活性维生素D3对大鼠肺纤维化中蛋白激酶D1介导的抗氧化通路的影响

Impact of active vitamin D3 on antioxidant pathways mediated by protein kinase Dl in rats with pulmonary fibrosis

目的：探讨肺纤维化发生发展中蛋白激酶D1（PKD1）介导的线粒体抗氧化通路的作用以及活性维生素D3在纤维化过程中对该通路的影响。方法：雄性SD大鼠随机分成对照组、模型组和治疗组。应用实时荧光定量PCR和免疫组织化学分别从mRNA和蛋白质水平检测大鼠肺组织中PKD1、核转录因子（NF-κB）和锰超氧化物歧化酶（MnSOD）的表达。结果：在第14天，治疗组和模型组中PKD1、NF-κB和MnSOD的表达量都显著低于对照组，而治疗组中3种因子的表达量又明显高于模型组；在第21天，3种因子在模型组和治疗组中的表达量明显高于对照组。在第28天，3种因子在模型组和治疗组中的表达量与对照组相比两两之间均没有差异。结论：PKD1-MnSOD线粒体抗氧化通路在博莱霉素引起的大鼠肺纤维化早期发挥重要作用，活性维生素D3能够上调这一抗氧化通路，具有一定的抗氧化作用，对大鼠肺纤维化的发生发展具有一定的抑制作用。

Objective： To explore the effects of mitochondrial antioxidant pathway mediated by protein kinase D1 （PKD1） on genesis and development of pulmonary fibrosis, and the effect of active vitamin D3 on this pathway during the pathogenesis of fibrosis. Methods： Male SD rats were randomly divided into control group, model group, treatment group. The mRNA and protein expression of PKD1, nuclear transcription factor κB （NF-κB） and manganese superoxide dismutase （MnSOD） were detected by real time PCR and immunohistochemical technology respectively. Results： On the 14th day, mRNA and protein expression of PKD1, NF-κB and MnSOD in control group were significantly higher than that in model group and treatment group, and the expression of the three genes in treatment group was significantly higher than model group. On the 21st day, expression levels of the three genes in the model group and treatment group were all higher than that in control group. On the 28th day, although the expression of three kinds of genes in the treatment group and model group seemed higher than that in control group, but no significant difference was found. Conclusion： Mitochondrial antioxidant pathway mediated by PKD1 plays an important role at early stage of pulmonary fibrosis induced by bleomycin. The active vitamin D3, may promote the PND1-MnSOD antioxidant pathways during genesis and development of pulmonary fibrosis, suggesting that it plays a certain role during antioxidant process and inhibition of pulmonary fibrosis in rats.