血红素加氧酶-1在大鼠矽肺纤维化中的作用

The role of HO-1 in silicosis fibrosis in rats

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（ HO-1） in silicosis fibrosis in rats. Methods Sixty Wistar rats were randomly divided into the control group（ group A）,silicon dioxide group（ group B）,silicon dioxide ＋ HO-1inhibitor（ zinc protoporphyrin） group（ group C） and silicon dioxide ＋ HO-1 inducer（ cobalt protoporphyrin） group（ group D）. Silica suspension was instilled by tracheal exposure to duplicate the rat models with silicosis in group B,C and D. The rats in group C and group D were intraperitoneally injected with 12. 5mg /kg zinc protoporphyrin and cobalt protoporphyrin respectively,qod for 28 days. Then,lungs were collected and the pathological structures of lung tissues were observed by the HE staining. The HO-1 protein content in lung tissues was measured by Western blot analysis and HO-1mRNA expression was detected by fluorescent quantitative PCR. Results Compared with the control group,the lung tissues in group B displayed typical pathological changes of silicosis fibrosis. The changes in group C were aggravated and those in group D were alleviated. The expression of HO-1 in the control group was significantly lower than those of other groups（ P〈0. 05）. The expression of HO-1 in group C was significantly lower than that of group B,while the expression in group D was significantly higher than that of group B（ P〈0. 05）.RT-PCR detection showed that the relative expression levels of HO-1 mRNA in group A,B,C and D were 1,2. 25 ± 0. 38,1.81 ± 0. 74 and 7. 75 ± 0. 56 respectively,indicating significantly lower HO-1mRNA expression in group C than in group B,and higher expression in group D than in group B（ P〈0. 05）. Conclusions HO-1 participates in the formation of silicosis fibrosis in rats,and the extent of silicosis fibrosis in rats can be changed by the intervention of HO-1. It can provide a new approach for the diagnosis and treatment of silicosis fibrosis.