Chronic Treatment with a Water-Soluble Extract from the Culture Medium of Ganoderma lucidum Mycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia-Induced Injury of Type 2 Diabetic Mouse Brain.
Chronic Treatment with a Water-Soluble Extract from the Culture Medium of Ganoderma lucidum Mycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia-Induced Injury of Type 2 Diabetic Mouse Brain.
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DOI：
10.1155/2015/865986
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Hibino Y
中科院分区：
文献类型：
--
作者：
Xuan M;Okazaki M;Iwata N;Asano S;Kamiuchi S;Matsuzaki H;Sakamoto T;Miyano Y;Iizuka H;Hibino Y
已知2型糖尿病通过慢性高血糖和内脏肥胖增加全身氧化应激，并加重脑缺血损伤。在我们前期研究灵芝菌丝体培养液中具有抗氧化和神经保护作用的水溶性提取物(MAK)的基础上，本研究旨在评价MAK对2型糖尿病KKAy小鼠缺氧/缺血(H/I)诱导的细胞凋亡和坏死性下垂(程序性坏死)的预防作用。采用单侧颈总动脉结扎加低氧(8%O2，20 )和复氧相结合的方法诱导H/I。MAK(1 g/kg，P.O.)持续一周可显著减少缺氧/缺氧所致的神经功能障碍和脑梗塞体积，并在复氧24 小时进行评估。组织化学分析显示，MAK可显著抑制缺血半暗带内超氧化物歧化、神经细胞死亡和空泡化，同时伴有TUNEL或裂解caspase-3阳性细胞数量的减少。此外，MAK降低了受体相互作用蛋白激酶3mRNA和蛋白的表达，这是导致坏死性下垂的关键分子。这些结果表明，MAK具有抵抗细胞凋亡和坏死性细胞死亡的作用，并减轻了H/I诱导的2型糖尿病小鼠的脑缺血损伤。
Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (designed as MAK), which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis) induced by hypoxia/ischemia (H/I) in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2 for 20 min) and subsequent reoxygenation. Pretreatment with MAK (1 g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice.
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影响因子：
--
作者：
Matsuzaki H;Shimizu Y;Iwata N;Kamiuchi S;Suzuki F;Iizuka H;Hibino Y;Okazaki M
通讯作者：
Okazaki M
DOI：
10.1016/j.bbadis.2009.09.002
发表时间：
2010-01
影响因子：
6.2
作者：
Niizuma, Kuniyasu;Yoshioka, Hideyuki;Chen, Hai;Kim, Gab Seok;Jung, Joo Eun;Katsu, Masataka;Okami, Nobuya;Chan, Pak H.
通讯作者：
Chan, Pak H.
影响因子：
7.4
作者：
Li, PA;Liu, GJ;Siesjö, BK
通讯作者：
Siesjö, BK
影响因子：
8
作者：
Challa, Sreerupa;Chan, Francis Ka-Ming
通讯作者：
Chan, Francis Ka-Ming
影响因子：
64.5
作者：
Micheau, O;Tschopp, J
通讯作者：
Tschopp, J