氧化低密度脂蛋白在尿酸致早期慢性肾脏疾病血管内皮损伤中的作用

The Effect of ox-LDL on Endothelial Dysfunction in Early Chronic Kidney Diseases with Hyperuricemia

目的:探讨氧化低密度脂蛋白(ox-LDL)在尿酸所致早期慢性肾脏疾病(CKD)血管内皮损伤中的作用。方法:30只雄性SD大鼠随机分为3组:A组(假手术组,n=10),B组(右肾切除组,n=10)和C组(右侧肾切除+氧嗪酸钾灌胃组,n=10)。检测血清尿酸(UA)、肌酐(Scr)、一氧化氮(NO)、内皮素-1(ET-1)、ox-LDL等指标。光镜观察血管壁病理损害。分析ox-LDL水平与UA、NO、ET-1、NO/ET-1比值的相关性。结果:(1)3组大鼠肾病理均未见明显病变,且血肌酐无明显差异,但C组血尿酸水平明显升高(P<0.01);(2)A组血管壁未见明显病变;C组可见内皮细胞脱落,内皮间隙增宽,细胞水肿,管壁炎症细胞聚集,血管中层平滑肌细胞增生明显,结构紊乱;B组病变与C组相似,但程度较轻。C组NO明显低下(P<0.01),ET-1明显增高(P<0.05),NO/ET-1比值明显降低(P<0.01);(3)单因素相关分析显示:尿酸与ET-1呈显著正相关(r=0.9374,P<0.01),与NO(r=-0.9462,P<0.01)、NO/ET-1比值(r=-0.9230,P<0.01)呈显著负相关;⑷C组ox-LDL水平显著升高(P<0.05),ox-LDL与尿酸(r=0.8479,P<0.01)、ET-1(r=0.7900,P<0.01)呈显著正相关,与NO(r=-0.7459,P<0.05)、NO/ET-1比值(r=-0.7949,P<0.01)呈显著负相关。结论:尿酸可致早期CKD血管内皮细胞损伤和功能紊乱,ox-LDL在其发生发展中可能起重要作用。

Objective：To evaluate the effect of oxidized low density lipoprotein （ox-LDL） on endothelial dysfunction in early chromic kidney diseases （CKD） with hyperuricemia. Methods：Thirty SD rats were divided into Group A（shame-operative,n=10） and Group B（right-side nephrectomy,n=10） and Group C（right-side nephrectomy and fed with potassium oxonate,n=10）.We measured the indices including serum creatinine （Scr）,serum uric acid （UA）,serum nitric oxide（NO）,serum endothelin-1（ET-1）,serum oxidative modified low density lipoprotein （ox-LDL）,the pathology of kidney and artery in the experimental group,and then compared these indices with those in the other two groups. Results：（1）There was no obvious pathological change in the kidney of the three groups. Compared with Group A and Group B,Group C had significant higher level of UA,but there was no obvious difference in the level of Scr among the three groups.（2）There was no obvious pathological change in the artery of Group A. However,in Group C,the endothelial cells partly dropped from the artery,and the gap between them broadened. The smooth muscle cells proliferated in Group C significantly. The pathological change in the artery of Group B was similar to that of Group C,but was more minor. Group C had significant lower level of serum NO （P0.01） ,lower level of NO/ET-1 ratio（P0.01）,higher level of serum ET-1（P0.05）. （3） Linear regression analysis showed that the level of UA had significant positive correlation with serum ET-1（r=0.9374,P0.01）,but negative correlations with serum NO （r=-0.946 2,P0.01）and NO/ET-1 ratio（r=-0.9230,P0.01）. ⑷ Group C had significant higher level of serum ox-LDL（P0.05）.The level of ox-LDL had significant positive correlations with UA（r=0.8479,P0.01） and ET-1（r=0.7900,P0.01）,but negative correlations with NO（r=-0.7459,P0.05） and NO/ET-1 ratio（r=-0.7949,P0.01）. Conclusions：Hyperuricemia can lead to the damage and dysfunction of endothelial cells even in early CKD,and ox-LDL may play an important role in its development.