高同型半胱氨酸血症对大鼠缺血性病变的影响

Effect of hyperhomocysteinemia on ischemic disease in rats

目的探讨高同型半胱氨酸血症(HHcy)对大鼠缺血性病变的影响。方法32只SD大鼠随机分为对照组(n=16,每日给予正常饮水)和高同型半胱氨酸组(HH组,n=16,每日给予含1 g/kg蛋氨酸的饮用水)。饮水14 d后,手术切除左侧股动、静脉造成单侧下肢缺血模型,继续按各组的饮水方法15 d后观察相关血清生化指标;测定缺血肌肉组织中一氧化氮(NOx)和环磷酸鸟苷(cGMP)的含量;免疫组化法测定双下肢肌肉毛细血管密度;血管造影法观察缺血下肢血管新生的情况。结果术后第15天,HH组血清高密度脂蛋白-胆固醇(HDL-C)、尿素氮、尿酸及尿素氮/血肌酐明显高于正常组;而叶酸、维生素B12、HDL-C和内生肌酐清除率显著低于对照组(P<0.05或P<0.01);HDL-C与同型半胱氨酸呈显著负相关(P<0.05);毛细血管密度和血管造影毛细血管评分记数均显著低于对照组(P<0.01,P<0.05);组织中的NOx和cGMP含量均显著低于对照组(P<0.05,P<0.01)。结论HHcy不仅可抑制大鼠缺血组织的自我修复,还能降低高密度脂蛋白的浓度,并且导致大鼠不同程度的肾功能损害,多方面加重疾病的进程。

Objective To evaluate the effect of hyperhomocysteinemia on ischemic diease in rats. Methods Thirty-two SD rats were randomized into two groups, control group （n = 16, administered with tap water） and hyperhomocysteinemia group（HH group, n = 16, administered with water containing L-methionine at 1 g/kg/d）. At the 14^thday of dietary modification, the left femoral artery and vein were excised, and the interventions continued for another 14 days. At the 15th day after operation, serum biochemical parameters as well as NOx and cGMP in ischemic tissues were tested, capillary vessel density of both hindlimbs were measured by histological analysis, and angiogenesis of ischemic hindlimb was observed by angiography. Results At the 15th day after operation, the level of high-density lipoprotein-cholesterol（HDL-C） , blood urea nitrogen, uric acid and ratio of blood urea nitrogen to serum creatinine were significantly higher in HH group than those in control group, while the level of serum folic acid, VitB12, HDL-C and endogenous creatinine clearance rate were significantly lower in HH group than those in control group （P 〈 0.05 or P 〈 0.01 ）. HDL-C had a negative correlation with Hcy-C （P 〈0.05 ）. Capillary vessel density and angiographic score in the ischemic limbs were significantly lower in HH group than those in control group （ P 〈 0.01, P 〈 0.05）. And the contents of NOx and cGMP in ischemic tissue were significantly lower in HH group than those in control group （ P 〈 0.05, P 〈 0.01 ）. Conclusion Hyperhomocysteinemia can inhibit the recovery of ischemic tissue in rats, decrease the level of serum high-density lipoprotein and induce the injury of renal function to some extent, which contribute to the development of disease.