Thrombin action on astrocytes in the hindbrain of the rat disrupts glycemic and respiratory control.
Thrombin action on astrocytes in the hindbrain of the rat disrupts glycemic and respiratory control.
复制标题
凝血酶对大鼠后脑星形胶质细胞的作用会破坏血糖和呼吸控制。
DOI：
10.1152/ajpregu.00033.2020
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Hermann,GerlindaE
中科院分区：
文献类型：
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作者：
Rogers,RichardC;Hasser,EileenM;Hermann,GerlindaE
严重创伤可产生以分解代谢和高血糖为特征的损伤后“代谢性自毁”。高血糖的严重程度与创伤后发病率和死亡率高度相关。虽然没有任何机制被认为是严重创伤与自主控制代谢的损失，创伤性损伤引起其他自主功能的失败，特别是，胃淤滞和溃疡（“库欣溃疡”），这与凝血酶的产生有关。我们以前的研究表明，位于孤束核（NST）的星形胶质细胞上的蛋白酶激活受体（PAR 1;“凝血酶受体”）可以调节胃控制回路神经元，导致胃停滞。后脑星形胶质细胞也被认为是低葡萄糖或葡萄糖利用率的重要检测器。当被激活时，这些星形胶质细胞与后脑儿茶酚胺神经元通信，进而触发反调节反应（CRR）。凝血酶对扰乱后脑胃肠道控制的作用与启动CRR以增加对严重低血糖反应的后脑回路之间可能存在趋同性。我们的研究结果表明，凝血酶在NST内通过星形胶质细胞依赖性机制起作用以增加NST。嘌呤能神经胶质传递通路的阻断中断了凝血酶增加神经元凋亡的作用。我们的研究还表明，凝血酶，在NST的作用，产生了一个快速的，戏剧性的，并可能致命的呼吸节律抑制，这也是一个功能的嘌呤神经胶质传递。这些结果表明，创伤性损伤和自主神经调节的普遍崩溃之间的关键联系涉及凝血酶对星形胶质细胞的作用。
Severe trauma can produce a postinjury “metabolic self-destruction” characterized by catabolic metabolism and hyperglycemia. The severity of the hyperglycemia is highly correlated with posttrauma morbidity and mortality. Although no mechanism has been posited to connect severe trauma with a loss of autonomic control over metabolism, traumatic injury causes other failures of autonomic function, notably, gastric stasis and ulceration (“Cushing’s ulcer”), which has been connected with the generation of thrombin. Our previous studies established that proteinase-activated receptors (PAR1; “thrombin receptors”) located on astrocytes in the autonomically critical nucleus of the solitary tract (NST) can modulate gastric control circuit neurons to cause gastric stasis. Hindbrain astrocytes have also been implicated as important detectors of low glucose or glucose utilization. When activated, these astrocytes communicate with hindbrain catecholamine neurons that, in turn, trigger counterregulatory responses (CRR). There may be a convergence between the effects of thrombin to derange hindbrain gastrointestinal control and the hindbrain circuitry that initiates CRR to increase glycemia in reaction to critical hypoglycemia. Our results suggest that thrombin acts within the NST to increase glycemia through an astrocyte-dependent mechanism. Blockade of purinergic gliotransmission pathways interrupted the effect of thrombin to increase glycemia. Our studies also revealed that thrombin, acting in the NST, produced a rapid, dramatic, and potentially lethal suppression of respiratory rhythm that was also a function of purinergic gliotransmission. These results suggest that the critical connection between traumatic injury and a general collapse of autonomic regulation involves thrombin action on astrocytes.