孟鲁司特对百草枯所致大鼠肺损伤的治疗作用

Empirical study of therapeutic effect of montelukast on acute lung injury induced by paraquat in rats

目的探讨孟鲁司特对百草枯（PQ）中毒所致大鼠肺组织中丙二醛（MDA）、超氧化物歧化酶（SOD）、肺湿／干质量比（W／D）和血清中肿瘤坏死因子（TNF-α）、白细胞介素-10（IL-10）、肺组织中核因子KB（NF-κBp65）及肺组织病理变化的影响。方法取SD大鼠104只，随机（随机数字法）分为3组，PQ组40只、孟鲁司特组40只、对照组24只。PQ组和孟鲁司特组用百草枯一次性染毒，分别在不同处理后第1、3、5、7天时处死大鼠。观察肺组织中MDA和SOD含量、肺湿／干质量比（W／D）、血清TNF-α、IL-10含量及肺组织中NF-κB065含量，并取肺组织制备标本分别在光镜和电镜下观察肺组织的病理改变。结果PQ组第7天时肺组织中MDA含量、肺组织湿／干质量比、血清TNF-α和IL-10含量、肺组织中NF-κBp65含量明显高于对照组，SOD含量明显低于对照组，差异均具有统计学意义（P〈0．01）。孟鲁司特组第7天时肺组织中MDA含量、肺组织湿／干质量比、血清TNF-α和IL-10含量、肺组织中NF-κBp65含量明显低于PQ组，SOD含量明显高于PQ组，差异均具有统计学意义（P〈0．05）。光镜及电镜观察PQ组病理学改变为急性弥漫性肺损伤，表现为肺泡腔内出血、渗出、炎性细胞浸润，I型和Ⅱ型上皮细胞坏死脱落；孟鲁司特组大鼠肺组织病理改变为局灶性肺泡少量炎性细胞浸润，I型上皮细胞完整，Ⅱ型上皮细胞未见明显坏死。结论孟鲁司特对百草枯中毒所致大鼠急性肺损伤具有一定的保护作用。

Objective To discuss the effect of Montelukast （Mont） on MDA, SOD, W/D, TNF-α, IL-10 and NF-κBp65 in lung tissue of Wistar rats poisoned by paraquat （PQ） and also to observe the pathological changes of the lung tissue. Methods A total of 104 Wistar rats were divided into 3 groups in random （random number）, namely PQ group （n =40）, Mont group （n =40） and control group （n =24）. PQ （20 mg,/kg） was administered by intra-peritoneal route to rats of PQ group and Mont group and narcotics were used for 2 hours. Mont in dose of 50 mg/kg was administered intra-gastrically to rats of Mont group per day and saline instead were administered to PQ group and control group per day until they were sacrificed for experiment. Of both PQ group and Morn group, 10 rats were sacrificed at each interval of 1, 3, 5 and 7 daysrespectively after modeling, whereas 6 rats of control group were sacrificed at each interval. The levels of MDA and SOD in lung tissue and W/D of lung tissue, the levels of serum TNF-α and IL-10 and the level of NF- κBp65 in lung tissue were determined. Further, the specimen of lung tissue was prepared for electron microscopy observation. Results The level of MDA in lung tissue of PQ group was （8. 19±0. 53） nmol/mg prot, which was significantly higher than that of control group on the 7th day. The level of SOD in lung tissue of PQ group was （ 128.76±10. 18） U/mg prot, which was significantly lower than that of control group. In PQ group, the W/D of lung tissue （ 6. 62 ±0. 42）, level of serum TNF-α （ 156. 16 ± 11.13 ） pg/ml, level of IL-10 （43.63±4. 44） pg/ml and level of NF-κBp65 in lung tissue （0. 23±0. 02） were significantly higher than those in control group （P 〈0. 01 ）. In Mont group on the 7th day, the level of serum TNF-α （ 129. 99 ± 13. 13） pg/ml, level of serum IL-10 （34. 28 ± 3. 80） pg/ml and level of NF-KBp65 in lung tissue （0. 20 ± 0. 02） were significantly lower than those in PQ group （P 〈0. 01 ）. In the PQ group, pathological changes of lung tissue under the light and electron microscopes were acute diffused lung injury manifested itself in hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space, and the necrosis and defluxion of I type and lI type epithelia cells. The pathological changes in Mont group were localized with infiltration of scanty inflammatory cells, and I type epithelia cells were intact and there was no obvious necrosis of U type epithelia cells. Conclusions Mont has protective effects on acute lung injury caused by PQ poisoning in rats.