烟酸对博莱霉素肺纤维化大鼠的干预影响

The effect of niacin in the bleomycin rat model of lung fibrosis

目的研究烟酸对博莱霉素肺纤维化大鼠模型的干预影响以及可能的机制。方法54只清洁级SD大鼠随机分为3组:烟酸组(N组),模型组(B组),正常组(CN组)。烟酸组和模型组大鼠实验当天气管内滴入博莱霉素5 mg/kg,正常组气管内滴入等量生理盐水。在气管内滴药后第7,14,28天每组各处死6只动物,取肺组织称重计算肺系数,行HE、M asson染色并做肺泡炎、肺纤维化评分,比色法测羟脯氨酸含量,免疫组化法测转化生长因子-β1(TGF-β1),α-平滑肌肌动蛋白(α-SMA)水平表达。结果模型组TGF-β1,α-SMA蛋白表达明显高于正常组,烟酸组则低于模型组。模型组各时间点肺泡炎评分均高于同一时间点正常组和烟酸组;实验第14,28天肺纤维化程度,肺系数,羟脯氨酸含量也高于同期正常组及烟酸组。结论烟酸可以抑制博莱霉素肺纤维化的形成,可能与部分抑制肺组织TGF-β1,α-SMA蛋白表达有关。

Objective To study the effect of niacin on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism. Methods Fifty four Spragne-Dauley rats were randomly divided into three groups： the niacin group（N） ,the model group（B） and the control group（CN）. The niacin group was fed with a diet containing 2. 5% niacin three days before intratracheal instillation and throughout the experiment, other groups were fed with a control normal diet. Rats were intratraeheally instilled with bleomycin in the niacin and model groups and with saline in the control group. Six animals in each group were sacrificed on day 7, 14, and 28 after the intratraeheal instillation. Hydroxyproline concentrations and lung index were determined. Histological changes of the lungs were evaluated by HE staining and Masson＇s trichrome staining,according to which the degree of alveoliti and pulmonary fibrosis were graded. The expressions of transforming growth factor-betal （TGF-β1 ） and alpha-smooth muscle actin（ α-SMA ）protein in lungs were assessed by immunohistochemistry. Result The expressions of TGF-β1 and α-SMA were elevated in the model group compared with the control group and the niacin group. Alveoliti points in the model group were increased compared with other groups at all time points. Pulmonary fibrosis markers, lung indexes and hydroxyproline concentrations of the model group were higher than those of other groups. Conclusion Niacin alleviates bleomycin-indueed pulmonary fibrosis in rats, probably through partial inhibition of the α-SMA and TGF-β1 expressions in lung tissues.