丙泊酚对大鼠机械通气相关肺损伤的保护作用及机制

目的 探讨丙泊酚对大鼠机械通气相关肺损伤影响的作用机制.方法 24只Wistar清洁级大鼠随机分为3组(n=8),采用压力控制机械通气模式通气4 h.A组为模型组,通气模式为吸气峰压(PIP)=25 cm H2O(1 cm H2O=0.098 kPa),呼气末正压(PEEP)=2 cm H2O;B、c组为同时输注丙泊酚组,通气模式同A组,B组输注模式为静注2mg/kg,继以4mg·kg-1·h-1速度持续输注;C组输注模式为5 mg/kg,继以10 mg·kg-1·h-1速度持续输注,记录基础时点、1、2、3、4 h的MAP、HR和动脉血气.4 h后处死全部大鼠,测量肺组织湿/干比(W/D),支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中总蛋白、肿瘤坏死因子α(tumor necrosis factora,TNF-α)、白介素1β(interleukin1β,IL-1β)、白介素6(interleukin6,IL-6)、白介素10(interleukin10,IL-10)和巨噬细胞炎性蛋白2(macrophage inflammatorv protein2,MIP-2)的含量,肺组织匀浆中丙二醛(malondialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)的含量,观察肺组织病理形态学变化.结果 A组MAP和PaO2在4 h时显著降低,由(116.0±7.4)mm Hg(1 mm Hg=0.133 kPa)和(379±65)mm Hg降低到(73±21)mm Hg和(103±48)mm Hg,与基础值相比差异有统计学意义(P<0.05),而B、C组与基础值相比差异无统计学意义.在4 h时A组的PaCO2显著升高(P<0.05),而B、C两组与基础值相比差异无统计学意义.肺组织湿/干比、BALF中总蛋白含量、TNF-α和MIP-2浓度A组明显高于B、C组(P<0.05),肺组织匀浆巾MDA浓度A组明显高于B、C组(P<0.05),A组SOD浓度也有所降低,但和B、C组差异无统计学意义.肺组织学病理评分B、C组也好于A组(P<0.05),B、C组间差异无统计学意义.结论 丙泊酚可减轻大鼠机械通气相关肺损伤,其机制可能与其减少炎症因子的释放,减少中性粒细胞在肺内的积聚,抑制过氧化损伤有关.

The protection effects of propofol on ventilator-induced lung injury in rats

Objective To investigate the mechanisms of propofol on ventilator-induced lung injury in rats produced by high PIP ventilation. Methods Twenty-four anesthetized Wistar rats weighting 280 g-320 g were randomly divided into tlhree groups (n=8). Rats were ventilated with high PIP pattern (PIP=25 cm H2O,PEEP=2 cm H2O) for 4 h. Propofol was given in a bolus of 2 mg/kg (group B) or 5 mg/kg (group C), followed by continuous infusion with 4 mg·kg-1·h-1 (group B)or 10 mg·kg-1·h-1(group C). No Propofol was given for group A. MAP, HR were recorded and arterial blood gases were analyzed. Lung wet and dry weight ratio( W/D), tumor necrosis factora(TNF-α), interleukin1β(IL-1β), IL-6, IL-10, macrophage inflammatory protein2(MIP-2) and protein content in bronchoalveolar lavage fluid (BALF) , content of malondialdehyde (MDA) and superoxide dismutase (SOD) in lung homogenate were determined.Pathological change of lung was examined and lung injury was scored as well. Results MAP and PaO2 decreased from (116±7.4) mm Hg and (379±65) mm Hg to (73±21 )mm Hg and (103±48)mm Hg, and PaCO2 increased at fourth hour in group A(P<0.05). PaO2 in group B and C were higher than in group A after 3 h(P<0.05). Lung W/D weight ratio, TNF-α, MIP-2 and protein content in BALF were higher in group A (P<0.05), and MDA was higher in group A (P<0.05). No significant difference between group B and C. Pathological changes of lung in group B and C were all better than those in group A. Conclusion Propofol may attenuate VILI in rats partly by reducing the release of cytokine, decreasing the accumulation of neutrophil in the lung, and inhibiting peroxidized injury.