高迁移率族蛋白B1在失血性休克致急性肺损伤中的作用

目的 探讨高迁移率族蛋白 B1(high mobility group box1,HNGB1)在失血性休克(hemarrhag-ic shock,HS)所致急性肺损伤(acute lung injury,ALI)小鼠体内的变化和意义.方法健康雄性BALB/c小鼠42只,随机分为对照组、HS致ALI组和抗HMGB1抗体干预组.心脏穿刺抽血复制小鼠HS致ALI模型,酶联免疫吸附(ELISA)法检测肺组织IL-1β,TNF-α,Westemblot检测肺组织HMGB1,比色法检测肺组织髓过氧化物酶(MPO)、伊文蓝(EBD),观察肺脏病理变化.统计学采用方差分析及LSD-t检验.结果 HS后2 h即可见肺血管通透性增高,肺脏出现弥漫件炎细胞侵润.肺绀织IL-1β和TNF-α在HS诱导的ALI早期(4 h)升高[IL-1β(333.83±31.18)vs.(284.83±30.49),P=0.014;TNF-α(805.00±114.67)vs.(584.17±181.17),P=0.023];肺组织HMCB1在ALI 16～48 h显著升高[HMGB1/β-actin(0.99±0.16)vs.(0.50±0.18),P=0.003].ALI组小鼠肺MPO及EBD水平显著增高,分别于ALI 4 h和24 h达峰值[MPO(38.33±3.88)vs.(8.00±0.89),P<0.01;EBD(20.05±2.79)vs.(4.63±0.43),P<0.01];抗HMGB1抗体干预组肺组织MPO及EBD峰值显著下降[MPO(25.67±1.63)vs.(38.33±3.88),P<0.01;EBD(5.68±0.53)vs.(20.05±2.79),P<0.01],抗体干预组小鼠肺组织病理切片见肺部弥漫性炎细胞浸润减轻,抗体干预24 h组尤为明显.结论 HNGB1是HS所致ALI的晚期炎症介质,HNGBl拮抗治疗能减轻小鼠HS所致ALI病理牛理改变.

Role of high mobility group box1 in hemorrhagic shock-induced acute lung injury

Objective To investigate the role of high mobility group box1 (HMGB1) in hemorrhagic shock-induced acute lung injury (ALI) in mouse model. Method Forty-two healthy male BALB/c mice were randomly divided into three groups: control group, hemorrhagic shock (HS) group and anti-HMGB1 treatmeut group. Car-diac puncture, was performed to induce ALI in mice. IL-β and TNF-α in lung tissues were detected by ELISA. Ex-pression of HMGB1 was determined by Westemblot. Myeloperoxidase (MPO) and Evens blue dye (EBD) in lung tissues were measured by colorimetry. Pathology of lung tissue was observed. ANOVA and LSD-t test were used in statistical analysis. Results Pulmonary blood vessel permeability increased 2 h after HS, pathology results re-vealed a diffused inflammatory cell infiltration in mouse lung tissue. Levels of IL-1β and TNF-α in lung tissues sig-nificantly increased at the early stage of ALI (4 h) compared to controls [IL-1β(333.83±31.18) vs. (284.83± 30.49), P =0.014; TNF-α(805.00±114.67) vs. (584.17±181.17), P =0.023]. Significant increase of HMGB1 in lung tissues occurred at the late stage of ALI (16～48 h) [HMGB1/β-actin (0.99±0.16) vs. (0.50 ±0.18), P =0.003]. The levels of MPO and EBD in ALl group significantly increased compared to controls, and reached the peak at4 h and 24 h respectively [MPO (38.33±3.88) vs. (8.00±0.89), P <0.01;EBD (20.05±2.79) vs. (4.63±0.43), P <0.01]. The peak level of MPO and EBD significantly decreased in anti-HMGB1 groups compared to that of ALI group [MPO (25.67±1.63) vs. (38.33±3.88), P < 0.01 ; EBD (5.68±0.53) vs. (20.05±2.79), P <0.001]. The infiltration of neutrophils and the destruction of the pul-monary cell walls ameliorated in anti-HMGB1 groups, especially in mice treated with anti-HMGB1 antihedy for 24 h. Conclusions HMGBI acts as a late pminfiammatory mediator in HS-induced ALI. Blockade of HMGB1 de-creases HS-induced pathophysiologic change of ALI in mice.