Protectin DX对小鼠脓毒症致急性肾损伤的保护作用及其相关机制  

Protectin DX Ameliorates Acute Kidney Injury Induced by Sepsis in Mice

作　　者：夏海发[1,2] 孙志鹏[1] 崔术楠[1] 尚游[1,3] 姚尚龙[1,2] 

机构地区：[1]华中科技大学同济医学院附属协和医院麻醉与危重病医学研究所,武汉430022 [2]华中科技大学同济医学院附属协和医院麻醉科,武汉430022 [3]华中科技大学同济医学院附属协和医院ICU,武汉430022

出　　处：《华中科技大学学报（医学版）》2016年第1期39-42,48,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81372036)

摘　　要：目的探讨脂质介质Protectin DX(PDX)对脓毒症小鼠急性肾损伤的保护作用及其相关机制。方法雄性C57BL/6小鼠随机分为3组(n=10),假手术组(S组),脓毒症组(CLP组)和脓毒症+PDX干预组(PDX组)。采用盲肠结扎穿孔法模拟脓毒症模型。PDX组在CLP造模后1h给予腹腔注射PDX 300ng,S组和CLP组均给予等量生理盐水腹腔注射。3组均在CLP术后24h收集全血清、肾组织标本,采用苏木精-伊红(HE)染色观察肾组织病理变化并进行肾损伤评分;采用全自动生化分析仪检测血清中肌酐(Cr)和尿素氮(BUN)水平;ELISA检测血清中的IL-1β、TNF-α、IL-6和IL-10水平;Western blot检测肾组织中NF-κB活性。结果与S组相比,CLP组肾损伤病理评分增高(P<0.05);血清中的Cr、BUN、IL-1β、TNF-α、IL-6和IL-10水平均明显升高(均P<0.05);肾组织中NF-κB活性显著增强(P<0.05)。PDX组与CLP组相比,肾损伤病理评分降低(P<0.05);血清中的Cr、BUN、IL-1β、TNF-α和IL-6水平均降低,抗炎因子IL-10水平升高,肾组织NF-κB活性明显抑制(均P<0.05)。结论 PDX可通过抑制NF-κB活性减少炎症因子水平,进而缓解小鼠脓毒症诱导的急性肾损伤。Objective To explore the protective role of protectin DX（PDX）in acute kidney injury（AKI）induced by sepsis in mice and the underlying mechanism.Methods Male C57BL/6 mice were randomly divided into 3groups（n=10each）：sham group,sepsis group and sepsis＋PDX group（PDX group）.Sepsis models were established by cecal ligation and puncture（CLP）.Mice in PDX group were intraperitoneally given 300 ng PDX one h after CLP,while those in other groups received equal amounts of saline in the same manner.The serum and kidney tissues were collected 24 hafter CLP.The histological changes of the kidney were observed by HE staining and kidney injuries were scored.The Cr and BUN levels in the serum were assessed by using the automatic biochemical analyzer.ELISA was used to measure the levels of cytokines（IL-1β,TNF-α,IL-6and IL-10）and Western blotting to detect the NF-κB activity in the kidney tissue.Results The kidney injury score,serum levels of Cr,BUN,IL-1β,TNF-α,IL-6and IL-10,and the activity of NF-κB in the kidney were significantly increased in sepsis group when compared with those in sham group（P〈0.05）.These indices were significantly improved in PDX group as compared with those in sepsis group（P〈0.05）.Conclusion PDX could alleviate AKI in septic mice through inhibiting NF-κB activity and decreasing the inflammatory response.

关 键 词：Protectin DX 脓毒症 急性肾损伤 NF-ΚB 

分 类 号：R151.3[医药卫生—营养与食品卫生学]