to replicate the HBSS model.Pharmacodynamic assessments included measuring rat body temperature,hemorheology,coagulation function,fever mediators,inflammatory factors,vascular endothelial injury factors,and aortic histopathology to evaluate the preventive effect of THCQT on vascular endothelial injury caused by HBSS.Additionally,proteomics and transcriptomics analyses elucidated THCQT’s impact on mRNA and protein expression levels,further validated by quantitative real-time PCR and Western blot analysis.Results:THCQT was detected to contain 293 chemical components,and some active ingredients with high levels have anti-inflammatory,antioxidant,and inhibiting platelet aggregation properties.Pharmacodynamic results demonstrated that H-THCQT significantly suppressed the elevation of body temperature and downregulated TNF-α,cAMP,and PGE2 expression levels.Additionally,it attenuated the increase in WBV and PV,and prolonged APTT,PT,and TT.It enhanced the expression of NO and PGI2 in plasma,inhibiting ET-1 and TXA2 expression,thus ameliorating aortic pathological injury.Combined transcriptomics and proteomics analyses of the KEGG pathway suggest that the MAPK pathway is crucial in mitigating vascular endothelial injury induced by HBSS through THCQT administration.Furthermore,quantitative real-time PCR and Western blot analyses of the aorta indicated that THCQT inhibits the mRNA and protein phosphorylation levels of p38MAPK,ERK,and JNK in the MAPK signaling pathway of HBSS rats.Conclusion:Our work not only helps explore the common mechanism of THCQT in treating multi-system diseases induced by vascular endothelial injury due to HBSS but also provides a valuable research method for investigating the mechanisms underlying traditional Chinese medicine syndromes.
基金
supported by the National Natural Science Foundation of China(grant No.81973592)
the Shaanxi Provincial Administration of Traditional Chinese Medicine Project(grant No.2021-GJ-JC004).
