磷脂酶A_2抑制剂溴苯乙酮对大鼠急性失血性休克复苏后早期肺损伤的保护作用

Protective effects of phospkolipase A_2 antagonist 4-bromophennacyl bromide on acute lung injury following hemorrhagic shock and resuscitation in rats

目的观察磷脂酶Ａ_２抑制剂４－二溴苯乙酮（４－ＢＰＢ）对大鼠急性失血性休克复苏后早期肺损伤的保护作用。方法纯种ＳＤ大鼠３６只，随机分为假手术组（对照组）、乳酸林格氏液复苏组（ＬＲ组）、乳酸林格氏液＋４－ＢＰＢ复苏组（保护组）。两复苏组动物放血并维持低血压（ＭＡＰ ４～５．３ｋＰａ） ６０分钟，其后１０分钟内分别输入全部自体抗凝血或同时静注４－ＢＰＢ（２５μｍｏｌ）；２０分钟内输入２倍放血量的乳酸林格氏液，观察６０分钟。实验结束时收集血清、肺组织标本或作支气管肺泡灌洗。双缩脲法测定支气管肺泡灌洗液（ＢＡＬＦ）及血清中蛋白的浓度；放免法检测血清中ＴＮＦａ、ＩＬ－１β、ＩＬ－６及ＩＬ－８水平。光镜下比较观察各组大鼠肺组织形态学改变。结果保护组血清ＴＮＦα水平明显低于 ＬＲ组（Ｐ＜０． ０１），而与对照组无明显差异。三组血清ＩＬ－１β，ＩＬ－６及ＩＬ－８水平除ＬＲ组ＩＬ－６与对照组比较有明显差别外，其余则均无明显差异。保护组肺通透指数与对照组比较无显著性差异，而ＬＲ组明显高于其它两组（Ｐ＜０．０１）。支气管肺泡灌洗液中蛋白含量ＬＲ组明显高于其它两组，保护组明显高于对照组（Ｐ＜０．０１）。

Objective To evaluate the protective effects of 4-bromophennacyl bromide (4BPB)on acute lung injury following hemorrhagic shock and resuscitation. Methods Thirty-six rats were randomly divided into three groups: control group, LR group and 4-BPB group (n=12 for each). In control group hemorrhage did not occur, but in LR or 4-BPB group the hemorrhagic shock was induced with bleeding to maintaine MAP at 4 to 5.3 kPa for 60 min, then resuscitated with the shed blood and lactated Ringer's (LR) solution or shed blood, 25μmol of 4-BPB and LR over 30 min. The serum levels of TNFQ, IL-1β, IL-6 and IL-8, and the protein concentrations of serum and bronchoalveolar lavage fluid (BALF) were measured 60 min following resuscitation. In the end of the experiments, lungs of the animals were preserved for histologic examination. Results The serum TNFα level and lung permeability index were significantly lower in 4-BPB group than that in LR group (P<0. 01), without significant difference in them between control and 4-BPB groups (P> 0.05). The protein concentration of BALF markedly increased in LR and 4-BPB groups as compared with control level (P<0. 01), but the level was significantly lower in 4-BPB group than that in LR group (P<0.01). There was a slighter morphologic appearance in 4-BPB group than in LR group. Conclusion The acute lung injury occurs following acute hemorrhagic shock and resuscitation through activation of PLA_2. Administration with PLA_2 inhibitor (4-BPB) can effectively prevent the injury from occurrance.