β-肾上腺素能受体抑制作用影响创伤性脑损伤后大脑葡萄糖代谢、运动性能和炎症反应。
β-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, and inflammatory response after traumatic brain injury.
机构信息
Department of Surgery, Cedars-Sinai Medical Center, University of Southern California, Los Angeles, CA, USA.
出版信息
J Trauma Acute Care Surg. 2012 Jul;73(1):33-40. doi: 10.1097/TA.0b013e31825a769b.
BACKGROUND
The purpose of this study was to evaluate how β-adrenergic receptor inhibition after traumatic brain injury (TBI) alters changes in early cerebral glucose metabolism and motor performance, as well as cerebral cytokine and heat shock protein (HSP) expression.
METHODS
Mouse cerebral glucose metabolism was measured by microPET fluorodeoxyglucose uptake and converted into standardized uptake values (SUV). Four groups of C57/Bl6 mice (wild type [WT]) were initially evaluated: sham or TBI, followed by tail vein injection of either saline or a nonselective β-adrenergic receptor inhibitor (propranolol, 4 mg/kg). Then motor performance, cerebral cytokine, and HSP70 expression were studied at 12 hours and 24 hours after sham injury or TBI in WT mice treated with saline or propranolol and in β1-adrenergic/β2-adrenergic receptor knockout (BARKO) mice treated with saline.
RESULTS
Cerebral glucose metabolism was significantly reduced after TBI (mean SUV TBI, 1.63 vs. sham 1.97, p < 0.01) and propranolol attenuated this reduction (mean SUV propranolol, 1.89 vs. saline 1.63, p < 0.01). Both propranolol and BARKO reduced motor deficits at 24 hours after injury, but only BARKO had an effect at 12 hours after injury. TBI WT mice treated with saline performed worse than propranolol mice at 24 hours after injury on rotarod (23 vs. 44 seconds, p < 0.01) and rearing (130 vs. 338 events, p = 0.01) results. At 24 hours after injury, sham BARKO and TBI BARKO mice were similar on rotarod (21 vs. 19 seconds, p = 0.53), ambulatory testing (2,891 vs. 2,274 events, p = 0.14), and rearing (129 vs. 64 events, p = 0.09) results. Interleukin 1β expression was affected by BARKO and propranolol after TBI; attenuation of interleukin 6 and increased HSP70 expression were noted only with BARKO.
CONCLUSION
β-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, as well as cerebral cytokine and HSP expression after TBI.
背景
本研究旨在评估创伤性脑损伤（TBI）后β-肾上腺素能受体抑制如何改变早期脑葡萄糖代谢和运动表现的变化，以及脑细胞因子和热休克蛋白（HSP）的表达。
方法
通过 microPET 氟脱氧葡萄糖摄取测量小鼠脑葡萄糖代谢，并将其转换为标准化摄取值（SUV）。最初评估了 4 组 C57/Bl6 小鼠（野生型[WT]）：假手术或 TBI，然后尾静脉注射生理盐水或非选择性β-肾上腺素能受体抑制剂（普萘洛尔，4mg/kg）。然后，在接受生理盐水或普萘洛尔治疗的 WT 小鼠以及接受生理盐水治疗的β1-肾上腺素能/β2-肾上腺素能受体敲除（BARKO）小鼠中，研究了假伤或 TBI 后 12 小时和 24 小时的运动表现、脑细胞因子和 HSP70 表达。
结果
TBI 后脑葡萄糖代谢明显降低（TBI 平均 SUV，1.63 与假手术 1.97，p<0.01），普萘洛尔减轻了这种降低（普萘洛尔平均 SUV，1.89 与生理盐水 1.63，p<0.01）。普萘洛尔和 BARKO 均在损伤后 24 小时降低运动缺陷，但仅 BARKO 在损伤后 12 小时有作用。接受生理盐水治疗的 TBI WT 小鼠在损伤后 24 小时的旋转棒（23 与 44 秒，p<0.01）和竖起（130 与 338 次，p=0.01）测试中的表现不如接受普萘洛尔治疗的小鼠。在损伤后 24 小时，假手术 BARKO 和 TBI BARKO 小鼠在旋转棒（21 与 19 秒，p=0.53）、活动测试（2891 与 2274 次，p=0.14）和竖起（129 与 64 次，p=0.09）测试中的结果相似。白细胞介素 1β的表达受 BARKO 和 TBI 后普萘洛尔的影响；白细胞介素 6 的衰减和 HSP70 表达的增加仅在 BARKO 中观察到。
结论
β-肾上腺素能受体抑制影响 TBI 后脑葡萄糖代谢、运动表现以及脑细胞因子和 HSP 的表达。
Zotero 插件