Mechanism of Didangtang Against Inflammatory Cascade Triggered by Foam Cell Pyroptosis in High-glucose Environment
10.13422/j.cnki.syfjx.20220604
- VernacularTitle:抵挡汤对高糖环境下泡沫细胞焦亡炎症级联反应的作用机制
- Author:
Qiu-yue REN
1
;
Rong-fei YAO
2
;
Rong-lu YANG
1
;
Ning ZHANG
1
;
Bai CHANG
3
Author Information
1. Wangjing Hospital，China Academy of Chinese Medical Sciences，Beijing 100102，China
2. Minzu University of China，Beijing 100081，China
3. Tianjin Medical University Chu Hsien-I Memorial Hospital， Tianjin Institute of Endocrinology，NHC Key Laboratory of Hormones and Development， Tianjin Institute of Endocrinology，Tianjin 300314，China
- Publication Type:Journal Article
- Keywords:
Didangtang;
high glucose;
pyroptosis;
inflammation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(11):8-15
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Didangtang （DDT） against the inflammatory cascade triggered by foam cell pyroptosis in high-glucose environment. MethodOxidized low density lipoprotein （ox-LDL， 100 mg·L-1） was used to induce pyroptosis of foam cells. The control group （5.5 mmol·L-1 glucose）， foam cell group （100 mg·L-1 ox-LDL）， high-glucose group （33.3 mmol·L-1 glucose）， DDT group （10% DDT-containing serum）， and NOD-like receptor family pyrin domain-containing 3 （NLRP3） inhibitor group （MCC950， 10 nmmol·L-1） were designed. The cell membrane damage was observed by lactate dehydrogenase （LDH） release assay. The expression of cysteinyl aspartate-specific proteinase-1 （Caspase-1） was detected by immunofluorescence method， and expression of key proteins NLRP3， Caspase-1， gastermin D （GSDMD）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in the pyroptosis pathway was determined by Western blot. The release of IL-18 and IL-1β， monocyte chemoattractant protein-1 （MCP-1）， and tumor necrosis factor α （TNF-α） in cell supernatant was measured by enzyme-linked immunosorbent assay （ELISA）. ResultThe expression of NLRP3， Caspase-1， and GSDMD was up-regulated （P<0.01） and the release of IL-1β， IL-18， MCP-1， IL-1α， and TNF-α was increased （P<0.01） in foam cell group compared with those in the control group. The expression of NLRP3， Caspase-1， and GSDMD was higher （P<0.01） and the release of inflammatory factors was more （P<0.01） in the high-glucose group than in the foam cell group. DDT and MCC950 can inhibit expression of NLRP3， Caspase-1， GSDMD and reduce the release of IL-1β， IL-18， MCP-1， IL-1α， and TNF-α. ConclusionDDT can suppress the pyroptosis of foam cells induced by NLRP3/Caspase-1 pathway in high-glucose environment and thereby alleviate the inflammatory cascade.
