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[目的]探讨矽肺发病过程中肺内淋巴管增生与纤维化进程的关系。[方法]56只Wistar大鼠随机分为矽肺模型组和对照组,模型组又按动物处死时间分为1、7、14、28、42和56 d 6个亚组,每组8只大鼠。采用墨汁-硝酸银染色观察淋巴管增生情况,实时荧光定量PCR方法检测VEGFR-3 m RNA转录水平,免疫组化法、比色法检测肺组织中I型胶原表达及羟脯氨酸含量。[结果]与对照组相比,矽肺大鼠肺组织中I型胶原从染尘后1 d、羟脯氨酸含量从染尘后7 d即开始升高(P<0.05或P<0.01);从染尘7 d开始发现增生的淋巴管,且随着染尘时间的延长,淋巴管增生呈现先增多后减少的趋势;VEGFR-3 m RNA表达在染尘后7 d开始增加(P<0.01)。Pearson相关性分析显示在染尘早期,即28 d以前,I型胶原含量、羟脯氨酸含量与VEGFR-3水平呈正相关(r=0.974 4,P=0.025 6;r=0.998 5,P=0.001 5),染尘28 d后I型胶原含量、羟脯氨酸含量与VEGFR-3水平呈负相关(r=-0.975 1,P=0.024 9;r=-0.974 4,P=0.025 7)。[结论]矽肺大鼠发病过程中出现肺组织淋巴管增生,其增生程度与矽肺纤维化具有相关性。
[Objective] To investigate the relationship between lymphangiogenesis and fibrosis in the pathogenesis of silicosis. [Methods] Fifty-six Wistar rats were randomly divided into silicosis model group and control group, and the model group was divided into 6 sub-groups of 1, 7, 14, 28, 42 and 56 d according to the time of sacrificial animals, 8 rats in each group . The proliferation of lymphatic vessels was observed by ink-silver nitrate staining. The transcription level of VEGFR-3 mRNA was detected by real-time fluorescence quantitative PCR. The expression of type I collagen and the content of hydroxyproline in lung tissue were detected by immunohistochemistry. [Result] Compared with the control group, the content of hydroxyproline of type I collagen in lung tissue of silicosis rats increased from the first day after being dyed for 7 days (P <0.05 or P <0.01). Proliferation of lymphatic vessels began to be detected on the 7th day, and the lymphatic vessel proliferation increased firstly and then decreased with the prolongation of the dying time. The expression of VEGFR-3 mRNA began to increase at 7th day (P <0.01) ). Pearson correlation analysis showed that type I collagen and hydroxyproline contents were positively correlated with VEGFR-3 levels at the early stage of dying, ie 28 d (r = 0.974 4, P = 0.025 6; r = 0.998 5, P = 0.001 5). The content of collagen I and the content of hydroxyproline were negatively correlated with the level of VEGFR-3 after 28 days of dying (r = -0.975 1, P = 0.024 9; r = -0.974 4, P = 0.025 7) . [Conclusion] Lymphangiogenesis of lung tissue occurs in the pathogenesis of silicosis rats, and the degree of hyperplasia is correlated with silicosis fibrosis.