[1]陈伟,任大斌,郑平,等.与缺氧诱导因子-1α调控相关的缝隙连接43蛋白磷酸化参与脑缺血再灌注损伤的机制[J].临床神经外科杂志,2019,16(2):142-146.[doi:10.3969/j.issn.1672-7770.2019.02.010]
 CHEN Wei,REN Da-bin,ZHENG Ping,et al.Phosphorylation of Cx43 regulated by HIF-1α in cerebral ischemia-repufusion injury[J].Journal of Clinical Neurosurgery,2019,16(2):142-146.[doi:10.3969/j.issn.1672-7770.2019.02.010]
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与缺氧诱导因子-1α调控相关的缝隙连接43蛋白磷酸化参与脑缺血再灌注损伤的机制 ()
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《临床神经外科杂志》[ISSN:1672-7770/CN:32-1727/R]

卷:
16
期数:
2019年第2期
页码:
142-146
栏目:
论著
出版日期:
2019-04-17

文章信息/Info

Title:
Phosphorylation of Cx43 regulated by HIF-1α in cerebral ischemia-repufusion injury
作者:
陈伟任大斌郑平童武松郭义君吴晨星赵麟刘宁冯九庚段剑邹树峰
201299 上海,上海健康医学院附属上海浦东新区人民医院神经外科(陈伟,任大斌,郑平,童武松,郭义君,吴晨星);南京医科大学第一附属医院神经外科(赵麟,刘宁);南昌大学第一附属医院神经外科(陈伟,冯九庚,段剑,邹树峰)
Author(s):
CHEN Wei REN Da-bin ZHENG Ping et al.
Department of Neurosurgery, the Peopl's Hospital of Shanghai Pudong New Area Affiliated to Shanghai University of Medicine and Health Sciences,Shanghai 201299, China
关键词:
缝隙连接43缺氧诱导因子1α炎性因子脑水肿脑缺血再灌注损伤
Keywords:
connexin43HIF-1αinflammatory factorcerebral edemacerebral ischemi repufusion injury
分类号:
R651
DOI:
10.3969/j.issn.1672-7770.2019.02.010
文献标志码:
A
摘要:
【摘要】目的 观察缺氧诱导因子-1α(HIF-1α)所致的缝隙连接43蛋白(connexin43,Cx43)磷酸化对脑缺血再灌注(cerebral ischemia and reperfusion,I/R)损伤的相关机制。方法选取成年SD雄性大鼠100只,随机分为4部分5组,每组20只:(1)假手术组,仅暴露双侧颈总动脉而不予夹闭;(2)治疗组,I/R后立即腹腔注入HIF-1α特异抑制剂2甲氧基本雌二醇(2ME2) 15 mg/kg,实验时间设定为I/R后4 h及8 h;(3)溶媒组,以溶媒二甲基亚枫(DMSO)替代2ME2;(4) I/R损伤组,I/R形成后不给予处理,(3)和(4)实验时间均设定为I/R后8 h。每组取10只动物行脑组织含水量测定;另10只动物在预定时间取海马区域皮质标本,采用免疫印迹法(Western blot,WB)检测磷酸化Cx43(p-Cx43)、Bcl-2、Bax、Caspases-3的表达水平,并用酶联免疫法(ELISA)检测海马皮质组织中炎性因子的含量,用干蒸法测定脑水肿的程度。结果采用2ME2干预的治疗组大鼠各时间段的脑含水量及海马皮质组织的p-Cx43、炎性因子、Cx40、凋亡促进因子Bax、Caspases-3表达水平均明显降低(均P<0.05),凋亡抑制因子Bcl-2表达水平明显升高(P<0.05)。结论通过特异性抑制HIF1α的形成,可降低神经细胞Cx43磷酸化的形成,明显降低炎性因子的分泌;并可对脑I/R所致的损伤产生缓解作用;对脑缺血疾病在超急性期的治疗有着重大的意义。
Abstract:
Abstract: ObjectiveTo investigate the effect of inhibition of HIF1α to alleviate the phosphorylation of Cx43 in the acute phase of cerebral ischemiarepufusion(I/R) injury. MethodsOne hundred Sprague-Dawley rats at 4 months age,weight at 300500 g were randomly divided into 4 sections and 5 groups: sham operation, treament group(I/R4,8 hour+2ME2), vehicle(I/R 8 hour+ DMSO) and injury group(I/R 8 hour). Cerebral ischemiarepufusion injury model were established with clip bilateral ICA, and HIF-1αinhibitor 2ME2 was injected into peritoneal cavity. Half of rats were measured for cerebral water content by Hatashita wet-weight method.Another half rats were sacrificed for investigating the level of total-Cx43, phosphoylated Cx43, Bcl-2, Bax and Caspases-3 by western blot, TNF-α, IL-1β and IL-6 by Elisa kit. Result Unlike static total-Cx43, brain water content, phosphoylated Cx43, Bax, Caspases-3, and IL-1β, IL-6, TNF-α in each treatment group and sham group were significantly lower than in other groups. Bcl-2 by WB showed the opposite result to the above. ConclusionInhibition of HIF-1αcan down-regulate the level of phosphoylation of Cx43 and apoptosis factors.Further more, the level of IL-1, IL-6 and TNF-α were reduced. Simultaneously,these alterations can protect the form and function of brain after cerebral ischemia-repufusion injury.
更新日期/Last Update: 2019-04-17