摘要
目的:研究间歇缺氧(IH)对血管性痴呆(VD)大鼠认知能力的影响及其可能机制。方法:48只Wistar大鼠分为假手术组(对照组)、IH组、VD组和VD+IH组。双侧颈总动脉结扎法制备VD模型,4周后,IH组、VD+IH组给予IH处理4周;通过生物化学法检测海马超氧化物歧化酶(SOD)活性和丙二醛(MDA)的含量,TUNEL法检测海马神经元凋亡,RT-PCR检测bcl-2和baxmRNA,Y形迷宫测试大鼠学习、记忆能力。结果:与对照组相比,IH组海马MDA含量增多而SOD活性降低;VD组bcl-2和baxmRNA表达增加;IH组和VD组均出现明显的CA1区神经元凋亡和迷宫测试中大鼠电击次数的增加(P<0.05)。VD+IH组与其它3组相比,海马MDA增多及SOD减少更为明显,bcl-2/baxmRNA比值显著降低,海马CA1区神经元的凋亡比例(32.83%±6.13%)高于IH组(9.91%±3.17%)、VD组(15.28%±3.71%)和对照组(2.03%±1.42%),迷宫测试中大鼠电击次数增加(P<0.05)。结论:IH通过加重大鼠海马氧化应激损伤,促进VD大鼠海马凋亡相关基因的表达,加重了海马神经元的迟发性死亡和VD大鼠的认知损害。这可能是慢性脑缺血病人伴随睡眠呼吸暂停低通气综合征后,认知损害加剧的重要机制之一。
AIM ： To study the influence of intermittent hypoxia on vascular dementia （VD） and its mechanism. METHODS ： A chronic ischemia model was made by permanent bilateral carotid arteries occlusion. Four weeks later, intermittent hypoxia was given to mimic sleep apnea syndrome in the following 4 weeks. For all the experiments, 8 h/d IH profiles consisted of alternating room air （21% oxygen） and 7% oxygen every 30 s. Then, the hippocampuses were prepared for measuring superoxide dismutase （ SOD ） and malondialdehyde （ MDA ） （ biochemical methods ）, apoptosis （TUNEL）, bcl -2 and bax mRNA （reverse -transcriptase PCR） and cognitive function （Y -type maze）. RESULTS： In hippocampus, four - week intermittent hypoxia led to the increase in MDA [ （ 1.64±0. 12） mmol/g vs （ 1.32 ±0. 09） mmol/g in sham], decrease in SOD [ （67.83 ± 7. 13 ） × 10^3 U/g vs （ 121.00 ± 21.37 ） × 10^3 U/g in sham ], increase in neuronal apeptosis （9.91% ±3. 17% vs 2.03% ± 1.42% in sham） and learning/memory damage. The chronic hypoperfusion induced the increase in bcl -2 and bax mRNA, neuronal apoptosis （15.28% ± 3. 71% ）, and learuing/memory damage either. Intermittent hypoxia enhanced the damage of chronic ischemia, with increased MDA [ （2. 41 ± 0. 22） mmol/ g], decreased SOD [ （43.00 ± 16. 94） × 10^3U/g], down -regulated bc1-2/bax mRNA ratio and enhanced neuronal apoptosis （32. 83% ± 6. 13% ）, finally aggravated the cognitive impairment of rats suffering VD. CONCLUSION： Intermittent hypoxia increases the damage of VD rats through aggravating the oxidative stress and enhancing regulation of apoptosis related gene, which can partly explain the mechanism of the enhanced cognitive impairment in chronic ischemic patients accompanied with obstructive sleep apnea hyponea syndrome.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2009年第10期1922-1925,共4页
Chinese Journal of Pathophysiology
基金
湖北省科技攻关计划资助项目(No.2006AA301B51-2)
