Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus.
Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus.
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DOI：
10.1186/1742-2094-9-69
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发表时间：
2012-04-18
影响因子：
9.3
通讯作者：
Luo B
中科院分区：
文献类型：
--
作者：
Chu K;Yin B;Wang J;Peng G;Liang H;Xu Z;Du Y;Fang M;Xia Q;Luo B
神经炎症在脑缺血再灌注损伤中起重要作用。P2 X7受体（P2 X7 R）已被报道参与许多中枢神经系统疾病的炎症反应。然而，P2 X7受体在短暂性全脑I/R损伤中的作用仍不清楚。本研究旨在观察抑制P2 X7 R对大鼠短暂性全脑I/R损伤的影响，探讨P2 X7 R与短暂性全脑I/R损伤后神经炎症的关系。用四血管阻断法（4-VO）建立大鼠短暂性全脑缺血再灌注模型，分别注入P2 X7受体拮抗剂亮蓝G（BBG）、腺苷-5 ′-三磷酸-2 ′，3 ′-二醛（OxATP）或A-438079后，立即观察缺血再灌注对大鼠脑缺血再灌注损伤的影响。计算存活率，使用H & E染色观察海马CA 1区的神经元死亡，并通过脱氧核苷酸转移酶介导的UTP缺口末端标记（TUNEL）观察DNA切割。采用Morris水迷宫检测大鼠行为学改变，RT-PCR和免疫组织化学染色检测IL-1β、TNF-α和IL-6的表达，并鉴定活化的小胶质细胞和星形胶质细胞。P2 X7 R拮抗剂以剂量依赖性方式保护短暂性全脑I/R损伤。高剂量的BBG（10 μg）和A-0438079（3 μg）以及低剂量的OxATP（1 μg）显著增加了存活率，减少了I/R诱导的学习记忆缺陷，并减少了I/R诱导的海马神经元死亡、DNA裂解、胶质细胞活化和炎性细胞因子过表达。我们的研究表明，抑制P2 X7 Rs通过减少I/R诱导的炎症反应来保护短暂性全脑I/R损伤，这表明抑制P2 X7 Rs可能是临床治疗短暂性全脑I/R损伤的有希望的治疗策略。
Neuroinflammation plays an important role in cerebral ischemia/reperfusion (I/R) injury. The P2X7 receptor (P2X7R) has been reported to be involved in the inflammatory response of many central nervous system diseases. However, the role of P2X7Rs in transient global cerebral I/R injury remains unclear. The purpose of this study is to determine the effects of inhibiting the P2X7R in a rat model of transient global cerebral I/R injury, and then to explore the association between the P2X7R and neuroinflammation after transient global cerebral I/R injury. Immediately after infusion with the P2X7R antagonists Brilliant blue G (BBG), adenosine 5′-triphosphate-2′,3′-dialdehyde (OxATP) or A-438079, 20 minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO) method in rats. Survival rate was calculated, neuronal death in the hippocampal CA1 region was observed using H & E staining, and DNA cleavage was observed by deoxynucleotidyl transferase-mediated UTP nick end labeling TUNEL). In addition, behavioral deficits were measured using the Morris water maze, and RT-PCR and immunohistochemical staining were performed to measure the expression of IL-1β, TNF-α and IL-6, and to identify activated microglia and astrocytes. The P2X7R antagonists protected against transient global cerebral I/R injury in a dosage-dependent manner. A high dosage of BBG (10 μg) and A-0438079 (3 μg), and a low dosage of OxATP (1 μg) significantly increased survival rates, reduced I/R-induced learning memory deficit, and reduced I/R-induced neuronal death, DNA cleavage, and glial activation and inflammatory cytokine overexpression in the hippocampus. Our study indicates that inhibiting P2X7Rs protects against transient global cerebral I/R injury by reducing the I/R-induced inflammatory response, which suggests inhibition of P2X7Rs may be a promising therapeutic strategy for clinical treatment of transient global cerebral I/R injury.
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DOI：
10.1097/01.wcb.0000048519.34839.97
发表时间：
2003-03-01
影响因子：
6.3
作者：
Le Feuvre, RA;Brough, D;Rothwell, NJ
通讯作者：
Rothwell, NJ
影响因子：
2.5
作者：
Craighead, MW;Middlehurst, KML;Rothwell, NJ
通讯作者：
Rothwell, NJ
影响因子：
6.2
作者：
Domercq, Maria;Perez-Samartin, Alberto;Matute, Carlos
通讯作者：
Matute, Carlos
影响因子：
6.2
作者：
Kukley, M;Barden, JA;Jabs, R
通讯作者：
Jabs, R
影响因子：
7.3
作者：
Hibell, AD;Kidd, EJ;Michel, AD
通讯作者：
Michel, AD