硫化氢急性中毒大鼠肺组织细胞因子和核因子κB的改变及乌司他丁的影响

Effect of ulinastatin on cytokines and NF-K B expression in lung tissue of acute HzS-intoxicated rats

目的探讨硫化氢（H墨）急性中毒大鼠肺组织TNF-α、IL-6、IL-10及核因子14B（NF-KB）的动态变化及乌司他丁（UTl）对其的影响。方法将96只清洁级SD大鼠随机分为正常对照组（NS组，n=8）．UTI对照组（UTI组，n=8），H2s染毒模型组（H2s组，n=40）和UTI干预组（H2S＋UTI组，n=40），分别予以空气、H2s及UTI。建模后在不同时点处死后采用ELISA法和RT-PCR法测定肺组织中IL-6、IL-10、TNF—α的水平和mRNA表达变化：RT—PCR法和Westernblot法检测肺组织NF-KBmRNA和蛋白的表达；并观察肺组织病理学改变。结果与NS组比较，2、6、12、24、48hH2s组大鼠肺组织TNF-OC、IL-6、IL-10水平和mRNA表达以及NF—KBmRNA和蛋白表达均明显升高（均P〈0．01）；与H2s组比较。H2s＋UTI组2、6、12、24、48hTNF-α、IL-6水平和mRNA表达以及NF—KBmRNA和蛋白表达均明显降低（P〈0．05或O．01）。IL-10水平和mRNA表达明显升高（均P〈0．01）。光镜下见H2S组在染毒后24h肺组织损害明显，H2S＋UTI组肺损伤有所减轻。结论H2S吸入性中毒可致急性肺损伤，早期肺组织中NF-KB表达增加，细胞因子TNF-α、IL-6及IL-10水平升高，而UTI干预能显著降低NF-KB表达及TNF-α、IL-6水平，提高抗炎因子IL-10水平，减轻肺损伤。

Objective To investigate the effect of ulinastratin （UTI） on tumor necrosis factor- α （TNF- α ）, interleukin-6 （IL-6）, interleukin-10 （IL-10） and nuclear factor K B （NF- K B ） in lung tissue of acute HzS-intoxicated rats. Methods A total of 96 SD rats of clean grade were divided randomly into 4 groups： normal control group（NC group, n=8）, UTI control group （UTI group, n=8）, H2S-intoxicated model group（ H2S group, n=40） and UTI treatment group（H2S＋UTI group, n=40）.They were respec- tively assigned to receive air, HzS or UTI. After modeling, the levels and mRNA expression of TNF- α, IL-6 and IL-10 in the lung tissue were measured by ELISA and RT-PCR methods, and the expression of NF- K B mRNA and protein in the lung tissue wasdetected by RT-PCR and Western blot methods. Pathological changes of lung tissue were observed by light microscopy. Re- sults The pulmonary TNF- α, IL-6 and IL-10 levels and mRNA expression, and NF- K B mRNA and protein expression at 2, 6, 12, 24 and 48h（P〈0.01） in H2S group were markedly increased compared with those in NC group. In comparison with H2S group, the pulmonary TNF-α, IL-6 levels and mRNA expression, and NF-K B mRNA and protein expression at 2, 6, 12, 24 and 48h in H2S＋UTI group were decreased（P〈0.05or0.01）, and the IL-10 levels and mRNA expression were increased （P〈 0.01）. At 24h after modeling, histopathology showed that the degree of lung damage was also attenuated in H2S＋UTI group. Conclusion The levels and mRNA expressions of TNF-α, IL-6, IL-10 and NF-κB are up-regulated markedly in acute lung injury induced by HzS inhalation. UTI can inhibit the levels of NF- K B, TNF-α and IL-6, and up-regulate the level of IL-10 and reduce lung injury.