尼莫地平和血管内皮生长因子在增生性视网膜病变中作用的实验研究

Experimental study of nimodipine and vascular endothelial growth factor in proliferative retinopathy

目的 研究钙通道拮抗剂尼莫地平在增生性视网膜病变中的治疗作用及其与血管内皮生长因子的相互作用。方法 建立高浓度氧气诱导的SD幼鼠增生性视网膜病变模型 ,球后及腹腔内分别注射不同剂量的尼莫地平。取幼鼠眼球作普通病理切片及免疫组化检测 ,分别检测视网膜新生血管芽内皮细胞数目及VEGF的表达。结果 未用药组视网膜新生血管芽内皮细胞数目及VEGF的表达较正常对照组明显增加 (P <0 0 1) ,球后注药大、中剂量组较未用药组均明显减少 (P <0 0 1) ,小剂量组则无明显变化 (P >0 0 5 )。腹腔内注射各剂量组未用药组均明显减少 (P <0 0 1)。结论 VEGF能够通过激活细胞膜钙通道增加细胞外钙离子内流促进细胞增殖 ,钙通道拮抗剂尼莫地平则通过抑制钙离子内流抑制增殖性病变的发生。尼莫地平在某种程度上能抑制VEGF的表达。

Objective To study the therapeutic effect of the calcium channel antagonist nimodipine on the proliferative retinopathy and it′s interaction with vascular endothelial growth factor (VEGF). Methods A proliferative retinopathy model (OIR) of newborn Sprague-Dawley (SD) rats was induced by hyperoxia. Different dosages of nimodipine were injected to the rats through retrobulbar or intraperitoneal routes. Both eyeballs of newborn rats were enucleated for performing pathological sections and were studied by immunohistochemical method,in order to count the nuclei of proliferative retinal vessels and to investigate the expression of VEGF in the retina. Results The number of nuclei of proliferative retinal vessels and the expression of VEGF in non-treatment group increased significantly as compared with normal control group ( P < 0.01). Both parameters decreased significantly in high dosage and medium dosage of retrobulbar injection group as compared with the non-treatment group ( P <0.01) and there was no significant decrease in low dosage group ( P >0.05). In each dosage group of intraperitoneal injection,there was a significant decrease of the expression of VEGF ( P >0.01). Conclusion VEGF can induce cell proliferation by activating the calcium channel in cell membrane through which the influx of calcium is increased. The calcium channel antagonist nimodipine can inhibit proliferative retinopathy by blocking the influx of calcium. Nimodipine can inhibit the expression of VEGF at certain degrees.