Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice.
Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice.
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硫化氢可减轻小鼠中脑内施用的同型半胱氨酸诱导的神经变性和神经血管功能障碍。
DOI：
10.1016/j.neuroscience.2013.07.051
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发表时间：
2013-11-12
期刊：
影响因子：
3.3
通讯作者：
Tyagi N
中科院分区：
文献类型：
--
作者：
Kamat PK;Kalani A;Givvimani S;Sathnur PB;Tyagi SC;Tyagi N
高水平的同型半胱氨酸 (Hcy)，称为高同型半胱氨酸血症 (HHcy)，与神经血管疾病相关。 H2S是Hcy的代谢产物，具有有效的抗氧化和抗炎活性；然而，H2S 在 Hcy (IC) 诱导的小鼠神经变性和神经血管功能障碍中的作用尚未被探索。因此，本研究旨在探讨H2S对Hcy诱导的神经变性和神经血管功能障碍的神经保护作用。为了检验这一假设，我们采用了 8-10 周龄的野生型 (WT) 雄性，WT+ 人工脑脊液 (aCSF)、WT+ Hcy (0.5μmol/μl) 脑内注射（I.C.，仅在 NaHS 治疗前一次）、WT+Hcy + NaHS（硫化氢钠，H2S 的前体，30 μmol/kg，身体） 重量）。 Hcy (IC) 注射后 7 天，每天一次腹膜内 (I.P.) 注射 NaHS。与对照组和 aCSF 治疗组相比，Hcy 治疗显着增加了 MDA、亚硝酸盐水平、乙酰胆碱酶活性、TNFα、IL1β、GFAP、iNOS、eNOS 并降低了谷胱甘肽水平，表明氧化亚硝化应激和神经炎症。此外，NSE、S100B 表达增加和 (PSD95、SAP97) 突触蛋白表达减少表明神经退行性变。 Hcy 治疗小鼠的脑切片显示皮质区域和脑室周围细胞受损。 TUNEL 阳性细胞和 Fluro Jade-C 染色表明细胞凋亡和神经变性。 Hcy治疗组MMP9、MMP2表达增加，TIMP-1、TIMP-2、紧密连接蛋白（ZO1、Occuldin）表达减少，提示神经血管重塑。有趣的是，NaHS 治疗显着减弱 Hcy 诱导的氧化应激、记忆缺陷、神经变性、神经炎症和脑血管重塑。结果表明，H2S 可有效防止神经变性和神经血管功能障碍。
High levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy) are associated with neurovascular diseases. H2S, a metabolite of Hcy, has a potent anti-oxidant and anti-inflammatory activity; however, the effect of H2S has not been explored in Hcy (IC) induced neurodegeneration and neurovascular dysfunction in mice. Therefore, the present study was designed to explore the neuroprotective role of H2S on Hcy induced neurodegeneration and neurovascular dysfunction. To test this hypothesis we employed wild type (WT) males ages 8–10 weeks, WT+ artificial cerebrospinal fluid (aCSF), WT+ Hcy (0.5μmol/μl) intracerebral injection (I.C., one time only prior to NaHS treatment), WT+Hcy +NaHS (sodium hydrogen sulfide, precursor of H2S, 30 μmol/kg, body weight). NaHS was injected intra-peritoneally (I.P.) once daily for the period of 7 days after the Hcy (IC) injection. Hcy treatment significantly increased MDA, nitrite level, acetylcholinestrase activity, TNFα, IL1β, GFAP, iNOS, eNOS and decreased glutathione level indicating oxidative-nitrosative stress and neuroinflammation as compared to control and aCSF treated groups. Further, increased expression of NSE, S100B and decreased expression of (PSD95, SAP97) synaptic protein indicated neurodegeneration. Brain sections of Hcy treated mice showed damage in the cortical area and periventricular cells. TUNEL positive cells and Fluro Jade-C staining indicated apoptosis and neurodegeneration. The increased expression of MMP9, MMP2 and decreased expression of TIMP-1, TIMP-2, tight junction proteins (ZO1, Occuldin) in Hcy treated group indicate neurovascular remodeling. Interestingly, NaHS treatment significantly attenuated Hcy induced oxidative stress, memory deficit, neurodegeneration, neuroinflammation and cerebrovascular remodeling. The results indicate that H2S is effective in providing protection against neurodegeneration and neurovascular dysfunction.
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影响因子：
37.8
作者：
Kanani, PM;Sinkey, CA;Haynes, WG
通讯作者：
Haynes, WG
影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR
DOI：
10.1097/00004647-199905000-00003
发表时间：
1999-05-01
影响因子：
6.3
作者：
Fujimura, M;Morita-Fujimura, Y;Chan, PH
通讯作者：
Chan, PH
影响因子：
37.8
作者：
Dollery, CM;Humphries, SE;McEwan, JR
通讯作者：
McEwan, JR
影响因子：
5
作者：
Kamat, Pradeep Kumar;Tota, Santoshkumar;Nath, Chandishwar
通讯作者：
Nath, Chandishwar