高血压大鼠视网膜和肾脏微血管损害的实验研究

PATHOLOGIC CHANGES OF RETINAL CAPILLARIES AND GLOMERULAR CAPILLARIES IN EXPERIMENTAL HYPERTENSION

目的探讨高血压大鼠视网膜和肾脏微血管损害及两者的关系。方法手术切除大鼠一侧肾脏 ,部分结扎另一侧肾动脉 ,建立高血压动物模型 ,对照组模拟手术。活体检查大鼠眼底 ,检测肾功能 ,采用常规光镜组织化学染色、免疫组织化学染色、电镜和组织化学电镜等技术 ,观察大鼠术后 2周、1个月、2个月、4个月 4个不同时间点视网膜和肾脏微血管的改变。结果①高血压大鼠眼底和肾功能从术后 2个月起即有明显损害 ;②高血压大鼠视网膜毛细血管基底膜 (retinalcapillarybasementmembrane ,RBM)和肾小球毛细血管基底膜 (glomerularcapillarybasementmembrane ,GBM )从术后 2个月起即普遍增厚 ;③高血压大鼠RBM和GBM的增厚伴有其构成成分Ⅳ型胶原和层粘连蛋白的增多 ,并伴有RBM和GBM上负电荷位点数目的减少 ;④高血压大鼠视网膜毛细血管和肾小球毛细血管分别在术后 2周和 1个月时出现内皮细胞下水肿 ,与基底膜脱离的现象 ;⑤高血压大鼠病程 4个月时视网膜毛细血管周细胞水肿变性 ,肾小球毛细血管上皮细胞病变较轻。结论高血压大鼠视网膜和肾脏损害有共同的病理学基础 :毛细血管内皮细胞下水肿 ,与基底膜脱离 ;基底膜增厚 ,伴有其上负电荷位点数目的减少。

ObjectiveTo investigate the pathological spectrum of retinal and glomerular capillaries in experimental hypertension, and their relationship. MethodsSystemic hypertension was produced experimentally in SD rats by partially constricting the right renal artery and removing the left kidney. The eyes and the tissues of the residual kidney obtained from hypertensive animals at 2 weeks, 1, 2, 4 months were examined by means of light microscopy, immunohistochemical staining, electron microscopy and histochemical electron microscopy and compared with the control group.Results① Hypertensive retinopathy and damages of renal functions were emerged from 2 months after surgery. ② From 2 months after surgery, thickening of retinal capillary basement membrane (RBM) and glomerular capillary basement membrane (GBM) became apparent. ③ From then on, RBM and GBM showed increased staining reaction for type Ⅳ collagen and laminin, while staining reaction of RBM and GBM for fibronectin in hypertensive rats was negative at any stages. The number of anionic sites within the RBM and GBM were gradually reduced following the development of hypertension and they were definitely decreased at 4 months. ④ A few deteriorated endothelial cells were lifted focally from the RBM and GBM with subendothelial swelling in retinal vessels and glomerular capillaries at 2 weeks and 1 month. ⑤ The pericytes exhibited edema and deterioration in retinal vessels at 4 months, epithelial changes of glomerular capillary were relatively slight. ConclusionHypertensive retinopathy and renal injury are partly based on the same pathologic process: detachment of the endothelial cells from the RBM and GBM, thickening of the RBM and GBM companied with the reduction of anionic sites ;pathologic changes of retinal and glomerular capillaries have also their distinctness:pericytic swelling and degeneration are seen seriously, epithelial changes of glomerular capillary are relatively slight.