Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H₂O₂, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.

缺血再灌注（I / R）损伤是一个器官受到短暂减少的血液供应时触发的多因素过程。结果是由于再灌注后产生活性氧而导致一系列病理并发症和器官损伤。本研究旨在评估活化的钙敏感受体（CaR）-胱硫醚γ-裂解酶（CSE）/硫化氢（H2S）途径在I / R损伤中的作用。首先，构建了具有CSE基因敲除的I / R大鼠模型。经胸超声心动图，TTC和HE染色确定I / R损伤后大鼠的心功能，然后进行TUNEL染色观察细胞凋亡。此外，为了更好地阐明CaR-CSE / H2S在体外如何影响I / R用氯化g（GdCl3，CaR激动剂），H ₂ O ₂进行人冠状动脉内皮细胞（HCAEC）的培养，针对CSE的siRNA（siCSE）或W7（一种CaM抑制剂）。随后检测到CSE和CaM之间的相互作用。细胞凋亡后，分析血浆氧化应激指数，H2S和CSE以及凋亡相关蛋白。我们发现，H2S升高导致I / R损伤大鼠心脏功能改善，而CSE抑制作用降低了心脏功能。此外，CSE基因敲除的I / R大鼠的氧化应激损伤加剧，而主动脉组织中H2S和CSE表达的增加则减轻了氧化应激损伤。而且，发现增加的H 2 S和CSE水平抑制了I / R损伤后主动脉组织中的细胞凋亡能力，从而减轻了氧化应激损伤，并伴随着凋亡相关蛋白的表达被抑制。在氧化应激处理后的HCAEC中，观察到siCSE和CaM抑制剂可逆转CaR激动剂的保护作用。免疫共沉淀测定揭示了CSE和CaM之间的相互作用。综上所述，所有上述数据提供了证据，表明CaR-CSE / H2S途径的激活可能在心脏I / R损伤中产生有效的保护作用。