Mechanism of Yangmai Tongluo formula in treating homocysteine-induced microcirculation disorders based on the acidic sphingomyelinase/endoplasmic reticulum stress pathway
10.3969/j.issn.1005-4847.2025.08.006
- VernacularTitle:基于酸性鞘磷脂酶-内质网应激通路探究养脉通络方治疗同型半胱氨酸诱导微循环障碍的作用机制
- Author:
Shengtao XIONG
1
;
Weiyan LIAO
;
Qian ZHAO
;
Yue XUAN
;
Zeyu CHEN
;
Donglin LI
;
Xiao WANG
;
Yang CHEN
Author Information
1. 广州中医药大学基础医学院,广州 510006
- Publication Type:Journal Article
- Keywords:
microcirculation disorders;
Yangmai Tongluo formula;
homocysteine;
acid sphingomyelinase;
endoplasmic reticulum stress;
endothelial function
- From:
Acta Laboratorium Animalis Scientia Sinica
2025;33(8):1153-1164
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which Yangmai Tongluo formula improves microcirculation disorders induced by high homocysteine(Hcy)levels via regulation of the acid sphingomyelinase(ASM)and endoplasmic reticulum(ER)stress pathways.Methods Fifty male C57BL/6J mice were divided randomly into a control group,Hcy model group,Yangmai Tongluo formula low-/high dose groups(5.3,10.4 g/kg,respectively),and a folic acid group(0.08 g/kg).Except for the control group,microcirculation disorders were induced in all mice using drinking water containing 1.8 g/L Hcy for 6 weeks.After modeling for 2 weeks,mice were administered the corresponding treatments by gavage for 4 weeks.Serum Hey concentrations and the blood perfusion volume of the lower extremity microvessels were measured.Protein expression levels of zonula occludens ZO-1,ZO-2,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),ASM,glucose-regulated protein 78(GRP78),and C/EBP homologous protein(CHOP)in the cardiac microvascular endothelium were analyzed using immunofluorescence.Results Serum Hcy levels were significantly increased in the Hcy model group compared with the control group(P＜0.05).Yangmai Tongluo formula did not significantly reduce Hey levels compared with the Hey model group,but blood perfusion in the lower extremities was significantly increased(P＜0.01)and expression levels of ZO-1 and ZO-2 in the cardiac microvascular endothelium were restored(P＜0.001)in the Yangmai Tongluo formula high dose group.It also inhibited the expression of ICAM-1,VCAM-1,ASM,GRP78,and CHOP(P＜0.05),with comparable effects to folic acid.Conclusions Yangmai Tongluo formula improves Hcy-induced microcirculation disorders and endothelial dysfunction by inhibiting ASM activity and alleviating ER stress,via a mechanism closely related to the regulation of endothelial inflammation and barrier stability.These result provide experimental evidence to support the use of traditional Chinese medicine to treat microvascular diseases.
