线粒体靶向抗氧化剂 SS-31肽对脓毒血症小鼠急性肺损伤的影响

摘要

目的：观察线粒体靶向抗氧化剂 SS-31肽对小鼠脓毒血症引起急性肺损伤(ALI)的影响。方法采用盲肠结扎穿孔法(CLP)建立小鼠脓毒症模型。成年雄性 C57BL/6小鼠48只,体重25~32 g,随机均分为四组：假手术+溶剂组(A 组)、假手术+ SS-31肽组(B 组)、CLP+溶剂组(C组)及 CLP+SS-31肽组(D 组)。于术后即刻及5 h B、D 组腹腔注射 SS-31肽5 mg/kg,A、C 组腹腔注射等容剂量的生理盐水。假手术或 CLP 24 h 后,采用 HE 染色法进行肺组织学评分,取肺组织检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10、丙二醛(MDA)、超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)活性、干湿重比(W/D)、活性氧簇(ROS)、ATP 水平、核转录因子κB(NF-κB)p65、诱导性一氧化氮合酶(iNOS)表达。结果 C 组肺炎症渗出、水肿程度均明显重于 A 组(P <0.05), D 组肺组织充血、炎性细胞浸润、肺泡壁水肿明显轻于 C 组(P <0.05)；C 组肺组织学评分、IL-6浓度、MDA、MPO、W/D、ROS 水平、NF-κB p65及 iNOS 表达明显高于 A 组,ATP 水平明显低于 A 组(P <0.05)；D 组肺组织学评分、IL-6浓度、MDA、MPO、W/D、ROS 水平、NF-κB p65及 iNOS 表达明显低于 C 组,ATP 水平明显高于 C 组(P <0.05)。A 组与 B 组各项指标差异无统计学意义。四组肺组织 TNF-α、IL-10浓度及 SOD 水平差异无统计学意义。结论 SS-31肽可改善小鼠脓毒血症引起的 ALI,这可能是通过抑制脓毒血症的炎性反应和氧化应激实现的。%Objective To investigate the effects of antioxidant SS-31 on sepsis-induced acute lung injury (ALI)in a mouse model of sepsis.Methods Sepsis was induced in male mice by cecal liga-tion and puncture (CLP).Forty-eight adult male mice (C57BL/6,weight 25-32 g)were equally as-signed to the sham+vehicle group (group A),sham+SS-31 group (group B),CLP+vehicle group (group C),or the CLP+SS-31 group (group D).At 0 or 5 h after CLP or sham operation,mice re-ceived an intraperitoneal injection of SS-31 (5 mg/kg of body weight)or the same volume of normal saline.Pulmonary tumor necrosis factor alpha (TNF-α),interleukin (IL)-6,IL-10,malondialdehyde (MDA),superoxide dismutase activities (SOD),myeloperoxidase activities (MPO ),wet-to-dry weight ratio (W/D),reactive oxygen species (ROS),ATP,NF-κB p65,inducible nitric oxide syn-thase (iNOS),and histological scores were assessed 24 h after operation.Results Pneumonia,edema were significantly heavier in group C than in group A (P <0.05).Lung congestion,inflammatory cell infiltration,alveolar wall edema was significantly less in group D than in group C (P <0.05).Pulmo-nary histological scores,IL-6,MDA,MPO,W/D,ROS,NF-κB p65 and iNOS significantly in-creased,while ATP levels decreased in group C when compared with group A (P <0.05).However, SS-31 treatment significantly reversed these parameters when compared with the group C (P <0.05). No difference was observed between the group A and group B.There was no difference of TNF-α,IL-10,and SOD among the four groups.Conclusion SS-31 improves sepsis-induced ALI in a mouse model probably by down-regulating the oxidative stress and inflammation in of sepsis-induced ALI.