Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats.
Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats.
复制标题
格列本脲在改善大鼠心脏骤停窒息后的存活率和神经系统结果方面与目标温度管理相当
DOI：
10.1161/jaha.116.003465
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发表时间：
2016-07-13
影响因子：
5.4
通讯作者：
Pan S
中科院分区：
文献类型：
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作者：
Huang K;Wang Z;Gu Y;Hu Y;Ji Z;Wang S;Lin Z;Li X;Xie Z;Pan S
我们之前已经证明，格列本脲（GBC），一种磺酰脲类受体1-瞬时受体电位M4（SUR1-TRPM 4）通道抑制剂，可改善窒息性心脏骤停和心肺复苏（ACA/CPR）后的生存率和神经系统结局。在这里，我们进一步比较GBC与目标温度管理（TTM）的疗效，并确定GBC的疗效是否受TTM的影响。接受10分钟ACA/CPR的雄性Sprague-道利大鼠（n = 213）在恢复自主循环（ROSC）后随机分为4组：常温对照组（NT）、GBC、TTM和TTM + GBC。观察存活率、神经功能缺损评分、组织学损伤以及SUR1和TRPM4的表达。NT组的7天生存率为34.4%（11/32），GBC组为65%（13/20），TTM组为50%（10/20），TTM + GBC组为70%（14/20）。在ROSC后24、48和72小时和7天，接受GBC、TTM单独或组合的大鼠显示出比NT对照更少的神经功能缺损。此外，TTM或GBC改善海马CA1区神经元变性和胶质细胞活化的效果相似，而它们的组合有更好的效果的趋势。SUR1-TRPM 4异二聚体的亚基在ACA/CPR后均强烈上调，并在多种类型的脑细胞中表达，但部分被TTM抑制。 GBC在改善ACA/CPR后的生存率和神经结局方面与TTM相当。当GBC与TTM沿着给药时，倾向于实现较少的组织学损伤。
We previously have shown that glibenclamide (GBC), a sulfonylurea receptor 1–transient receptor potential M4 (SUR1‐TRPM4) channel inhibitor, improves survival and neurological outcome after asphyxial cardiac arrest and cardiopulmonary resuscitation (ACA/CPR). Here, we further compare the efficacy of GBC with target temperature management (TTM) and determine whether the efficacy of GBC is affected by TTM. Male Sprague‐Dawley rats (n=213) subjected to 10‐minute ACA/CPR were randomized to 4 groups after return of spontaneous circulation (ROSC): normothermia control (NT); GBC; TTM; and TTM+GBC. Survival, neurodeficit scores, histological injury, as well as the expressions of SUR1 and TRPM4 were evaluated. The 7‐day survival rate was 34.4% (11 of 32) in the NT group, 65% (13 of 20) in the GBC group, 50% (10 of 20) in the TTM group, and 70% (14 of 20) in the TTM+GBC group. Rats that received either GBC, TTM alone, or in combination showed less neurological deficit than NT control at 24, 48, and 72 hours and 7 days after ROSC. Moreover, TTM or GBC ameliorated neuronal degeneration and glial activation in the hippocampal CA1 region with similar efficacy, whereas the combination of them had a trend toward better effect. The subunits of SUR1‐TRPM4 heterodimers were both strongly upregulated after ACA/CPR and expressed in multiple types of brain cells, but partly suppressed by TTM. GBC is comparable to TTM in improving survival and neurological outcome after ACA/CPR. When GBC is given along with TTM, less histological injury tended to be achieved.