Acute kidney injury (AKI) is a major complication of sepsis. Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes are multiprotein complexes that mediate septic AKI. L-arginine (Arg) is a conditionally essential amino acid in catabolic conditions and a substrate for nitric oxide (NO) production; however, its use in sepsis is controversial. This study investigated the effect of intravenous Arg supplementation on modulating NLRP3 inflammasome activity in relation to septic AKI. Mice were divided into normal control (NC), sham, sepsis saline (SS), and sepsis Arg (SA) groups. In order to investigate the role of NO, L-N6-(1-iminoethyl)-lysine hydrochloride (L-NIL), an inducible NO synthase inhibitor, was administered to the sepsis groups. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg via tail vein 1 h after CLP. Mice were sacrificed at 6, 12, and 24 h after sepsis. The results showed that compared to the NC group, septic mice had higher plasma kidney function parameters and lower Arg levels. Also, renal NLRP3 inflammasome protein expression and tubular injury score increased. After Arg treatment, plasma Arg and NO levels increased, kidney function improved, and expressions of renal NLRP3 inflammasome-related proteins were downregulated. Changes in plasma NO and renal NLRP3 inflammasome-related protein expression were abrogated when L-NIL was given to the Arg sepsis groups. Arg plus L-NIL administration also attenuated kidney injury after CLP. The findings suggest that intravenous Arg supplementation immediately after sepsis restores plasma Arg levels and is beneficial for attenuating septic AKI, partly via NO-mediated NLRP3 inflammasome inhibition.

中文翻译：

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静脉内精氨酸管理下调具有微生物败血症的小鼠的NLRP3炎性体活性并减轻急性肾脏损伤。

急性肾损伤（AKI）是脓毒症的主要并发症。核苷酸结合域样受体蛋白3（NLRP3）炎性小体是介导败血症AKI的多蛋白复合物。L-精氨酸（Arg）是分解代谢条件下的条件必需氨基酸，是一氧化氮（NO）生产的底物；但是，其在脓毒症中的使用引起争议。这项研究调查了静脉注射精氨酸补充剂对脓毒症AKI调节NLRP3炎症小体活性的影响。将小鼠分为正常对照组（NC），假手术，败血症盐水（SS）和败血症Arg（SA）组。为了研究NO的作用，对败血症组给予L-N6-（1-亚氨基乙基）-赖氨酸盐酸盐（L-NIL），其为诱导型NO合酶抑制剂。使用盲肠结扎穿刺术（CLP）诱发败血症。CLP后1 h，SS和SA组通过尾静脉接受盐水或Arg。在败血症后6、12和24小时处死小鼠。结果表明，与NC组相比，败血症小鼠的血浆肾功能参数更高，Arg水平更低。同样，肾脏NLRP3炎性小体蛋白表达和肾小管损伤评分增加。精氨酸治疗后，血浆精氨酸和一氧化氮水平升高，肾脏功能改善，肾脏NLRP3炎性小体相关蛋白的表达下调。将L-NIL给予Arg败血症组后，血浆NO和肾脏NLRP3炎性小体相关蛋白表达的变化被消除。精氨酸加L-NIL的给药也减轻了CLP后的肾脏损伤。