血管内皮功能障碍与阿尔茨海默病的关系

Endothelial dysfunction with Alzheimer's disease

目的探讨血管内皮功能与早期阿尔茨海默病(Alzheimer disease,AD)的关系。方法收集45例轻中度 AD 患者和48名健康对照,应用高效液相色谱技术和试剂盒检测血浆生化指标。结果与健康对照组相比,AD 组患者血浆不对称性二甲基精氨酸(ADMA)水平明显升高[(0.95±0.09)μmol/L,P=0.00],血浆一氧化氮合酶(NOS)活性[(13.9±3.9)U/L]、诱导型 NOS(iNOS)活性[(5.1±1.8)U/L]及 NO 的含量[(41.7±5.0)μmol/L]显著降低(P=0.00);Logistic 回归分析发现 AD 组患者血浆 NO 水平与临床痴呆评定量表评分呈正相关(y=36.64+0.398x;r=0.398,P=0.007);血浆 ADMA 水平与 iNOS 的活性呈负相关(y=1.041-0.354x;r=-0.354,P=0.017)。结论 AD 患者在早期即出现了血管内皮功能障碍的生化改变,ADMA 抑制 iNOS 活性而干扰 NO 的合成是 AD 患者内皮功能障碍的机制之一。

Objective To explore the relation between endothelial function and Alzheimer＇ s disease （AD）. Methods The concentration of asymmetric dimethylarginine （ADMA） and L-arginine were measured by high-performance liquid chromatography （HPLC）, the concentration of nitric oxide （NO） detected by the method of nitrate reductase, and the activity of nitric oxide synthase （NOS） examined using NOS assay kits, in the plasma of 45 mild/moderate AD patients and 48 controls. Results Compared with controls, the concentration of ADMA（0. 95 ± 0. 09 μmol/L, P = 0. 00） was significantly increased, however the activity of NOS （（13.9±3.9）U/L, P=0.00）, inducible NOS （iNOS） （（5.1 ±1.8 ）U/L, P= 0. 00） and concentration of NO （（41.7 ＋ 5. 0） μmol/L, P = 0. 00） were significantly decreased. In addition, Logistic regression analysis found significant positive correlations between the plasma concentration of NO and the score of the CDR（y = 36. 64 ±0. 398x; r = 0. 398, P 〈 0. 01 ）, and a highly significant negative correlation seen between the plasma concentration of ADMA and the activity of iNOS （y = 1. 041 - 0. 354x; r = - 0. 354, P 〈 0. 01 ） in AD patients. Conclusions Increased concentrations of circulating ADMA, decreased concentrations of NO and decreased activity of NOS and iNOS were found in the plasma of early stage in AD patients. ADMA mainly inhibited the activity of iNOS to decrease the circulating concentration of NO, which indicated that endothelial dysfunction involved in the pathogenesis of AD.