Naoluo Xintong Decoction activates caspase-1/Gasdermin D pathway to promote angiogenesis of rat brain microvascular endothelial cells after oxygen glucose deprivation/reperfusion injury.
10.12122/j.issn.1673-4254.2023.07.05
- Author:
Peipei LI
1
;
Yinqi HU
1
;
Jia LIU
1
;
Lina WANG
1
;
Yuanjie WU
2
;
Jianpeng HU
1
Author Information
1. Ministry of Education Key Laboratory of Xin'an Medicine, Anhui University of Chinese Medicine, Hefei 230038, China.
2. School of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230012, China.
- Publication Type:Journal Article
- Keywords:
Naoluo Xintong Decoction;
angiogenesis;
brain microvascular endothelial cells;
oxygen-glucose deprivation/reperfusion;
pyroptosis;
vascular endothelial growth factor
- MeSH:
Animals;
Rats;
Endothelial Cells;
Caspase 1;
Gasdermins;
Interleukin-18;
NLR Family, Pyrin Domain-Containing 3 Protein;
Vascular Endothelial Growth Factor A;
Reperfusion Injury;
Brain;
Angiogenic Proteins;
Glucose
- From:
Journal of Southern Medical University
2023;43(7):1093-1101
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effects of Naoluo Xintong Decoction (NLXTD) on pyroptosis and angiogenesis of brain microvascular endothelial cells (BMECs) and explore the possible mechanisms in rats with oxygen-glucose deprivation/ reperfusion (OGD/R).
METHODS:Rat BMECs with or without caspase-1 siRNA transfection were cultured in the presence of 10% medicated serum from NLXTD-treated rats (or blank serum) and exposed to OGD/R. CCK-8 assay, Transwell chamber assay, and tube formation assay were used to assess proliferation, migration, and tube-forming abilities of the cells. The activity of lactate dehydrogenase (LDH) in the culture supernatant was determined using a commercial assay kit, and the levels of inflammatory factors IL-1β and IL-18 were detected with ELISA. The cellular expressions of pro-caspase-1, caspase-1, NLRP3, Gasdermin D, and angiogenesis-related proteins VEGF and VEGFR2 were detected using Western blotting.
RESULTS:The BMECs showed obvious injuries after OGD/R exposure. Compared with the blank serum, the medicated serum significantly improved the cell viability, migration ability, and lumen-forming ability (P < 0.01) and lowered the levels of IL-1β and IL-18 and the LDH release (P < 0.01) of the cells with OGD/R exposure. Western blotting showed that in the BMECs exposed to OGD/R, the medicated serum strongly upregulated the expression of VEGF and VEGFR2 proteins (P < 0.01) and reduced the protein expressions of pro-caspase-1, caspase-1, NLRP3, and Gasdermin D (P < 0.01), and transfection of the cells with caspase-1 siRNA further promoted the expressions of VEGFR2 protein in the cells (P < 0.01).
CONCLUSION:NLXTD can improve the proliferation, migration, and tube- forming ability and promote angiogenesis of BMECs with OGD/R injury probably by inhibiting the caspase-1/Gasdermin D pathway in pyroptosis, alleviating cell injury, and upregulating the expressions of VEGF and VEGFR2.
