Department of Intensive Medicine, The Third Hospital of Nanchang, Nanchang, Jiangxi, China.
Department of Intensive Medicine, Ruian People's Hospital, No. 108 Wansong Road, Yuhai Street, Ruian, Wenzhou, 325200, Zhejiang, China.
Biol Res. 2019 May 13;52(1):29. doi: 10.1186/s40659-019-0236-5.
Acute kidney injury (AKI), which is mainly caused by sepsis, has high morbidity and mortality rates. CXCL8 K11R/G31P (G31P) can exert therapeutic effect on inflammatory diseases and malignancies. We aimed to investigate the effect and mechanism of G31P on septic AKI.
An AKI mouse model was established, and kidney injury was assessed by histological analysis. The contents of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured by commercial kits, whereas neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were detected by enzyme-linked immunosorbent assay (ELISA) kits. The expressions of CXCL8 in serum and kidney tissues were determined using ELISA and immunohistochemical analysis, respectively. Apoptosis rate of renal tissue was detected by terminal deoxynucleotidyl transfer-mediated dUTP nick end labeling (TUNEL) analysis. The expressions of inflammatory cytokines were measured by quantitative real-time PCR and Western blot, respectively. The apoptosis-related proteins, JAK2, STAT3, NF-κB and IκB were determined by Western blot.
G31P could reduce the levels of SCr, BUN, HGAL and KIM-1 and inhibit the renal tissue injury in AKI mice. G31P was also found to suppress the serum and nephric CXCL8 expressions and attenuated the apoptosis rate. The levels of inflammatory cytokines, pro-apoptotic proteins were decreased, while the anti-apoptotic proteins were increased by G31P in AKI mice. G31P also inhibited the activation of JAK2, STAT3 and NF-κB in AKI mice.
These results suggest that G31P could protect renal function and attenuate the septic AKI. Our findings provide a potential target for the treatment of AKI.
急性肾损伤（AKI）主要由脓毒症引起，其发病率和死亡率均较高。趋化因子（C-X-C）配体 8 趋化因子 11 受体丝氨酸 11 精氨酸 31 脯氨酸（G31P）可对炎症性疾病和恶性肿瘤发挥治疗作用。本研究旨在探讨 G31P 对脓毒症性 AKI 的作用及机制。
建立 AKI 小鼠模型，通过组织学分析评估肾损伤。采用商业试剂盒测定血清肌酐（SCr）和血尿素氮（BUN）含量，酶联免疫吸附试验（ELISA）试剂盒测定中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和肾损伤分子 1（KIM-1）的含量。ELISA 和免疫组织化学分析分别检测血清和肾组织中 CXCL8 的表达。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）分析检测肾组织的凋亡率。定量实时 PCR 和 Western blot 分别测定炎症细胞因子的表达。Western blot 测定凋亡相关蛋白 JAK2、STAT3、NF-κB 和 IκB 的表达。
G31P 可降低 AKI 小鼠的 SCr、BUN、NGAL 和 KIM-1 水平，抑制肾组织损伤。还发现 G31P 可抑制 AKI 小鼠血清和肾组织中 CXCL8 的表达，降低其凋亡率。G31P 还降低了 AKI 小鼠中促凋亡蛋白的水平，增加了抗凋亡蛋白的水平。G31P 还抑制了 AKI 小鼠中 JAK2、STAT3 和 NF-κB 的激活。
这些结果表明，G31P 可保护肾功能，减轻脓毒症性 AKI。本研究结果为 AKI 的治疗提供了一个潜在靶点。
