Dachaihu decoction protects intestinal mucosal barrier in severe heat stroke rats by inhibiting Toll-like receptor 4/nuclear factor-κB signaling pathway
10.3969/j.issn.1008-9691.2023.05.015
- VernacularTitle:大柴胡汤抑制TLR4/NF-κB信号通路保护重症中暑大鼠胃肠道黏膜屏障机制的研究
- Author:
Dongjie CHEN
1
;
Yonglian HUANG
;
Xiaohong PENG
;
Yaxiu HUANG
;
Fagen HUANG
;
Aiting ZHANG
;
Ping WANG
Author Information
1. 北京中医药大学深圳医院(龙岗)重症医学科,广东深圳 518000
- Keywords:
Dachaihu decoction;
Severe heat stroke;
Inflammatory response;
Intestinal mucosal barrier
- From:
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
2023;30(5):592-596
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of Dachaihu decoction on the Toll-like receptor 4/nuclear factor-κB(TLR4/NF-κB)signaling pathway and gastrointestinal mucosal barrier in rats with severe heat stroke.Methods Sixty SPF grade Sprague-Dawley(SD)male rats were divided into normal control group,model group,Dachaihu decoction standard dose group and Dachaihu decoction high dose group of 15 rats in each group.The heat stroke model was replicated in the rats at temperature(40.5±0.5)℃and humidity(65.0±2.0)%;the normal control group was not treated.From 6 hours after mold making,drug intervention was carried out in the Dachaihu decoction high dose group and the Dachaihu decoction standard dose group of 3.38 g·kg-1·d-1 and 1.69 g·kg-1·d-1,every 8 hours for 2 days.Equal amounts of normal saline were administered to the normal control group and model group.At 6,24 and 48 hours after the molding,5 mL abdominal main artery blood from 5 rats were randomly collected from each group,and the blood was obtained by enzyme-linked immunosorbent assay(ELISA)to determine the levels of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),D-lactic acid,intestinal fatty acid-binding protein(I-FABP).At the same time,the ileum tissue was retained,and the protein expression of TLR4 and NF-κB in intestinal tissue was determined by Western blotting.Some of the ileal tissue was obtained for hematoxylin-eosin(HE)staining,and the intestinal histopathological changes were observed under light microscopy.Results The normal control group of rats had no significant change,and the other three groups showed heatstroke symptoms after mold making.The overall mortality in drug group were significantly lower than that in the model group[3.3%(1/30)vs.20.0%(3/15),P＜0.05].Compared with the normal control group,the serum IL-1,TNF-α,I-FABP,D-lactic acid and the protein expression levels of TLR4 and NF-κB in the model group,Dachaihu decoction standard dose group and Dachaihu decoction high dose group all increased.Compared with the model group,at 24 hours and 48 hours after molding in the Dachaihu decoction standard dose group and Dachaihu decoction high dose group,the serum IL-1,TNF-α,I-FABP,D-lactic acid and the protein expression levels of TLR4 and NF-κB significant decreased[24 hours:TNF-α(ng/L):69.20±4.32,59.37±4.31 vs.76.99±5.02,IL-1(ng/L):132.68±4.93,112.59±9.64 vs.146.75±10.12,I-FABP(mmol/L):504.35±22.23,453.37±32.38 vs.542.58±13.83,D-lactic acid(mmol/L):114.55±8.52,90.57±3.09 vs.127.87±8.37,protein expression of TLR4(A value):1.50±0.08,1.23±0.01 vs.1.86±0.08,protein expression of NF-κB(A value):1.61±0.05,1.21±0.05 vs.1.97±0.08;48 hours:TNF-α(ng/L):58.46±5.13,38.98±5.53 vs.90.21±3.02,IL-1(ng/L):119.12±4.57,84.12±5.08 vs.170.20±6.21,I-FABP(mmol/L):436.04±27.63,321.85±22.03 vs.618.79±12.31,D-lactic acid(mmol/L):87.35±6.84,70.38±4.33 vs.154.14±10.83,protein expression of TLR4(A value):1.19±0.05,1.10±0.13 vs.2.09±0.06,protein expression of NF-κB(A value):1.15±0.09,0.97±0.08 vs.2.20±0.02,all P＜0.05].The expression levels of TNF-α,I-FABP,TLR4 and NF-κB protein in Dachaihu decoction high dose group decreased significantly at 24 hours and 48 hours compared with the standard dose group,however,IL-1 and D-lactic acid decreased significantly at 48 hours after molding(all P＜0.05).The pathology observation showed that,compared with the model group,the intestinal mucosa villus,the lamina propria drop and haemorrhage was decreased in the Dachaihu decoction standard dose group and Dachaihu decoction high dose group.Telangiectasia was reduced and no ulcer formation was observed.Conclusion Dachaihu decoction can inhibit TLR4/NF-κB signaling pathway,reduce intestinal inflammatory response,thus reduce gastrointestinal damage,and protect the gastrointestinal mucosal barrier in rats with severe heatstroke.
