【目的】 基于调控硫氧还蛋白相互作用蛋白（TXNIP）-Nod样受体蛋白3（NLRP3）通路探讨黄芪甲苷对缺氧复氧诱导的 心肌细胞损伤的修复作用。【方法】 将心肌细胞H9c2分为空白组，缺氧复氧组，黄芪甲苷低、高剂量组，黄芪甲苷高剂量 + pcDNA-NC组和黄芪甲苷高剂量+pcDNA-TXNIP组。分组处理后，细胞计数试剂盒8（CCK-8）法检测H9c2细胞增殖情况，流 式细胞术检测H9c2细胞凋亡情况，可溶性噻唑盐8（WST-8）法检测H9c2细胞中乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD） 活性，2’，7’-二氯荧光素二乙酸酯（DCFDA）荧光探针法检测 H9c2细胞中活性氧（ROS）生成量，酶联免疫吸附分析（ELISA） 测定 H9c2细胞中白细胞介素 6（IL-6）和肿瘤坏死因子 α（TNF-α）水平，Western Blot法测定细胞 TXNIP和 NLRP3蛋白表达水 平。【结果】 与空白组比较，缺氧复氧组中H9c2细胞存活率和SOD活性均显著降低（P＜0.05），细胞凋亡率，LDH水平，ROS 生成量，IL-6、TNF-α水平及TXNIP、NLRP3蛋白表达量均显著增加（P＜0.05）；与缺氧复氧组比较，黄芪甲苷低、高剂量 组中细胞存活率和 SOD 活性显著升高（P＜0.05），细胞凋亡率，LDH 水平，ROS 生成量，IL-6、TNF-α 水平及 TXNIP、 NLRP3蛋白表达量均显著降低（P＜0.05）；与黄芪甲苷高剂量+pcDNA-NC组比较，黄芪甲苷高剂量+pcDNA-TXNIP组中细胞 存活率和SOD活性显著降低（P＜0.05），细胞凋亡率，LDH水平，ROS生成量，IL-6、TNF-α水平及TXNIP、NLRP3蛋白表 达量均显著增加（P＜0.05）。【结论】 黄芪甲苷可能通过下调TXNIP-NLRP3通路中关键蛋白的表达，缓解缺氧复氧诱导的心肌 细胞损伤。

Objective To investigate the reparative effect of astragaloside IV on hypoxia-reoxygenation-induced cardiomyocyte injury by regulating the thioredoxin-interacting protein（TXNIP）-Nod-like receptor protein 3 （NLRP3） pathway. Methods H9c2 cardiomyocytes were divided into control group，hypoxia-reoxygenation group， astragaloside IV low- and high-dose groups，astragaloside IV high-dose + pcDNA-NC group，and astragaloside IV high-dose + pcDNA-TXNIP group. After intervention， H9c2 proliferation was measured by Cell Counting Kit 8 （CCK-8） assay， apoptosis was detected by flow cytometry， lactate dehydrogenase（LDH） and superoxide dismutase（SOD） activities were determined by WST-8 assay，probebyreactive oxygen species（ROS） generation was measured by 2’，7’-dichlorodihydrofluorescein diacetate （DCFDA） fluorescent， enzyme-linked inmunosorbent assay （ELISA） was used to quantify interleukin 6（IL-6） and tumor necrosis factor α（TNF- α） levels，Western Blot was used to analyze the protein expression of TXNIP and NLRP3. Results Compared with the control group，the hypoxia-reoxygenation group showed significantly decreased cell survival rate and SOD activity （P＜0.05），with increased apoptosis rate，LDH level，ROS generation，IL-6 and TNF-α levels，and protein expression levels of TXNIP and NLRP3（P＜0.05）. Compared with the hypoxia-reoxygenation group， the cell survival rate and SOD activity in the low-dose and high-dose astragaloside IV groups were significantly increased （P＜0.05）， and the apoptosis rate， LDH level， ROS production， IL-6 and TNF- α levels and protein expression levels of TXNIP and NLRP3 were significantly decreased（P＜0.05）. Compared with the high-dose astragaloside IV + pcDNA-NC group，the cell survival rate and SOD activity in the high-dose astragaloside IV + pcDNA-TXNIP group were significantly decreased（P＜0.05）， and the apoptosis rate， LDH level， ROS production， IL-6 and TNF- α levels and protein expression levels of TXNIP and NLRP3 were significantly increased（P＜0.05）. Conclusion Astragaloside IV may alleviate hypoxia-reoxygenation-induced cardiomyocyte damage by downregulating key proteins in the TXNIP-NLRP3 pathway.

R285.5

国家重点研发项目（编号：2019YFC1710604）；首都医科大学附属北京中医医院院级课题重点项目（编号：LYZD202204）