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目的探讨激光诱导BN大鼠脉络膜新生血管(CNV)形成过程中转化生长因子β1(TGF-β1)及其Ⅰ型受体(TβRⅠ)表达变化趋势及其作用。设计实验性研究。研究对象5组30只雄性BN大鼠。方法BN大鼠单眼视网膜氪激光光凝,诱导CNV形成。分别在光凝后3天,1、2、3、4周摘除眼球,应用免疫组织化学及原位杂交技术检测CNV形成过程中Ⅷ因子相关抗原(FⅧR:Ag)、TGF-β1、TβRⅠ和TGF-β1mRNA的表达及变化。主要指标FⅧR:Ag、TGF-β1、TGF-β1mRNA和TβRⅠ。结果FⅧR:Ag免疫组织化学结果显示,光凝后1周开始形成CNV,3～4周达到高峰。正常BN大鼠TGF-β1、TβRⅠ在视网膜神经节细胞、内核层部分细胞、视网膜色素上皮层表达;TGF-β1mRNA在视网膜神经节细胞、视网膜色素上皮层表达。视网膜光凝后3天～4周,损伤区内FⅧR:Ag阳性染色密度逐渐增加(P<0.05);TGF-β1、TGF-β1mRNA和TβRⅠ阳性染色密度逐渐下降(P<0.05);三者与FⅧR:Ag阳性染色密度负相关(r=-0.87、-0.87、-0.80,P<0.05);TGF-β1和TβRⅠ阳性染色密度正相关(r=0.84,P<0.05)。结论光凝区内TGF-β1合成、分泌不足可能是CNV形成和增殖的主要原因之一;TGF-β1在受体水平表现出调节作用,存在由TβRⅠ介导的生物学效应。TβRⅠ表达低下,信号转导减弱,可能也是CNV形成和增殖的一个重要因素。
Objective To investigate the expression of transforming growth factor β1 (TGF-β1) and its type Ⅰ receptor (TβRⅠ) in choroidal neovascularization (CNV) induced by laser in rat. Design experimental research. Subjects Five groups of 30 male BN rats. Methods Monocular retina krypton laser photocoagulation in BN rats induced CNV formation. The eyeballs were removed 3 days, 1 week, 2 weeks, 3 weeks and 4 weeks after photocoagulation. Immunohistochemistry and in situ hybridization were used to detect the expression of Ⅷ factor related antigen (FⅧR: Ag), TGF-β1, TβRⅠ and TGFβ -β1 mRNA expression and changes. The main indicators of F Ⅷ R: Ag, TGF-β1, TGF-β1 mRNA and Tβ RI. Results The results of FⅧR: Ag immunohistochemistry showed that CNV began to form after 1 week of photocoagulation and peaked at 3 to 4 weeks. TGF-β1 and TβRI in normal BN rats were expressed in retinal ganglion cells, part of the inner nuclear layer and retinal pigment epithelium. TGF-β1 mRNA was expressed in retinal ganglion cells and retinal pigment epithelium. The staining intensity of FⅧR: Ag positive staining increased gradually (P <0.05) in 3 days to 4 weeks after retinal photocoagulation. The positive staining density of TGF-β1, TGF-β1 mRNA and TβRI decreased gradually (P <0.05) FⅧR: Ag positive staining density (r = -0.87, -0.87, -0.80, P <0.05). There was a positive correlation between TGF-β1 and TβRⅠpositive staining density (r = 0.84, P <0.05). Conclusion The synthesis and secretion of TGF-β1 in the photocoagulation zone may be one of the main reasons for the formation and proliferation of CNV. TGF-β1 may play a regulatory role at the receptor level and may have biological effects mediated by TβRI. TβRI expression is low, signal transduction is weakened, may also be an important factor in CNV formation and proliferation.