TLR4/NF-kappaB p65 signaling pathway mediates protective effect of triptolide on endothelium in rats with endotoxemia.
10.19540/j.cnki.cjcmm.20190701.402
- Author:
Jia-Qi ZONG
1
;
Shuo-Yang WANG
2
;
Ping SU
1
;
Bei-Bei SUN
1
;
Ma-di GUO
2
;
Guang-Hua DIAO
2
;
Jing WANG
1
;
Hai-Hua WANG
1
Author Information
1. Department of Physiology,Wannan Medical College Wuhu 241002,China.
2. Department of Clinical Medicine,Wannan Medical College Wuhu 241002,China.
- Publication Type:Journal Article
- Keywords:
TLR4/NF-kappaB p65 signaling pathway;
endotoxemia;
lipopolysaccharide;
rats;
triptolide
- MeSH:
Animals;
Diterpenes/pharmacology*;
Endothelium;
Endotoxemia;
Epoxy Compounds/pharmacology*;
Lipopolysaccharides;
Male;
NF-kappa B;
Phenanthrenes/pharmacology*;
Protective Agents/pharmacology*;
Random Allocation;
Rats;
Rats, Sprague-Dawley;
Signal Transduction;
Toll-Like Receptor 4/metabolism*;
Tumor Necrosis Factor-alpha
- From:
China Journal of Chinese Materia Medica
2019;44(22):4912-4917
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this paper was to observe the effect of triptolide( TP) on cardiovascular function and its possible mechanism by intraperitoneal injection of bacterial lipopolysaccharide in rats with endotoxemia. Sixty male Sprague-Dawley rats were randomly divided intonormal group( NC group),endotoxemia model group( LPS group),TP low concentration intervention group( LPS + TP-L group,25 μg·kg~(-1)),TP middle concentration intervention group( LPS+TP-M group,50 μg·kg~(-1)),TP high concentration intervention group( LPS+TP-H group,100 μg·kg~(-1)) and polymyxin B group( LPS+PMX-B group,0. 2 mg·kg~(-1)). 10 mg·kg~(-1) LPS was injected intraperitoneally for 6 h to replicate the endotoxemia rat model. The rats in TP intervention groups were pre-treated 15 min before intraperitoneal injection of LPS. Rats in each group underwent total arterial intubation to measure hemodynamic parameters: heart rate( HR),left ventricular diastolic pressure( LVDP),the maximum rate of the increase/decrease of left ventricular pressure( ±dp/dtmax). The levels of BNP,CK-MB and c Tn-Ⅰ in serum and levels of TNF-α and IL-6 in plasma were detected by ELISA. The contents of p65 protein in myocardium and contents of p65,TLR4,i NOS and e NOS protein in thoracic aorta were detected by Western blot. As compared with NC group,the hemodynamic indexes in LPS group were significantly decreased; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly increased. As compared with LPS group,the hemodynamic indexes were significantly improved in LPS+TP-M group,LPS+TP-H group and LPS+PMX-B group; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly decreased in each treatment group. Triptolide has a protective effect on cardiovascular damage in a dose-dependent manner in endotoxemia rats,probably through TLR4/NF-κB p65 signaling pathway to improve endothelial function.
