高血脂对血细胞和血管内皮细胞的损伤

The Damages of Blood Cells and Vascuular Endothelial Cell Induced by Blood-lipid Elevation

目的研究血清胆固醇 (cho)升高和氧化低密度脂蛋白 (OX -LDL)在血细胞和血管内皮细胞 (VEC)损伤中的作用。方法采用高胆固醇血症家兔模型研究血清cho对红细胞变形性 ,白细胞自发活化率及粘附分子 (CD11b/CD18)表达的影响。采用人脐静脉内皮细胞 (HUVEC)研究OX -LDL对VEC粘附分子 (ICAM -1、VCAM -1)和MCP-1表达的影响。结果动物模型的结果指出随着血清cho升高 ,红细胞变形性降低 ,白细胞SAR和CD11b/CD18表达增加。由HUVEC获得如下结果 :(1)培养的HUVEC能少量表达ICAM -1和MCP -1及蛋白 ;(2)OX -LDL可显著增强ICAM -1、MCP -1及蛋白表达。对VCAM -1表达无影响 ;(3)OX -LDL有细胞毒性 ,引起VEC形态异常。结论血清cho升高引起红细胞变形性降低 ,白细胞SAR升高 ,活化的白细胞通过释放超氧阴离子自由基 (O·2-)和蛋白酶 ,损伤VEC ,从而破坏内皮的完整性。因此 ,血清cho升高是AS和心、脑血管病的重要危险因素之一。

Objective To study the role of elevated serum cholesterol (cho) and oxidized low desity lipoprotein(OX_LDL) in the damaged blood cells and vascular endothelial cell(VEC).Methods The effects of serum cho on erythrocyte deformability, spontaneous activating rate(SAR) of leukocyte and expression of adhesion molecule (CD11b/CD18)were examined by hypercholesterolemic rabbits, The effects of OX_LDL on expression of VEC adhesion molecules (ICAM-1.VCAM-1) and MCP-1 were examined by human umbilical vein endothelial cell(HUVEC).Results The results from hypercholesterolemic rabbits indicated that erythrocyte deformability was markedly decreased, leukocyte SAR and expression of CD11b/CDl8 were markedly increasied accompanied by serum cho elevation. The results were obtained by HUVEC as follows: 1. Cultured HUVEC only expressed ICAM-1 and MCP-1 protein in small numbers; 2. OX_LDL (200μg/ml) induced further strong expression of ICAM-1 and MCP-1 protein; 3. OX_LDL possess cytotoxic effects. The abnormal changes of cell morphology were induced by OX_LDL. Conclusions EIevated serum cho causes erythrocyte deformability decrease and leukocyte SAR elevation, activated leukocytes adhere to and damage adjacent endothelial cells and releasing harmful substances, such as proteases and free radicals, subsequently disrupting endothelium integrety. Therefore elevated serum cho is an important risk factor for atherosclerosis, cardio and cerebrovascular diseases.