机械通气对急性胰腺炎大鼠肺组织病理及巨噬细胞炎性介质的影响

Effects of mechanical ventilation on lung tissue pathology and proinflammatory cytokines responses in acute pancreatitis rats

目的探讨保护性机械通气对急性坏死性胰腺炎(ANP)-肺损伤大鼠肺组织病理和肺泡炎性细胞介质的影响。方法 45只SD大鼠预处理诱导ANP-肺损伤模型,按照ANP和机械通气干预随机分成三组(每组15只):A组,对照组;B组,ANP组;C组,ANP加机械通气;观察时间均2h,连续观察平均动脉压(MAP)、SpO2、体温变化和血气分析,并保持动脉血PaCO2在35～45mmHg。实验开始即刻和实验结束时(除对照组外)抽取动脉血,处死大鼠后取肺叶组织观察肺组织病理和肺湿/干重比值;进行支气管肺泡灌洗液(BALF)提取,分析BALF中细胞变化,检测BALF中巨噬细胞炎性蛋白-2(MIP-2)和TNF-α浓度水平。结果 HE染色切片B、C两组均出现明显病理性改变,B组和C组肺湿/干重比值大于A组(P<0.05);B组和C组比较无明显变化;C组细胞聚集数较A组和B组明显(P<0.05)。各组BALF和血清炎性细胞因子比较,BALF和血清中MIP-2水平C组高于其他两组,C组与B组比较有统计学差异(P<0.05);各组TNF-α水平比较,BALF和血清中B组和C组高于A组,B组与C组BALF中TNF-α水平比较有统计学差异(P<0.05)。结论小潮气量机械通气对已存病理性肺组织的影响主要表现在局部或血液循环内致炎性细胞因子和(或)化学介质释放的增加,而对肺泡组织结构和形态学无明显影响。

Objective To investigate the effects of mechanical ventilation on lung tissue pathology and proinflammatory cytokines responses in acute pancreatitis rats.MethodsForty-five Sprague-Dawley were catheterized jugular arteria and femoral vein,and a tracheostomy was performed 48 h after intraperitoneal injection with L-arginine.The randomly enrollment of rats was stratified according to three intervention treat groups:group A(control group),48 h after intraperitoneal injection with normal saline;group B,acute pancreatitis;group C,acute pancreatitis plus mechanical ventilation(VT 8 ml/kg,RR 60 bpm).Mean artery pressure,SpO2,temperature and blood air analysis were performed during experiment;bronchoalveolar lavage fluid(BALF),blood sample and tissue slice was performed,and then histopathologic change was tested from harvested tissue of the both lung and pancreas,macrophage and immunity cell were counted in blood sample by optical microscope;proinflammatory cytokines MIP-2 and TNF-α were measured in both the blood plasm and BALF by enzyme-linked immunoassay.ResultsA significant pathological changes were observed in both group B and group C;lung wet-to-dry weight ratio of group B and group C was greater than group A(P<0.05);cells aggregation of group C was higher than group A and group B.The level of MIP-2 in group B and group C significantly increased compared with those in control group(group A)(P<0.05),and the level of MIP-2 in BALF was significantly different in group B compared with group C(P<0.05);the level of MIP-2 of blood plasm of group C was higher than other groups(P<0.05).The level of TNF-α of BALF in group B and group C were significantly higher than that in group A(P<0.05),and the level of TNF-α of blood plasm in group A,B and C present in order heighten.ConclusionsArginine-induced and mechanical ventilation can cause pathologic injury of pulmonary in a difference degree;and different change of various cytokines are primed by L-arginine in the systemic circulation and are further activated by mechanical ventilation in the pulmonary circulation.