过度机械通气所致大鼠肺组织损伤时蛋白酶激活受体-2的表达

目的观察不同时间点大潮气量机械通气大鼠肺组织中蛋白酶激活受体-2（PAR-2）的表达,以探讨过度机械通气所致肺损伤与肺组织PAR-2水平的关系。方法 42只健康雄性SD大鼠随机分为对照组（Ad组）、小潮气量组（Ld组）、大潮气量组（H组）,H组在0.5h、1h、2h和3h四个时间点再分为a、b、c、d四个亚组,各组大鼠均为7只。机械通气组中每只大鼠采用经环甲膜切开气管插管。在相应时间点用窒息法将大鼠处死,取肺组织在光镜下观察病理改变,并分别以RT-PCR、免疫组化法检测肺组织PAR-2的mRNA和蛋白表达,并以SPSS 17.0统计软件分析结果。结果与Ad组和Ld组相比,H组大鼠肺组织损伤评分明显升高（P〈0.05）。PAR-2mRNA检测结果,PAR-2/β-actin在Ad组几乎不表达,Ld组可有极少量表达,H组表达明显,各组间差异有显著性（P〈0.05）。PAR-2mRNA蛋白检测结果,通过图像分析系统比较各组的光密度,显示各组间差异有显著性（P〈0.05）。后两种检测以Hd组变化最明显,差异有统计学意义（P〈0.05）。结论大潮气量机械通气可导致正常大鼠肺组织PAR-2mRNA和蛋白表达水平增强,可能在机械通气相关性肺损伤的发生发展过程中起重要作用。

Expression of protease-activated receptor-2 in lung injury of rats with hyperventilation

Objective To observe the expression of protease-activated receptor-2(PAR-2) in experimental rat ventilator-induced lung injury with high-volume mechanical ventilation at different time,investigate the relationship between the expression of PAR-2 and ventilator-induced lung injury.Methods Total of 42 Sprague-Dawley rats were randomly divided into a control group(group Ad,n=7),a normal tidal volume(VT) group(group Ld,n=7),and a hyperventilation group of relative larger VT group(group H,n=28).Rats in group H were randomly divided into 4 subgroups respectively by 0.5,1,2 and 3 h.Rats were inserted tracheal catheter via cricothyroid membrane under urethane injection anesthesia.Rats received different volume of ventilation except the control group.The samples of lung were collected after ventilation.Lung tissue histopathological changes were observed.The mRNA expression and the protein expression of PAR-2 in lungs were detected by RT-PCR and immunohistochemistry at each time point.Results High-volume mechanical ventilation resulted in substantial lung morphological changes.The interstitial pulmonary edema and pneumorrhagia were significantly higher in group H than in the control group and normal tidal volume group(P<0.05).In group A there were no PAR-2 mRNA(PAR-2/β-actin) expression,in group L there were small amounts of PAR-2 mRNA exprssion,and PAR-2 mRNA expression increased significantly in group H and it maintained a higher level since then,especially at 3h after ventilation(P<0.05).The changing trend of the expression of PAR-2 protein was the same as that of PAR-2 mRNA expression.Conclusion The expression of PAR-2 mRNA and PAR-2 protein increase significantly with high-volume mechanical ventilation,and it may play an important role in VILI.