αII-血影蛋白降解产物作为低温循环停止犬模型中脑损伤严重程度的新型标志物。
Alpha II-spectrin breakdown products serve as novel markers of brain injury severity in a canine model of hypothermic circulatory arrest.
作者信息
Weiss Eric S, Wang Kevin K W, Allen Jeremiah G, Blue Mary E, Nwakanma Lois U, Liu Ming Cheng, Lange Mary S, Berrong Jennifer, Wilson Mary Ann, Gott Vincent L, Troncoso Juan C, Hayes Ronald L, Johnston Michael V, Baumgartner William A
机构信息
Division of Cardiac Surgery, Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
出版信息
Ann Thorac Surg. 2009 Aug;88(2):543-50. doi: 10.1016/j.athoracsur.2009.04.016.
BACKGROUND
The development of specific biomarkers to aid in the diagnosis and prognosis of neuronal injury is of paramount importance in cardiac surgery. Alpha II-spectrin is a structural protein abundant in neurons of the central nervous system and cleaved into signature fragments by proteases involved in necrotic and apoptotic cell death. We measured cerebrospinal fluid alpha II-spectrin breakdown products (alphaII-SBDPs) in a canine model of hypothermic circulatory arrest (HCA) and cardiopulmonary bypass.
METHODS
Canine subjects were exposed to either 1 hour of HCA (n = 8; mean lowest tympanic temperature 18.0 +/- 1.2 degrees C) or standard cardiopulmonary bypass (n = 7). Cerebrospinal fluid samples were collected before treatment and 8 and 24 hours after treatment. Using polyacrylamide gel electrophoresis and immunoblotting, SBDPs were isolated and compared between groups using computer-assisted densitometric scanning. Necrotic versus apoptotic cell death was indexed by measuring calpain and caspase-3 cleaved alphaII-SBDPs (SBDP 145+150 and SBDP 120, respectively).
RESULTS
Animals undergoing HCA demonstrated mild patterns of histologic cellular injury and clinically detectable neurologic dysfunction. Calpain-produced alphaII-SBDPs (150 kDa+145 kDa bands-necrosis) 8 hours after HCA were significantly increased (p = 0.02) as compared with levels before HCA, and remained elevated at 24 hours after HCA. In contrast, caspase-3 alphaII-SBDP (120 kDa band-apoptosis) was not significantly increased. Animals receiving cardiopulmonary bypass did not demonstrate clinical or histologic evidence of injury, with no increases in necrotic or apoptotic cellular markers.
CONCLUSIONS
We report the use of alphaII-SBDPs as markers of neurologic injury after cardiac surgery. Our analysis demonstrates that calpain- and caspase-produced alphaII-SBDPs may be an important and novel marker of neurologic injury after HCA.
背景
开发有助于心脏手术中神经元损伤诊断和预后评估的特定生物标志物至关重要。αII - 血影蛋白是一种在中枢神经系统神经元中丰富的结构蛋白，可被参与坏死和凋亡性细胞死亡的蛋白酶切割成标志性片段。我们在低温循环骤停（HCA）和体外循环的犬模型中测量了脑脊液αII - 血影蛋白降解产物（αII - SBDPs）。
方法
犬受试者接受1小时的HCA（n = 8；平均最低鼓膜温度18.0±1.2℃）或标准体外循环（n = 7）。在治疗前以及治疗后8小时和24小时收集脑脊液样本。使用聚丙烯酰胺凝胶电泳和免疫印迹法分离SBDPs，并通过计算机辅助光密度扫描比较组间差异。通过测量钙蛋白酶和半胱天冬酶 - 3切割的αII - SBDPs（分别为SBDP 145 + 150和SBDP 120）来确定坏死与凋亡性细胞死亡。
结果
接受HCA的动物表现出轻度的组织学细胞损伤模式和临床可检测到的神经功能障碍。与HCA前水平相比，HCA后8小时钙蛋白酶产生的αII - SBDPs（150 kDa + 145 kDa条带 - 坏死）显著增加（p = 0.02），并在HCA后24小时保持升高。相比之下，半胱天冬酶 - 3αII - SBDP（120 kDa条带 - 凋亡）没有显著增加。接受体外循环的动物没有表现出损伤的临床或组织学证据，坏死或凋亡细胞标志物也没有增加。
结论
我们报告了使用αII - SBDPs作为心脏手术后神经损伤的标志物。我们的分析表明，钙蛋白酶和半胱天冬酶产生的αII - SBDPs可能是HCA后神经损伤的一种重要且新颖的标志物。
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