Objective. Renal ischemia/reperfusion injury (RI/RI) is the main cause of acute kidney injury. Total glucosides of paeony (TGP) are a traditional Chinese medicine. This study was aimed at exploring the role of TGP in RI/RI and its underlying mechanism of action. Methods. Rat RI/RI models were constructed by surgical operation. Serum creatinine (Scr) and blood urea nitrogen (BUN) were used to evaluate renal function. The levels of proinflammatory cytokines were detected by ELISA. RI/RI was simulated by hypoxia/reoxygenation (H/R) treatment in renal cells in vitro. The lncRNA XIST (XIST) expression was analyzed by qRT-PCR. Then, the viability and apoptosis of renal cells were detected by MTT and flow cytometry assay. Additionally, dual-luciferase reporter assay was used to determine the interactions among XIST, microRNA-124-3p (miR-124-3p), and ITGB1. Results. TGP improved renal function and inhibited inflammatory responses after RI/RI. XIST expression was highly expressed in rat RI/RI models and H/R-treated renal cells, whereas treatment with TGP downregulated the XIST expression. Additionally, TGP increased viability and attenuated apoptosis and inflammation of H/R-treated renal cells via inhibiting XIST. Moreover, XIST was competitively bound to miR-124-3p, and ITGB1 was a target of miR-124-3p. miR-124-3p overexpression or ITGB1 inhibition rescued the reduction effect on viability and mitigated the promoting effects on cell apoptosis and inflammation caused by XIST overexpression in H/R-treated renal cells. Conclusions. In vivo, TGP attenuated renal dysfunction and inflammation in RI/RI rats. In vitro, TGP inhibited XIST expression to modulate the miR-124-3p/ITGB1 axis, alleviating the apoptosis and inflammation of H/R-treated renal cells.

中文翻译：

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白芍总苷通过靶向长非编码RNA XIST/MicroRNA-124-3p/ITGB1轴减轻肾缺血/再灌注损伤中的细胞凋亡和炎症


客观的。肾缺血/再灌注损伤（RI/RI）是急性肾损伤的主要原因。白芍总苷（TGP）是一种传统中药。本研究旨在探讨TGP在RI/RI中的作用及其潜在作用机制。方法。通过外科手术构建大鼠RI/RI模型。血清肌酐（Scr）和血尿素氮（BUN）用于评估肾功能。采用ELISA法检测促炎细胞因子的水平。 RI/RI是通过体外肾细胞缺氧/复氧(H/R)处理来模拟的。通过 qRT-PCR 分析 lncRNA XIST (XIST) 表达。然后通过MTT和流式细胞术检测肾细胞的活力和凋亡。此外，使用双荧光素酶报告基因测定来确定 XIST、microRNA-124-3p (miR-124-3p) 和 ITGB1 之间的相互作用。结果。 TGP 改善肾功能并抑制 RI/RI 后的炎症反应。 XIST 表达在大鼠 RI/RI 模型和 H/R 处理的肾细胞中高表达，而 TGP 处理下调 XIST 表达。此外，TGP 通过抑制 XIST 增加了 H/R 处理的肾细胞的活力并减轻了细胞凋亡和炎症。此外，XIST 竞争性地结合 miR-124-3p，而 ITGB1 是 miR-124-3p 的靶标。在 H/R 处理的肾细胞中，miR-124-3p 过表达或 ITGB1 抑制挽救了对活力的降低作用，并减轻了 XIST 过表达引起的细胞凋亡和炎症的促进作用。结论。在体内，TGP 可减轻 RI/RI 大鼠的肾功能障碍和炎症。 在体外，TGP 抑制 XIST 表达，调节 miR-124-3p/ITGB1 轴，减轻 H/R 处理的肾细胞的凋亡和炎症。