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CXCL8(3-72) K11R/G31P protects against sepsis-induced acute kidney injury via NF-κB and JAK2/STAT3 pathway.
Biological Research ( IF 6.7 ) Pub Date : 2019-05-13 , DOI: 10.1186/s40659-019-0236-5
Yunfeng Zhou 1 , Wenda Xu 1 , Hong Zhu 2
Affiliation  

BACKGROUND Acute kidney injury (AKI), which is mainly caused by sepsis, has high morbidity and mortality rates. CXCL8(3-72) 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. METHODS 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. RESULTS 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. CONCLUSION 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.

中文翻译:

CXCL8(3-72)K11R / G31P通过NF-κB和JAK2 / STAT3途径预防败血症引起的急性肾脏损伤。

背景技术主要由败血症引起的急性肾损伤(AKI)具有高发病率和死亡率。CXCL8(3-72)K11R / G31P(G31P)可对炎性疾病和恶性肿瘤发挥治疗作用。我们旨在研究G31P对败血性AKI的作用和机制。方法建立AKI小鼠模型,通过组织学分析评估肾脏损伤。用商业试剂盒测定血清肌酐(SCr)和血尿素氮(BUN)的含量,而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)的含量通过酶联免疫吸附法检测( ELISA)试剂盒。分别通过ELISA和免疫组化分析确定CXCL8在血清和肾脏组织中的表达。通过末端脱氧核苷酸转移介导的dUTP缺口末端标记(TUNEL)分析检测肾组织的凋亡率。分别通过实时定量PCR和Western blot检测炎性细胞因子的表达。Western blot法检测凋亡相关蛋白JAK2,STAT3,NF-κB和IκB。结果G31P可以降低AKI小鼠的SCr,BUN,HGAL和KIM-1水平,并抑制肾脏组织损伤。还发现G31P抑制血清和肾CXCL8表达,并降低细胞凋亡率。G31P能使AKI小鼠的炎症细胞因子,促凋亡蛋白水平降低,而抗凋亡蛋白水平升高。G31P还抑制了AKI小鼠中JAK2,STAT3和NF-κB的激活。结论这些结果表明,G31P可以保护肾脏功能并减轻败血性AKI。我们的发现为AKI的治疗提供了潜在的目标。
更新日期:2020-04-22
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