C1q/肿瘤坏死因子相关蛋白6(CTRP6)介导庆大霉素所致大鼠急性肾损伤

C1q/tumor necrosis factor related protein 6(CTRP6) is involved in gentamicininduced acute kidney injury in rats

目的探讨抗炎细胞因子C1q/肿瘤坏死因子相关蛋白6(CTRP6)在庆大霉素所致急性肾损伤(AKI)中的作用。方法SD大鼠分为5组,对照组、模型组和3个实验组。模型组和实验组皮下注射庆大霉素400 mg/(kg·d),连续注射2 d,建立庆大霉素中毒性AKI动物模型;3个实验组大鼠在注射庆大霉素前2 d,分别给予(0.5、5、50)mg/kg的CTRP6腺病毒表达载体。苦味酸比色法检测肌酐(Cr)含量,紫外分光光度法检测血清尿素氮(BUN)含量,ELISA检测血清CTRP6的水平以及肾组织匀浆中白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的水平。Western blot法检测肾脏组织中CTRP6、NOD样受体家族含pyrin结构域蛋白3(NLRP3)和caspase-1的表达。结果与对照组相比,模型组大鼠AKI指标血清BUN和Cr水平较对照组显著增高,炎症因子IL-1β和TNF-α的分泌量以及NLRP3和caspase-1蛋白表达水平也显著增加。与模型组相比,实验组大鼠血清BUN和Cr水平降低,IL-1β和TNF-α的分泌减少,NLRP3和caspase-1的表达水平下降。随着注射CTRP6腺病毒表达载体注射剂量的增加,抑制效果逐渐增强。结论 CTRP6以剂量依赖的方式减弱庆大霉素所致的大鼠急性肾功能损伤。

Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6（CTRP6） in gentamicin-induced acute kidney injury in rats.Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups.The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg /（kg·d） for consecutive 2 days to induce acute renal injury.Two days before gentamicin injection,the rats in the 3 experimental groups were given p Ad-CTRP6 at the doses of 0.5,5and 50 mg/kg,respectively.The serum levels of blood urea nitrogen（BUN） and creatinine（Cr） were respectively assayed with picric acid colorimetry and ultraviolet spectrophotometry; ELISA was used to detect serum CTRP6 content and the production of interleukin 1β（IL-1β） and tumor necrosis factor α（TNF-α） in the kidney homogenate; Western blotting was performed to detect the expressions of CTRP6,caspase-1 and pyrin domain containing 3（NLRP3） proteins in the renal tissues of rats.Results Compared with control group,serum BUN and Cr contents increased in the model rats; the secretion of inflammatory factors IL-1β and TNF-α,as well as the expressions of caspase-1 and NLRP3 were also enhanced in the model group.Compared with the model group,serum BUN and Cr contents decreased in the experimental groups; the secretion of IL-1β and TNF-α,as well as the expressions of caspase-1 and NLRP3 were also attenuated in the experimental groups.Moreover, with the increase of the injection dosage of p Ad-CTRP6, the suppressive effect was gradually strengthened.Conclusion CTRP6 can attenuate gentamicin-induced acute renal injury in rats in a dose-dependent manner.