摘要
高同型半胱氨酸血症是引起动脉粥样硬化的一种独立危险因素。过量服用蛋氨酸会导致血清中同型半胱氨酸浓度增高、内皮功能受损、血管舒缩功能减弱。本研究使用过量服用蛋氨酸导致高同型半胱氨酸血症大鼠 ,与对照组比较 ,观察缺血下肢血管新生的情况 ,判断高同型半胱氨酸血症对缺血性血管新生的影响。将 36只雄性Sprague Dawley大鼠分为两组 :对照组和高同型半胱氨酸血症组。对照组始终给予自来水 ;高同型半胱氨酸血症组则给予含有 0 .5 %蛋氨酸的饮水。两组动物分别按上述方法给予不同饮水 2周后 ,手术切除左侧股动、静脉 ,观察缺血 2 8d内缺血区域血管新生和侧枝血管形成的情况。过量服用蛋氨酸导致的高同型半胱氨酸血症减弱了大鼠下肢慢性缺血性血管新生和侧枝血管的建立 ,这可能与高同型半胱氨酸血症减弱内皮源性一氧化氮生物活性有关。
Aim Elevated plasma homocysteine impairs vasomotor regulation. Hyperhomocysteinemia (HH) is an independent risk factor for atherosclerosis, which causes peripheral arterial occlusive disease. Thus, we examined whether HH induced by oral methionine load modulated in vivo angiogenesis in a rat model of hindlimb ischemia. Methods Male Sprague-Dawley rats were divided into 2 groups: the control group was given tap water, and the other group was made HH by daily intake of L-methionine (1 g/kg body weight) in drinking water. At the 14th day of the dietary modification, the left femoral artery and vein were excised, and the extents of angiogenesis and collateral vessel formation in the ischemic hindlimb were examined for subsequent 4 weeks. Results Plasma homocysteine levels significantly increased, and plasma levels of nitric oxide and tissue contents of nitric oxide and cyclic guanosine 3, 5-monophosphate significantly decreased in the HH group. Serial laser Doppler blood perfusion analysis revealed significant decrease in the ratio of ischemic/normal hindlimb blood perfusion at postoperative days 7,14,21 and 28. Postmortem angiography of the ischemic limb revealed a significant decrease in the angiographic score at postoperative day 14 in the HH group. Finally, immunohistochemical examination of the ischemic tissue sections showed a significant decrease in capillary density in the HH group. Conclusions In summary, oral methionine-induced HH impairs ischemia-induced angiogenesis and collateral vessel formation in a rat model of chronic hindlimb ischemia. The mechanism appears to be mediated at least in part by decreased bioavailability of endothelium-derived nitric oxide (EDNO) in the HH state.
出处
《中国动脉硬化杂志》
CAS
CSCD
2003年第6期493-497,共5页
Chinese Journal of Arteriosclerosis
基金
TheministryofEducation
Science
SportsandCultureofJapan( 10 770 3 3 6)
中国留学回国人员科研启动基金 ( 2 0 0 2 2 74 0 2 )资助
