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目的:研究茶多酚(简称TP)对博莱霉素(bleomycin,BLM)所致肺纤维化动物模型的干预作用,并探讨其作用机制。方法:将昆明种小鼠随机分为假手术组、模型组、醋酸泼尼松组、TP(大、中、小剂量)组。经气管内1次性灌注BLM复制肺纤维化动物模型,造模后第2天起各给药组给予相应药物灌服给药,药物干预后第7,14,28天分别处死动物,观察肺系数、肺组织羟脯氨酸(HYP)、谷胱甘肽(GSH)含质量和总抗氧化能力(T-Aoc)的变化;取固定部位肺组织作病理切片观察其病理形态;免疫组织化学技术测定肺组织中α-平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)和I型胶原(Col-I)蛋白的表达。结果:TP可显著降低肺纤维化小鼠的肺系数、肺组织中HYP的质量,显著提高肺组织的T-Aoc和GSH质量(P<0.01,P<0.05);光镜观察显示,给予TP干预的小鼠的肺泡炎程度与肺纤维化程度明显减轻(P<0.01,P<0.05);免疫组织化学结果显示TP能显著抑制肺组织中α-SMA、TGF-β1和Col-I蛋白的表达(P<0.01,P<0.05)。结论:TP对博莱霉素所致小鼠肺纤维化具有一定的干预作用,其作用机制可能与下调TGF-β1蛋白的表达和抑制肺肌成纤维细胞的活化以及下调其下游靶基因Col-I蛋白,从而抑制细胞外基质的过度生成以及增加机体的抗氧化能力有关。
Objective: To study the intervention effect of tea polyphenols (TP) on animal model of pulmonary fibrosis induced by bleomycin (BLM) and its mechanism. Methods: Kunming mice were randomly divided into sham-operation group, model group, prednisone acetate group, TP group (large, medium and small dose). One-time intratracheal instillation of BLM was used to replicate pulmonary fibrosis in animal models. The rats in each group were administered with the corresponding drugs on the second day after model establishment. Animals were sacrificed on the 7th, 14th and 28th days after the drug intervention, respectively. (P <0.01), the content of hydroxyproline (HYP), glutathione (GSH) and the total antioxidant capacity (T-Aoc) in the lung tissue were observed. The histopathology of lung tissue was observed by histological section. The expression of α-smooth muscle actin (α-SMA), transforming growth factor β1 (TGF-β1) and collagen type I (Col-I) Results: TP could significantly reduce the lung coefficient of lung fibrosis, the quality of HYP in lung tissue, and significantly improve the quality of T-Aoc and GSH in lung tissue (P <0.01, P <0.05). The results of light microscopy showed that TP The degree of alveolitis and the degree of pulmonary fibrosis were significantly reduced in the intervention mice (P <0.01, P <0.05). Immunohistochemistry showed that TP could significantly inhibit the expression of α-SMA, TGF-β1 and Col-I (P <0.01, P <0.05). CONCLUSION: TP may interfere with bleomycin-induced pulmonary fibrosis in mice, and its mechanism may be related to down-regulating the expression of TGF-β1 and inhibiting the activation of lung myofibroblasts and down-regulating the expression of its downstream target gene Col- I protein, thereby inhibiting the excessive formation of extracellular matrix and increase the body’s antioxidant capacity.