血红素加氧酶-1重组乳酸乳球菌灌胃对内毒素诱导大鼠急性肺损伤的作用

Effects of Gavage with Recombinant Lactococcus Lactis Containing Heme Oxygenase-1 on Endotoxin-induced Acute Lung Injury in Rats

目的:利用基因工程原理合成携带血红素加氧酶-1(HO-1)基因的乳酸乳球菌,给正常大鼠灌胃后,观察其对内毒素诱导大鼠急性肺损伤的保护效应。方法:随机将30只健康清洁级SD大鼠分为对照组(LPS组,n=10)、携带HO-1的乳酸乳球菌灌胃组(HO组,n=10,LPS模型建立前24 h灌胃)、拮抗剂组[锌原卟啉(ZnPP)组,n=10,HO灌胃24 h后,LPS模型建立前1 h腹腔注射ZnPP 10μmol/kg];LPS模型建立后4 h取材,比较各组动物支气管灌洗液(BALF)中髓过氧化物酶(MPO)活性、中性粒细胞(PMN)计数、肺组织湿干重比(W/D)、肺组织MPO活性,并在光镜下观察肺组织病理学改变。结果:与LPS组比较,HO组BALF中MPO、PMN计数和肺组织W/D均降低(P<0.05),肺组织病理学损伤减轻;与HO组比较,ZnPP组BALF中MPO、PMN计数和肺组织W/D均升高(P<0.05),肺组织病理学损伤加重;ZnPP组与LPS组比较差异无统计学意义(P>0.05)。结论:预先给大鼠用携带HO-1基因的乳酸乳球菌灌胃,可对内毒素诱导急性肺损伤大鼠产生一定的保护作用。

Objective： To evaluate the effect of gavage with recombinant laetoeeceus lactis （L. Lactis） containing heme oxygenase - 1 （ HO - 1 ） gane on endotoxin - induced acute lung injury in rats. Methods ： Thirty healthy SD rats of cleansing degree were randomly divided into 3 groups with 10 in each, namely, control group （ LPS group）, HO group （tavaged with recombinant L. Lactis containing HO - 1 24 hours before LPS model building）, ZnPP group （intraperitoneal injected Znpp 10 μmol/kg 24 hours after lavaged with recombinant L. Lactis containing HO-1 and 1 hour before LPS model building）. The rats were killed 4 hours after LPS intravenous injection. The my-eloperosidase （MPO） activity and PMN count in bronehoalveolar lavage fluid （BALF）, as well as the wet to dry weight （W/D） ratio and MPO activity of lung tissue were determined. Pathological changes of lung tissue were examined by microscopic. Results ： Compared with LPS group, MPO activity and PMN count in BALF, W/D ratio of lung tissue in HO group were significantly decreased. Histopathologic damages to the lung in HO group were also reduced. Compared with HO group, MPO activity and PMN count in BALF, W/D ratio of lung tissue in ZnPP group were significantly increased. And Histopathologic damages to the lung were also increased. No significant differences in MPO activity, PMN count and W/D ratio were found between LPS group and ZnPP group. Conclusion： Gavage with recombinant L. Lactis containing HO - 1 gene has protective effects on endotoxin - induced acute lung injury in rats.