Penehyclidine hydrochloride attenuates the cerebral injury in a rat model of cardiopulmonary bypass
Penehyclidine hydrochloride attenuates the cerebral injury in a rat model of cardiopulmonary bypass
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DOI：
10.1139/cjpp-2012-0329
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发表时间：
2013-07-01
影响因子：
2.1
通讯作者：
Diao, Yu-gang
中科院分区：
文献类型：
--
作者：
Cao, Hui-juan;Sun, Ying-jie;Diao, Yu-gang
本研究探讨了盐酸戊乙奎醚(PHC)在体外循环(CPB)后神经炎性反应和脑细胞凋亡过程中对调节介质的影响。将48只大鼠随机分为4组：假手术组、赋形剂组、低剂量PHC组(0.6 mg·kg~(-1))和高剂量PHC组(2.0 mg·kg~(-1))。后3组均行体外循环。用双抗体夹心法检测血浆神经元特异性烯醇化酶和S-100B水平。实时定量聚合酶链式反应和免疫印迹法检测脑组织中基质金属蛋白酶-9(MMP9)、白介素10(IL-10)、半胱氨酸天冬氨酸氨基转移酶-3(caspase-3)、bcl2和p38的表达水平。在电子显微镜下观察海马区组织的超微结构。PHC可减轻CPB后血浆NSE和S-100B的升高。与假手术组相比，赋形剂组基质金属蛋白酶-9、裂解半胱氨酸天冬氨酸蛋白酶-3和磷酸化p38的表达显著增加，并随着PHC剂量的增加逐渐减弱。溶媒组IL-10和Bcl-2的表达明显低于假手术组，并随着PHC剂量的增加逐渐恢复。PHC可减轻CPB后脑损伤的组织病理学改变。PHC可能通过减少p38和caspase-3的激活，有利地调节CPB后的炎症反应和减少神经元损伤的标志物。
This study investigated the effect of penehyclidine hydrochloride (PHC) on regulatory mediators during the neuroinflammatory response and cerebral cell apoptosis following cardiopulmonary bypass (CPB). Forty-eight rats were randomly divided among 4 groups as follows: sham-operation, vehicle, low-dose PHC (0.6 mg.(kg body mass)(-1)), and high-dose PHC (2.0 mg.(kg body mass)(-1)). CPB was performed in the latter 3 groups. The plasma levels of neuron specific enolase (NSE) and S-100B were tested with ELISA. Real-time PCR and Western blotting were used to evaluate the expression levels of matrix metalloproteinase-9 (MMP-9), IL-10, caspase-3, Bcl-2, and p38 in brain tissue. The ultrastructure of hippocampus tissue was examined under an electron microscope. PHC attenuated the increase of plasma NSE and S-100B following CPB. MMP-9, cleaved caspase-3, and phosphorylated p38 expression were substantially increased in the vehicle group compared with the sham-operation group and gradually diminished with increasing doses of PHC. IL-10 and Bcl-2 expression were markedly lower in the vehicle group than in the sham-operation group and gradually recovered with increasing doses of PHC. PHC attenuated the histopathological changes of cerebral injury following CPB. PHC favorably regulates the inflammatory response and reduces markers of neuronal injury following CPB, potentially by reducing p38 and caspase-3 activation.