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目的:本研究探讨不同剂量他克莫司(FK506)对百草枯(PQ)中毒致大鼠急性肺损伤(ALI)炎症反应的作用,为治疗PQ致ALI提供新方法。方法:75只SPF级8周龄SD雄性大鼠,随机分为5组(每组各15只):正常对照组(C组)、PQ中毒组(PQ组)、FK506低剂量组(PT1组)、FK506中剂量组(PT2组)和FK506高剂量组(PT3组)。以一次性腹腔内注射30mg/kg的PQ溶液或等量无菌生理盐水复制PQ中毒ALI模型组和C组。每间隔24h,PT1、PT2、PT3组分别按照2、4、8mg/kg的FK506溶液剂量灌胃,C组在同一时间点给予等量生理盐水灌胃,造模后6、12、24、48、72h分批处死大鼠。观察各组大鼠一般情况、肺组织外观;取肺组织行苏木精-伊红染色并病理评分;检测支气管肺泡灌洗液(BALF)中性粒细胞(PMN)数量;测定肺组织匀浆中髓过氧化物酶(MPO)、肿瘤坏死因子-α(TNF-α)浓度;最后分析上述各项指标与肺组织病理评分的相关性。结果:(1)与C组比较,PQ组病理损伤最重,病理评分最高;对应时间点的PT1、PT2、PT3组病理损伤程度低于PQ组,肺组织病理学评分均低于PQ组,3组间两两比较差异无统计学意义。(2)与C组比较,PQ、PT1、PT2、PT3组在PQ中毒6h后,BALF中PMN数量,肺组织匀浆中MPO、TNF-α含量逐渐增加,均在72h时升至最高,组间比较差异有统计学意义(P<0.05);与PQ组相比,各对应时间点,PT1、PT2、PT3组的PMN数量减少,MPO、TNF-α含量降低(P<0.05);但3组间两两比较差异无统计学意义;(3)各时间点的肺组织病理损伤评分与PMN数量及TNF-α含量具有正相关性(P<0.05),相关系数分别为0.881、0.808。结论:FK506能在一定程度上减轻PQ致大鼠ALI,主要表现在PMN数量减少,炎症反应程度减轻。
OBJECTIVE: The purpose of this study was to investigate the effects of different doses of FK506 on the inflammation of acute lung injury (ALI) induced by paraquat (PQ) poisoning in rats and to provide a new method for the treatment of PQ-induced ALI. Methods: Seventy-five SD male SD rats of 8 weeks old with SPF were randomly divided into 5 groups (15 rats in each group): normal control group (C group), PQ poisoning group (PQ group), FK506 low dose group ), FK506 medium dose group (PT2 group) and FK506 high dose group (PT3 group). One-time intraperitoneal injection of 30mg / kg PQ solution or an equal volume of sterile saline replication PQ poisoning ALI model group and C group. Each interval 24h, PT1, PT2, PT3 group were treated with 2,4,8mg / kg FK506 solution dose, group C at the same time point given the same amount of saline gavage, modeling 6,12,24,48 The rats were killed in batches in 72h. The general condition of the rats in each group and the appearance of the lung tissue were observed. The lung tissue was stained with hematoxylin-eosin and pathological score. The number of neutrophil (PMN) in bronchoalveolar lavage fluid (BALF) (MPO) and tumor necrosis factor-α (TNF-α) levels were analyzed. The correlation between the above indexes and pathological scores of lung tissue were analyzed. Results: (1) Compared with group C, PQ group had the highest pathological damage and the highest pathological score. The pathological changes of PT1, PT2 and PT3 group were lower than those of PQ group at the corresponding time points, There was no significant difference between the two groups in any of the three groups. (2) Compared with group C, the number of PMN and the contents of MPO and TNF-α in BALF increased gradually in PQ, PT1, PT2 and PT3 groups at 6h after PQ poisoning, Compared with PQ group, the number of PMN and the content of MPO and TNF-α in PT1, PT2 and PT3 groups decreased (P <0.05) compared with those in PQ group (P <0.05), but the difference was statistically significant (3) There was a positive correlation between the number of PMN and the level of TNF-α (P <0.05) at all time points, and the correlation coefficients were 0.881,0.808. Conclusion: FK506 can alleviate the PQ-induced ALI in rats to a certain extent, mainly in the reduction of the number of PMN and the reduction of inflammatory reaction.