硫糖铝对百草枯中毒大鼠细胞因子的影响

Effect of sucralfate on cytokines in rat with paraquat poisoning

目的 探讨硫糖铝干预治疗对百草枯（PQ）中毒大鼠细胞因子的影响。方法 健康雄性SD大鼠72只，按随机数字表法分为PQ模型组、碳酸氢钠干预组（SB组）和硫糖铝混悬凝胶干预组（LTL组），每组24只。采用一次性灌胃PQ溶液25 mg/kg制备PQ中毒大鼠模型。SB组和LTL组分别于染毒后2 h内灌胃100 g/L碳酸氢钠或200 g/L硫糖铝混悬凝胶5 mL·kg-1·d-1；PQ模型组灌胃等量无菌生理盐水。各组分别于染毒后1、3、6、10 d采集大鼠腹主动脉血，采用酶联免疫吸附试验（ELISA）测定血清肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）及转化生长因子-β1（TGF-β1）水平；取大鼠左肺组织，测定肺湿/干重（W/D）比值。结果 随染毒时间延长，各组肺W/D比值均逐渐升高，10 d达峰值；但SB组和LTL组肺W/D比值升高幅度明显减小，6 d和10 d均较PQ模型组显著降低（SB组与PQ模型组：6 d为4.99±0.79比6.98±0.86，10 d为5.61±0.36比7.36±0.95；LTL组与PQ模型组：6 d为4.61±0.24比6.98±0.86，10 d为4.24±0.20比7.36±0.95，均P〈0.05），而SB组与LTL组比较差异无统计学意义（均P〉0.05）。PQ染毒后，3组血清TNF-α、IL-10和TGF-β1水平均升高，3 d达峰值后逐渐下降；与PQ模型组比较，SB组和LTL组血清TNF-α、IL-10和TGF-β1水平均明显降低〔SB组与PQ模型组：3 d TNF-α（ng/L）为147.6±12.3比168.2±11.3，3 d IL-10（ng/L）为65.4±3.2比115.1±9.2，3 d TGF-β1（ng/L）为356.3±50.3比415.6±68.3；LTL组与PQ模型组：3 d TNF-α（ng/L）为82.2±7.4比168.2±11.3，3 d IL-10（ng/L）为44.4±5.2比115.1±9.2，3 d TGF-β1（ng/L）为296.3±40.2比415.6±68.3，均P〈0.05〕，以LTL组降低更为显著（均P〈0.05）。结论 PQ中毒早期使用硫糖铝进行胃肠灌洗能有效减少肺组织炎性渗出，抑制细胞因子分泌。

Objective To explore the effect of sucralfate on cytokines in rats with paraquat （PQ） poisoning.Methods Seventy-two healthy male Sprague-Dawley （SD） rats were randomly divided into PQ model group, sodium bicarbonate intervention group （SB group） and sucralfate suspension gel group （LTL group）, with 24 rats in each group. The rat model of PQ poisoning was reproduced by one-time intragastric administration of PQ solution 25 mg/kg. The rats in SB group and LTL group were intragastricly administrated with 5 mL·kg-1·d-1 of 100 g/L sodium bicarbonate or 200 g/L sucralfate at 2 hours after exposing to PQ, and the rats in PQ model group were given the same amount of sterile saline. The abdominal aortic blood of rats was collected at 1, 3, 6, and 10 days after PQ poisoning, and the levels of serum tumor necrosis factor-α （TNF-α）, interleukin-10 （IL-10） and transforming growth factor-β1 （TGF-β1） were determined by enzyme-linked immunosorbent assay （ELISA）. The left lung tissue was harvested, and lung wet/dry weight （W/D） ratio was assessed.Results With prolonged exposure, lung W/D ratios in all the groups were increased gradually, reached the peak at 10 days, but in the SB group and LTL group, the amplitude of increase was obviously reduced, the ratios were significantly decreased at 6 days and 10 days as compared with those in PQ model group （SB group vs. PQ model group： 4.99±0.79 vs. 6.98±0.86 at 6 days, 5.61±0.36 vs. 7.36±0.95 at 10 days; LTL group vs. PQ model group： 4.61±0.24 vs. 6.98±0.86 at 6 days, 4.24±0.20 vs. 7.36±0.95 at 10 days, all P 〈 0.05）, but there was no significant difference between SB group and LTL group （all P 〉 0.05）. After PQ poisoning, the levels of TNF-α, IL-10 and TGF-β1 were elevated, and reached the peak at 3 days and then decreased gradually. Compared with the PQ model group, serum TNF-α, IL-10 and TGF-β1 levels in SB group and LTL group were decreased significantly [SB group vs. PQ model group： 3-day TNF-α （ng/L） was 147.6±12.3 vs. 168.2±11.3, 3-day IL-10 （ng/L） was 65.4±3.2 vs. 115.1±9.2, 3-day TGF-β1 （ng/L） was 356.3±50.3 vs. 415.6±68.3; LTL group vs. PQ model group： 3-day TNF-α （ng/L） was 82.2±7.4 vs. 168.2±11.3, 3-day IL-10 （ng/L） was 44.4±5.2 vs. 115.1±9.2, 3-day TGF-β1 （ng/L） was 296.3±40.2 vs. 415.6±68.3, all P 〈 0.05], especially in LTL group （all P 〈 0.05）.Conclusion Early gastrointestinal lavage with sucralfate could effectively reduce the inflammatory exudation in lung tissue after PQ poisoning, and inhibit the cytokine secretion.