Suzuki Keiji, Nakazato Kyoumi, Kusakabe Takahiko, Nagamine Takeaki, Sakurai Hiromu, Takatama Masamitu
Geriatrics Research Institute, Faculty of Medicine, Gunma University, Maebashi, Gunma 371-0847, Japan.
Pathol Int. 2007 Mar;57(3):133-9. doi: 10.1111/j.1440-1827.2006.02070.x.
The hypertensive rat brain exhibited softening, severe edema and intracerebral hemorrhage. The NO(2) (-) + NO(3) (-) (NOx) level in the hypertensive rat brain was higher than in the normotensive rat brain. Light microscopy demonstrated severe arterial and arteriolar lesions with fibrinoid deposits and medial lesion. After injecting hypertensive rats with nitroblue tetrazolium (NBT), formazan deposits, which are the reaction product of reduction of NBT by superoxide, were observed in the microvessels and nervous tissue around the microvessels of injured brain. Immunohistochemistry showed that copper zinc superoxide dismutase and manganese superoxide dismutase expression of the endothelial cells of hypertensive rats were also upregulated in comparison with normotensive rat endothelial cells. Inducible nitric oxide synthase and endothelial nitric oxide synthase expression in endothelial cells of normotensive rats were strongly positive, whereas the expression in hypertensive rat endothelial cells was weaker. Nitrotyrosine, a biomarker of peroxynitrite, which is a powerful oxidant formed by the reaction of nitric oxide (NO) with superoxide, was found in the microvessels, injured arteries and arterioles and infarcted brain tissue. Deposition of a major aldehydic product of lipid peroxidation, that is, 4-hydroxy-2-nonenal (4-HNE) was found in microvessels, perivascular tissue, and edematous and infarcted brain. Hypertensive cerebrovascular disease is the result of hypertension-induced oxidative stress.
高血压大鼠的大脑出现软化、严重水肿和脑出血。高血压大鼠大脑中的NO(2) (-) + NO(3) (-)（NOx）水平高于正常血压大鼠大脑。光学显微镜显示严重的动脉和小动脉病变，伴有纤维蛋白样沉积物和中层病变。给高血压大鼠注射硝基蓝四氮唑（NBT）后，在受损大脑微血管周围的微血管和神经组织中观察到甲臜沉积物，这是超氧化物还原NBT的反应产物。免疫组织化学显示，与正常血压大鼠内皮细胞相比，高血压大鼠内皮细胞的铜锌超氧化物歧化酶和锰超氧化物歧化酶表达也上调。正常血压大鼠内皮细胞中的诱导型一氧化氮合酶和内皮型一氧化氮合酶表达呈强阳性，而高血压大鼠内皮细胞中的表达较弱。在微血管、受损动脉和小动脉以及梗死脑组织中发现了硝基酪氨酸，它是过氧亚硝酸盐的生物标志物，过氧亚硝酸盐是一氧化氮（NO）与超氧化物反应形成的一种强氧化剂。在微血管、血管周围组织以及水肿和梗死的大脑中发现了脂质过氧化的主要醛类产物4-羟基-2-壬烯醛（4-HNE）的沉积。高血压性脑血管疾病是高血压诱导的氧化应激的结果。
