Objective: To explore whether SPH3127, a novel renin inhibitor, can protect human umbilical vein fusion cell line EA.hy926 injury induced by angiotensin Ⅱ (AngⅡ) by inhibiting pyroptosis. Methods: The EA.hy926 in logarithmic growth phase was intervened with AngⅡ to construct the hypertension model at the cellular level in vitro. The control group, model group, SPH3127 group and pyroptosis inhibitor MCC950 group were set up respectively. The cell viability was detected by CCK8 method and the cell survival rate was calculated. Cell scratches were used to determine migration; nitrate reductase method was used to detect the content of nitric oxide (NO) in medium of each group. The contents of endothelin-1 (ET-1), interleukin-1β (IL-1β) and IL-18 in medium of each group were detected by ELISA. Western blot was used to detect the protein expression of pyroptosis-related substances NLR family pyrin domain containing 3 (NLRP3), cysteine-requiring aspartate protease-1 (Caspase-1) and N-terminal of pyroptosis protein Gasdermin D (GSDMD-N) in EA.hy926 of each group. Results: Compared with the control group, the survival rate, healing rate and NO content of EA.hy926 cells in the model group were decreased (P＜0.05). The contents of ET-1, IL-1β, IL-18 and the expression levels of NLRP3, Caspase-1 and GSDMD-N protein were increased (P＜0.05). Compared with the model group, the cell survival rate, healing rate and NO content in the SPH3127 group and the MCC950 group were increased (P＜0.05). The contents of ET-1, IL-1β, IL-18 and the expression levels of NLRP3, Caspase-1 and GSDMD-N were decreased (P＜0.05). Compared with MCC950 group, the cell survival rate, healing rate, NO, IL-1β, IL-18 content and NLRP3, Caspase-1, GSDMD-N protein expression levels in SPH3127 group were increased (P＜0.05). ET-1 content decreased (P＜0.05). Conclusion: SPH3127 can effectively improve the survival rate of EA.hy926 cells, reduce the inflammatory response by inhibiting the pyroptosis pathway, and play a protective role in EA.hy926 injury induced by AngⅡ.
ZHU Yaquan
,
LI Yu
,
MA Wen
,
ZHANG Xin
. Effect of SPH3127 on AngⅡ-induced EA.hy926 injury based on pyroptosis pathway[J]. Journal of Baotou Medical College, 2025
, 41(8)
: 43
-47
.
DOI: 10.16833/j.cnki.jbmc.2025.08.008
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