Objective: Myocardial ischemia reperfusion (I/R) damage is a life-threatening vascular emergency after myocardial infarction. Here, we observed the cardioprotective effect of long non-coding RNA (lncRNA) PVT1 knockdown against myocardial I/R damage.

Methods: This study constructed a myocardial I/R-induced mouse model and a hypoxia/reoxygenation (H/R)-treated H9C2 cells. PVT1 expression was examined via RT-qPCR. After silencing PVT1 via shRNA against PVT1, H&E, and Masson staining was performed to observe myocardial I/R damage. Indicators of myocardial injury including cTnI, LDH, BNP, and CK-MB were examined by ELISA. Inflammatory factors (TNF-α, IL-1β, and IL-6), Gasdermin D (GSDMD), and Caspase1 were detected via RT-qPCR, western blot, immunohistochemistry, or immunofluorescence. Furthermore, CCK-8 and flow cytometry were presented for detecting cell viability and apoptosis.

Results: LncRNA PVT1 was markedly up-regulated in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Silencing PVT1 significantly lowered serum levels of cTnI, LDH, BNP, and CK-MB in myocardial I/R mice. H&E and Masson staining showed that silencing PVT1 alleviated myocardial I/R injury. PVT1 knockdown significantly lowered the production and release of inflammatory factors as well as inhibited the expression of GSDMD-N and Caspase1 in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Moreover, silencing PVT1 facilitated cell viability and induced apoptosis of H/R-treated H9C2 cells.

Conclusion: Our findings demonstrated that silencing PVT1 could alleviate myocardial I/R damage through suppressing GSDMD-mediated pyroptosis in vivo and in vitro. Thus, PVT1 knockdown may offer an alternative therapeutic strategy against myocardial I/R damage.

客观的：心肌缺血再灌注 (I/R) 损伤是心肌梗死后危及生命的血管紧急情况。在这里，我们观察了长链非编码 RNA (lncRNA) PVT1 敲低对心肌 I/R 损伤的心脏保护作用。

方法：本研究构建了心肌 I/R 诱导的小鼠模型和缺氧/复氧 (H/R) 处理的 H9C2 细胞。通过 RT-qPCR 检查 PVT1 表达。在通过针对 PVT1 的 shRNA 沉默 PVT1 后，进行 H&E 和 Masson 染色以观察心肌 I/R 损伤。ELISA检测cTnI、LDH、BNP、CK-MB等心肌损伤指标。通过 RT-qPCR、蛋白质印迹、免疫组织化学或免疫荧光检测炎症因子（TNF-α、IL-1β 和 IL-6）、Gasdermin D (GSDMD) 和 Caspase1。此外，CCK-8 和流式细胞术用于检测细胞活力和细胞凋亡。

结果：LncRNA PVT1 在心肌 I/R 组织标本以及 H/R 诱导的 H9C2 细胞中显着上调。沉默 PVT1 可显着降低心肌 I/R 小鼠的 cTnI、LDH、BNP 和 CK-MB 的血清水平。H&E 和 Masson 染色显示沉默 PVT1 减轻了心肌 I/R 损伤。PVT1 敲低显着降低炎症因子的产生和释放，并抑制心肌 I/R 组织标本以及 H/R 诱导的 H9C2 细胞中 GSDMD-N 和 Caspase1 的表达。此外，沉默 PVT1 促进细胞活力并诱导 H/R 处理的 H9C2 细胞凋亡。

结论： 我们的研究结果表明，沉默 PVT1 可以通过抑制 GSDMD 介导的细胞焦亡减轻心肌 I/R 损伤 体内 和 体外. 因此，PVT1 敲低可能提供另一种治疗心肌 I/R 损伤的策略。