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目的观察血红素加氧酶-1在大鼠矽肺纤维化中的作用。方法 Wistar大鼠60只,随机分为4组,分别为对照组(A组)和染尘模型组(B组)、B组+HO-1抑制剂(锌原卟啉)组(C组)、B组+HO-1诱导剂(钴原卟啉)组(D组)。采用气管暴露法滴注二氧化硅悬液制造大鼠矽肺模型。C、D组分别腹腔注射锌原卟啉12.5 mg/kg、钴原卟啉5 mg/kg,隔日一次,连续4周后,取肺,HE染色观察各组肺组织病理结构,Western blot检测各组肺组织HO-1蛋白含量,荧光定量PCR检测各组肺组织HO-1mRNA的表达。结果与对照组比较,B组出现典型的矽肺纤维化的病理改变,C组较B组加重,D组较B组改善;对照组中HO-1蛋白表达明显低于其他各组(P<0.05),抑制剂C组较B组HO-1蛋白表达明显降低,而诱导剂D组较B组HO-1蛋白表达量明显升高(P<0.05)。RT-PCR检测A、B、C、D组HO-1 mRNA相对表达量分别为1、2.25±0.38、1.81±0.74、7.75±0.56,抑制剂C组较B组表达明显降低,而诱导剂D组较B组表达显著升高(P<0.05)。结论 HO-1参与了大鼠矽肺纤维化的形成过程,通过对其干预可以改变大鼠矽肺纤维化的程度,可为矽肺纤维化的诊断与治疗提供新途径。
Objective To observe the role of heme oxygenase-1 in silicotic fibrosis in rats. Methods Sixty Wistar rats were randomly divided into four groups: control group (group A) and model group (group B), group B + HO-1 inhibitor (zinc protoporphyrin) group (group C) , B group + HO-1 inducer (cobalt protoporphyrin) group (D group). Rat model of silicosis was made by instillation of silica suspension by tracheal exposure. Groups C and D were intraperitoneally injected with zinc protoporphyrin 12.5 mg / kg and cobalt protoporphyrin 5 mg / kg once every other day for 4 weeks. Lung and HE staining were performed to observe the histopathology of the lungs. Group HO-1 protein content in lung tissue, fluorescence quantitative PCR detection of HO-1mRNA expression in the lung tissue of each group. Results Compared with the control group, the pathological changes of the typical silicosis of fibrosis were observed in group B, which were more severe in group C than in group B, and were improved in group D compared with group B. The expression of HO-1 protein in control group was significantly lower than that in other groups (P <0.05 ). The HO-1 protein expression in group C was significantly lower than that in group B, while the HO-1 protein expression in group B was significantly higher than that in group B (P <0.05). The relative expression levels of HO-1 mRNA in group A, B, C and D by RT-PCR were 1, 25.25 ± 0.38, 1.81 ± 0.74 and 7.75 ± 0.56, respectively. The expression of HO-1 mRNA in group C was significantly lower than that in group B Compared with B group, the expression was significantly increased (P <0.05). Conclusion HO-1 is involved in the formation of silicotic fibrosis in rats. Intervention with HO-1 can change the degree of silicosis in rats, which may provide a new way for the diagnosis and treatment of silicosis.