核转录因子kB在大鼠肺纤维化中的表达及白藜芦醇干预作用

目的观察核转录因子kB（NF-kB）在博莱霉素致大鼠肺纤维化中的表达及白藜芦醇（Res）干预作用。方法90只雌性SD大鼠随机分为对照组、模型组、Res低（25mg／kg）、中（50mg／kg）、高（100mg／kg）剂量组及地塞米松（DM，3mg／kg）干预组，以气管内注入博莱霉素法制备肺纤维化大鼠模型，观察各组肺组织炎症及纤维化的改变情况，检测各组肺组织羟脯氨酸含量，并用免疫组织化学方法测定肺组织中NF-kB蛋白的表达水平。结果①在实验性大鼠肺纤维化发病过程中，呈现典型的肺泡炎（7d）、纤维组织增生（14d）及稳定的肺纤维化（28d）等表现。②与对照组[（265．20±8．90）ug／g，（325．60±31．26）ug／g，（325．80±48．75）ug／g]相比，第7、14、28天模型组[（486．00±36．15）ug／g，（770．60±63．29）ug／g，（1065．00±181．31）ug／g]及Res低剂量组[（454．80±46．61）ug／g，（803．20±126．96）ug／g，（962．00±184．12）ug／g3中羟脯氨酸含量随纤维化进展逐渐增高（P值均〈0．05），Res高[（363．80±27．31）ug／g，（511．40±43．62）ug／g，（530．20±161．04）ug／g]、中剂量组[（376．60±30．15）ug／g，（510．00±76．66）ug／g，（596．40±139．00）ug／g]及DM干预组[（349．60±41．53）ug／g，（475．60±38．64）ug／g，（524．80±135．89）ug／g]变化趋势与模型组及Res低剂量组类似，但羟脯氨酸含量低于同时间点的模型组及Res低剂量组（P值均〈0．05）。③第7、14、28天模型组（28．02±1．36，42．22±1．29，54．33±0．58）及Res低剂量组（27．61±1．28，42．16±0．99，53．86±0．76）中NF—kB表达水平高于对照组（2．89±0．19，3．01±0．33，2．90±0．28，P值均〈0．05），并呈现逐渐增高的趋势，Res高（23．04±1．46，27．80±1．48，33．92±0．96）、中剂量组（23．67±0．59，28．38±0．64，34．28±1．08）及DM干预组（22．14±2．14，27．22±1．89，33．18±1．44）变化趋势与模型组类似，但表达水平均低于同时间点的模型组及Res低剂量组（P值均〈0．05）。结论NF-kB的高表达在肺纤维化的发病机制中起重要作用，Res抑制NF-kB的高表达可能是其防治肺纤维化的机制之一。

Expression of nuclear factor-kB and intervention of resveratrol in rats with pulmonary fibrosis

Objective To observe the effect of resveratrol on bleomycin-indueed pulmonary fibrosis in rats and the expression of nuclear factor-kB （NF-kB）. Methods 90 female SD rats were randomly divided into control group, model group, low （25 mg/kg）,middle （50 mg/kg）, and high （100 mg/kg） resveratrol treated group, dexamethasone （3 mg/kg）-treated group. Rats with pulmonary fibrosis were reproduced by intratracheal injection of bleomycin. The changes of inflammation and fibrosis in lung tissues of all groups were observed. The content of hydroxyproline in lung tissues was detected. The expression of NF-kB protein in lung tissue was determined by immunohistoehemistry. Results （1）In the pathogenesis of pulmonary fibrosis in the experimental rats, there was showing the typical alveolitis （7 d）, fibrous tissue hyperplasia （14 d）, stable pulmonary fibrosis （28 d）, and other performances. （2） Compared with the control group [（265.20±8.90） ug/g,（325. 60±31. 26） ug/g,（325. 80±48. 75） ug/g], the content of hydroxyproline increased with the progression of fibrosis in the model group [（486.00±36.15） ug/g, （770. 60± 63. 29） ug/g,（1 065.00±181.31） ug/g ]and low resveratrol-treated group [（454.80±46. 610） ug/g,（803.20± 126.96） ug/g,（962.00±184.12） ug/g ]on the 7th,14th,and 28th day. The content of hydroxyproline in the middle [（376.60±30.15） ug/g, （510.00± 76.66） ug/g, （ 596.40± 139.00） ug/g] and high resveratrol-treated group [（363.80±27. 31） ug/g, （511.40±43.62） ug/g, （530.20 ± 161.04） ug/g] and the dexamethasone-treated group [（349.60 ± 41.53） ug/g, （475.60±38.64） ug/g,（524.80±135.89） ug/g] had the same trends with that in the model group and the low resveratrol-treated, but was less than them （allP 〈0.05）. （3）The expression of NF-kB protein on the 7th, 14th, and 28th day in the model group（28.02± 1.36,42.22±1.29,54.33±0.58） and low resveratrol-treated group（27.61±1.28,42.16±0. 99,53.86±0.76） was higher than that in the control group （2.89±0.19,3.01 ±0.33,2.90±0.28,all P 〈0.05）, and showed the trend of gradually increasing. The middle （23.67 ± 0. 59, 28. 38±0. 64, 34.28 ± 1.08） and high resveratrol-treated group （23.04 ± 1.46, 27.80 ± 1.48, 33.92±0.96） and the dexamethasone treated group（22.14 ± 2.14, 27.22 ±1.89,33.18 ±1.44）had the same trends with the model group and the low resveralrol-treated group, but lower than them （all P 〈0.05）. Conclusions High expression of NF-kB plays an important role in the pathogenesis of pulmonary fibrosis. Resveratrol can inhibit the expression of NF-kB, which may be one of the mechanisms of prevention and treatment of lung fibrosis.