急性百草枯中毒大鼠肺组织Toll样受体4和核因子-κB表达的变化

Expressions of toll-like receptor 4 mRNA and nuclear factor-kB mRNA in lung tissue of rats with acute paraquat poisoning

目的观察急性百草枯（PQ）中毒大鼠肺组织中Toll样受体4（TLR4）和核因子．κB（NF-kB）mRNA表达的变化，探讨TLR4-NF-kB通路在急性PQ中毒肺损伤中的作用。方法30只雄性sD大鼠随机分为2组：生理盐水（NS）对照组（6只，NS腹腔注射），PQ染毒组（24只，腹腔注射PQ溶液，20mg／kg）。PQ染毒组分别在染毒后6、24、48h及72h麻醉处死，Ns对照组于处理后6h处死，进行肺组织HE染色，病理学观察，用实时定量PCR方法检测TLR4和NF-kB的mRNA表达情况，用ELISA方法测定肺组织中肿瘤坏死因子-α（TNF-α）、血清中IL-6含量。结果PQ染毒组大鼠肺组织病理表现为早期充血水肿明显，大量炎性细胞浸润。与NS对照组相比PQ染毒组肺组织中TLR4和NF．kBmRNA的表达量、TNF-α、IL-6含量在各时间点均有不同程度升高，差异均具有统计学意义（P〈0．01）。结论大鼠急性PQ中毒后肺组织中TLR4和NF．κBmRNA表达量、TNF-α、IL-6含量明显上调，TLR4-NF-kB通路参与了PQ中毒大鼠肺损伤的早期病理生理过程。

Objective To investigate the expressions of toll-like receptor 4 mRNA and nuclear factor-KB （TLR4-NF-κB） mRNA in lung tissue of rats with acute paraquat poisoning. Methods Thirty male SD rats were randomly divided into two groups, namely normal saline group （ NS group, n = 6） and the PQ groups （n = 24）. The rats of PQ group were administered with 20 mg/kg PQ by intraperitoneal injection to establish the models of PQ induced lung injury. The saline was administered once instead in normal saline group. The rats of PQ group were sacrificed separately at 6 h, 12 h, 24 h, 48 h and 72 hours after modeling, while at 6 hours the rats of normal saline group was sacrificed. The expressions of TLR4 mRNA, NF-κB mRNA, and the levels of tumor necrosis faetor-ct and interlenkin-6 in lung （serum） of rats were detected. Meanwhile, pathological changes of the lung tissue were examined under optical microscope. Results There were no histopathological changes such as alveolar edema, hemorrhage and inflammatory cell infiltration found in NS group other than in PQ group. At the 72 h, the expressions of TLR4 mRNA （9.61 ±0.21） , NF-KB mRNA （5.62 ±0.24） , and the levels of TNF-α （153.08±5.02） pg/ml, and interleukin-6 （230. 08 ± 10. 64） pg/mL in lung tissue of rats were significantly higher in PQ group than those in control group （ P 〈 0. 01 ）. Conclusions In rats after PQ poisoning, the expressions of TLR4 mRNA, NF-KB mRNA, and the levels of TNF-αand IL-6 were higher than those in normal rats, and the TLR4-NF-κB pathway could play an important role in lung injury of rats with PQ poisoning.