脑肠肽对脓毒症相关性肾损伤的保护作用研究

目的 探讨脑肠肽对内毒素所致大鼠脓毒症相关性肾损伤的影响.方法 健康雄性SD大鼠36只,随机分为3组：正常对照组,急性肾损伤（acute kidney injury,AKI）组,脑肠肽治疗组.采用内毒素静注制备脓毒症AKI模型,脑肠肽治疗组于造模前后30 min给予皮下注射脑肠肽（1.0mg/kg）,选择不同时间点（6 h、12 h、24 h）处死动物后留取血标本和肾组织,检测血清肌酐（SCr）、尿素氮（BUN）、血清肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）、观察肾组织的病理变化并检测肾脏组织中核因子κB的活化.结果 与同时间点比较,AKI组6h和12 h大鼠血清中TNF-α表达水平明显升高（P＜0.01）,24 h降至对照组水平（P＞0.05）,AKI组6h、12 h和24 h大鼠血清中BUN水平逐渐升高（P＜0.05）,24 h血清中SCr水平明显升高（P＜0.01）;AKI组24 h大鼠肾脏组织核因子κB p65核阳性率明显升高（P＜0.01）.脑肠肽治疗组对应时间点血清BUN和SCr水平较AKI组明显降低（P＜0.01）.TNF-α和核因子κB p65表达明显低于AKI组（P＜0.01）.病理显示脑肠肽治疗组大鼠肾损伤减轻,SCr、BUN、TNF-α、光镜检查均未见明显差异.结论 脑肠肽可通过抑制肾组织核因子κB的表达,下调TNF水平,对脓毒症相关性肾损伤发挥保护作用.

An experiment study of the protective effects of ghrelin on acute kidney injury induced by sepsis

Objective To discuss the influence of ghrelin on acute kidney injury（AKI） which induced by sepsis.Methods 36 cases of healthy and male SD rats were randomly divided into 3 groups （n=12/group）：control group,AKI group and ghrelin group.AKI model were established by intravenous injection of LPS,ghrelin group were subcutaneously given ghrelin （1.0 mg/kg） before and after LPS injection.We choose different time points（6 h,12 h,24 h） executed animals to get blood and kidney tissues,detection of serum creatinine,urea nitrogen,serum tumor necrosis factor alpha（TNF-α）,observe the pathological changes of the kidney,pathological grading,and examine the activation of nuclear factor-κB in kidney tissue.Results Compared with the same time point in time,the TNF-α expression level were increased significantly（P＜0.01）at 6 h and 12 h after the LPS injection,the serum BUN level were increased significantly at 6 h,12 h and 24 h（P＜0.05）.24 h SCr in serum level were significantly increased in AKI group compared with control group （P＜0.01）.AKI group 24 h in the rat kidney tissue NF-κB p65 nuclear positive rate increased significantly（P＜0.01）.Ghrelin level of BUN and SCr group corresponding time points from AKI group significantly decreased （P＜0.01）.TNF alpha and NF-κB p65 expression was lower than that in group AKI（P＜0.01）.Pathology revealed ghrelin group in the rat kidney injury,score below AKI group（P＜0.05）,Ghrelin group compared with control group,renal function,serum inflammatory factor,there were no significant differences.Conclusions Ghrelin can alleviate AKI induced by sepsis in rat via down regulating levels of TNF and inhibiting of activity of NF-κB in renal tissues.