【摘要】 目的观察高同型半胱氨酸(HHcy)模型兔软脑膜微血管口径、白色微小血栓(白微栓)数量和血管内皮功能变化及其相关分析。方法采用L-蛋氨酸皮下注射法建立HHcy家兔模型,应用"颅骨窗口法"和微循环闭路检测系统观察其软脑膜微血管中白微栓数量及微血管口径变化;采用柱前衍生反相高效液相色谱-荧光法检测同型半胱氨酸(Hcy)浓度;平行观测血管内皮功能指标血管性血友病因子抗原(vWF,用酶联免疫吸附法)、血浆内皮素-1(ET-1,用ELISA)、血清一氧化氮(NO,用化学比色法)水平;并对HHcy所致ET-1、NO血液浓度变化和微血管口径变化进行相关分析。结果与正常对照组比较,HHcy模型兔软脑膜微血管中白微栓数量增加(23.00±6.00个/minvs4.00±1.00个/min,P<0.01),伴微血管口径缩小(80.80±6.30μmvs110.20±7.20μm,P<0.01),ET-1明显增加(168.40±13.20ng/Lvs93.25±13.20ng/L,P<0.01),NO明显降低(22.83±3.53μmol/Lvs38.31±3.20μmol/L,P<0.01);vWF有所增加,但无显著性差异(127.10±32.33%vs119.55±43.56%,P>0.05)。相关分析显示,模型兔Hcy水平升高与ET-1血浆浓度成正相关(r=0.727,P<0.01);与NO血清浓度成负相关(r=-0.48,P<0.05)。模型组ET-1含量升高时,微血管收缩明显,两者呈明显负相关(r=-0.56,P<0.05);而NO与ET-1的变化相反,微血管收缩时,NO含量降低,微血管扩张时,NO含量升高,两者呈良好正相关关系(r=0.613,P<0.05)。结论HHcy兔软脑膜微血管口径变化及白微栓增多与HHcy引起的微血管内皮功能紊乱、ET-1/NO等活性物质的合成与分泌失调有关。更多还原

【Abstract】 Objective To investigate the change of white microthrombus and vascular endothelium function in pia mater microvessel of rabbit model with hyperhomocysteinemia(HHcy). Methods The rabbit model with hyperhomocysteinemia was established by L-methionine subcutaneouse injection. The changes of white microthrombus and microvascular diameter in pia mater microvessel were observed by using cranial window(CW) method and closed microcirculation detection system,The concentration of Hcy was detected by high performance liquid,The level of von Willebrand factor(VWF),endothelin-1(ET-1) were assayed by ELISA. The content of NO was measured by nitrate reduction method. Meanwhile,the relationship between the changes of microvascular diameter and blood concentration ET-1,NO was analyzed. Results Compared with control group,the amount of white microthrombus was increased(23.00±6.00/min vs 4.00±1.00/min,P<0.01) and microvascular diameter was contracted(80.80±6.30 μm vs 110.20±7.20 μm,P<0.01),the level of ET-1 was higher in HHcy group than control group(127.10±32.33% vs 93.25±13.20%,P<0.01) and NO level was decreased(22.83±3.53 μmol/L38.31±3.20 μmol/L,P<0.01); while the level of vWF was 127.10±32.33% vs 119.55±43.56,P>0.05. Correlation show when the level of ET-1 was high in HHcy group,microvessel markedly contracted. The level of ET-1 was negatively correlated with microvascular diameter(r=-0.56,P<0.05). However,the content of NO was contrary to the change of ET-1 level,microvascular contraction was associated with the decline of NO,while microvessel was expanded,the content of NO was increased. Microvascular diameter was positively correlated with the content of NO(r=0.613,P<0.05). Conclusion The changes of white microthrombus and microvascular diameter in rabbit model with hyperhomocysteinemia might be related to the microvessel endothelium dysfunction and the malajustment of the synthesis and secretion of ET-1 and NO.更多还原