Increased HO-1 expression and decreased NOS expression in the hippocampus from adult spontaneously hypertensive rats

Increased HO-1 expression and decreased NOS expression in the hippocampus from adult spontaneously hypertensive rats
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DOI:
10.1385/cbb:46:1:35
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发表时间:
2006-01-01
影响因子:
2.6
通讯作者:
Wang, R.
Wang, R.
中科院分区:
生物学4区
文献类型:
--
作者:
Huang, Y.;Wu, L.;Wang, R.

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高血压时血红素氧合酶(HO)和一氧化氮合酶(NOS)的表达可能参与了血管性痴呆等高血压相关神经元疾病的发病机制。本研究采用免疫印迹法检测了自发性高血压大鼠(SHR)海马HO和NOS的表达水平。高血压前期4周SHR海马内诱导型HO-1的表达水平约为同龄SD大鼠的2倍(p < 0.01)。23周龄高血压大鼠海马HO-1水平显著高于同龄SD大鼠(p < 0.05),但与4周龄SHR无显著差异。不同年龄SHR和SD大鼠海马HO-2表达水平无差异。23周龄SHR海马HO总酶活性显著高于同龄SD大鼠和4周龄SD/SHR(p < 0.01)。23周龄SHR海马nNOS蛋白表达无明显变化,但iNOS表达较同龄SD大鼠和4周龄SD/SHR低约4倍(p < 0.01)。23周龄SHR海马NOS总酶活性显著低于同龄SD大鼠和4周龄SD/SHR(p < 0.01)。与年龄匹配的SD大鼠相比,23周龄SHR的Morris水迷宫表现明显受到抑制。由于SHR已被用作血管性痴呆的模型和海马是必不可少的空间学习和记忆,在成年SHR的海马改变HO/CO和NOS/NO系统的理解可能会揭示与血管性痴呆相关的记忆缺陷的发病发展。
Brain expression of heme oxygenase (HO) and nitric oxide synthase (NOS) in hypertension may participate in the pathogenesis of hypertension-related neuronal disorders, such as vascular dementia. In the present study, expression levels of HO and NOS in spontaneously hypertensive rats (SHR) were investigated using Western immunoblotting assay. Expression level of inducible HO-1 in hippocampus of 4-wk prehypertensive SHR was about twofold of that in age-matched Sprague-Dawley (SD) rats (p < 0.01). In 23-wk SHR with fully developed hypertension, hippocampal HO-1 level was significantly greater than that of age-matched SD rats (p < 0.05), but not different from 4-wk SHR. There was no difference in expression levels of hippocampal HO-2 between SHR and SD rats at different ages. Total enzymatic activity of hippocampal HO was significantly greater in 23-wk SHR than in age-matched SD rats or 4-wk SD/SHR (p < 0.01). Although hippocampal expression of nNOS protein was relatively unchanged, iNOS expression in 23-wk SHR was about fourfold lower than that in age-matched SD rats and 4-wk SD/SHR (p < 0.01). Total enzymatic activity of hippocampal NOS was significantly lower in 23-wk SHR than in age-matched SD rats or 4-wk SD/SHR (p < 0.01). Significantly suppressed Morris water maze performance was found in 23-wk SHR in comparison with age-matched SD rats. Because SHR has been used as a model of vascular dementia and hippocampus is essential for spatial learning and memory, understanding of altered HO/CO and NOS/NO systems in the hippocampus of adult SHR may shed light on the pathogenic development of memory deficits associated with vascular dementia.