Background Hyperhomocysteinemia (HHcy) plays an important role in the progression of many kidney diseases; however, the relationship between HHcy and ischemia-reperfusion injury (IRI)-induced acute kidney injury (IRI-induced AKI) is far from clear. In this study, we try to investigate the effect and possible mechanisms of HHcy on IRI-induced AKI. Methods Twenty C57/BL6 mice were reared with a regular diet or high methionine diet for 2 weeks (to generate HHcy mice); after that, mice were subgrouped to receive sham operation or ischemia-reperfusion surgery. Twenty four hour after reperfusion, serum creatinine, blood urea nitrogen, and Malondialdehyde (MDA) were measured. H&E staining for tubular injury, western blot for γH2AX, JNK, p-JNK, and cleaved caspase 3, and TUNEL assay for tubular cell apoptosis were also performed. Results Our results showed that HHcy did not influence the renal function and histological structure, as well as the levels of MDA, γH2AX, JNK, p-JNK, and tubular cell apoptosis in control mice. However, in IRI-induced AKI mice, HHcy caused severer renal dysfunction and tubular injury, higher levels of oxidative stress, DNA damage, JNK pathway activation, and tubular cell apoptosis. Conclusion Our results demonstrated that HHcy could exacerbate IRI-induced AKI, which may be achieved through promoting oxidative stress, DNA damage, JNK pathway activation, and consequent apoptosis.

中文翻译：

---

高同型半胱氨酸血症通过介导氧化应激、DNA损伤、JNK通路和细胞凋亡加剧缺血再灌注损伤诱导的急性肾损伤

背景高同型半胱氨酸血症（HHcy）在许多肾脏疾病的进展中起重要作用；然而，HHcy 与缺血再灌注损伤 (IRI) 诱发的急性肾损伤 (IRI-induced AKI) 之间的关系尚不清楚。在这项研究中，我们试图研究 HHcy 对 IRI 诱导的 AKI 的影响和可能的机制。方法 20只C57/BL6小鼠采用常规饮食或高蛋氨酸饮食饲养2周（产生HHcy小鼠）；之后，将小鼠分组接受假手术或缺血再灌注手术。再灌注后 24 小时，测定血清肌酐、血尿素氮和丙二醛 (MDA)。还进行了肾小管损伤的 H&E 染色、γH2AX、JNK、p-JNK 和切割的半胱天冬酶 3 的蛋白质印迹，以及肾小管细胞凋亡的 TUNEL 测定。结果我们的结果表明，HHcy不影响对照小鼠的肾功能和组织学结构，以及MDA、γH2AX、JNK、p-JNK和肾小管细胞凋亡的水平。然而，在 IRI 诱导的 AKI 小鼠中，HHcy 导致更严重的肾功能障碍和肾小管损伤、更高水平的氧化应激、DNA 损伤、JNK 通路激活和肾小管细胞凋亡。结论 我们的研究结果表明，HHcy 可加剧 IRI 诱导的 AKI，这可能通过促进氧化应激、DNA 损伤、JNK 通路激活和随后的细胞凋亡来实现。更高水平的氧化应激、DNA 损伤、JNK 通路激活和肾小管细胞凋亡。结论 我们的研究结果表明，HHcy 可加剧 IRI 诱导的 AKI，这可能通过促进氧化应激、DNA 损伤、JNK 通路激活和随后的细胞凋亡来实现。更高水平的氧化应激、DNA 损伤、JNK 通路激活和肾小管细胞凋亡。结论 我们的研究结果表明，HHcy 可加剧 IRI 诱导的 AKI，这可能通过促进氧化应激、DNA 损伤、JNK 通路激活和随后的细胞凋亡来实现。