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目的观察在不同时期给予留兰香油对博莱霉素引起的小鼠肺纤维化病理改变及肺组织中肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶-9(MMP-9)、金属蛋白酶抑制剂-1(TIMP-1)及α-平滑肌肌动蛋白(α-SMA)表达的影响。方法 ICR小鼠一次性气道内滴入博莱霉素建立肺纤维化模型,实验动物分为留兰香油治疗组和预防组,分别于造模后第8天和第1天开始给予留兰香油灌胃3周和4周。每7 d记录小鼠体重、死亡率;肺组织切片行HE、Masson染色观察气道炎症及纤维化程度,并对病理图片进行形态学测量分析;测定肺组织中羟脯氨酸(hydroxyproline)、TNF-α、TGF-β1、MMP-9及TIMP-1含量;测定肺组织中α-SMA表达水平。结果留兰香油14、42、140 mg.kg-1预防组能明显减少组织纤维化区域,部分肺泡结构得以保留,肺泡间隔胶原沉积减少;留兰香油14和140 mg.kg-1预防组能够明显降低肺组织中羟脯氨酸、TGF-β1和MMP-9含量;留兰香油14、42、140 mg.kg-1预防组能够明显降低肺内α-SMA表达水平。留兰香油治疗组除14 mg.kg-1组明显减弱α-SMA表达外对其余各项指标均没有明显作用。结论早期给予留兰香油对博莱霉素引起的小鼠肺纤维化有减轻作用,其机制可能是通过降低肺组织中MMP-9及TGF-β1的含量,减少基底膜断裂,减少成纤维细胞增殖和转化,减少肌成纤维细胞α-SMA表达及细胞外基质的合成,对肺纤维化初期起到干预作用。
Objective To observe the effects of Spearmint oil on bleomycin-induced lung fibrosis and the changes of tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) (MMP-9), metalloproteinase-1 (TIMP-1) and alpha-smooth muscle actin (α-SMA) expression. Methods ICR mice were infused with bleomycin through the airway to establish pulmonary fibrosis model. The experimental animals were divided into the treatment group and the prevention group of spearmint, respectively. On the 8th day and the 1st day after modeling, Gavage for 3 weeks and 4 weeks. The body weight and mortality of mice were recorded every 7 days. The lung tissue sections were stained with HE and Masson to observe the degree of airway inflammation and fibrosis. Morphological analysis was performed on the pathological pictures. The levels of hydroxyproline, TNF-α, TGF-β1, MMP-9 and TIMP-1 levels were measured. The expression of α-SMA in lung tissue was measured. Results The 14,42,140 mg · kg-1 Spearmint group could significantly reduce the fibrosis area, some of the alveolar structure was preserved and the alveolar septum collagen deposition was reduced. The Spearmint 14 and 140 mg · kg-1 prophylaxis groups could The levels of hydroxyproline, TGF-β1 and MMP-9 in lung tissue were significantly decreased. Pretreatment with spearmint 14,42,140 mg.kg-1 could significantly decrease the expression of α-SMA in lung. Spearmint oil treatment group except 14 mg.kg-1 group significantly attenuated α-SMA expression of the rest of the indicators had no significant effect. Conclusion Early administration of spearmint oil can reduce bleomycin-induced pulmonary fibrosis in mice by down-regulating the content of MMP-9 and TGF-β1 in the lung tissue, reducing the rupture of basement membrane and decreasing the number of fibroblasts Proliferation and transformation, reduce the myofibroblasts α-SMA expression and extracellular matrix synthesis, play an intervention in the early stage of pulmonary fibrosis.