Neutralizing IL-6 reduces heart injury by decreasing nerve growth factor precursor in the heart and hypothalamus during rat cardiopulmonary bypass
Neutralizing IL-6 reduces heart injury by decreasing nerve growth factor precursor in the heart and hypothalamus during rat cardiopulmonary bypass
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中和 IL-6 通过减少大鼠体外循环期间心脏和下丘脑中的神经生长因子前体来减少心脏损伤
DOI：
10.1016/j.lfs.2017.04.007
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发表时间：
2017-06-01
期刊：
影响因子：
6.1
通讯作者：
Yu, Tian
中科院分区：
文献类型：
--
作者：
Cheng, Chi;Xu, Jun-mei;Yu, Tian
目的：探讨体外循环（CPB）过程中神经生长因子前体（proNGF）表达的变化及中和白细胞介素-6 （IL-6）是否对心脏有益。主要方法：选取30例CPB患者，检测其血清proNGF和肌钙蛋白i （TNI）水平。将大鼠分为CPB组、CPB合并心脏缺血再灌注（IR）组和对照组。比较cpb前和cpb后N-N区间标准差（SDNN）。CPB结束时，测定心脏和下丘脑神经肽Y （NPY）、乙酰胆碱酯酶、细胞凋亡和proNGF蛋白表达。另一组接受CPB的大鼠分为两组：IL-6抗体抗IL-6组和磷酸盐缓冲液对照组。CPB结束时，检测血清hs-肌钙蛋白-t和心脏半胱天冬酶3、9。检测心脏和下丘脑的NPY和proNGF。关键发现：CPB患者血清proNGF升高，且浓度与TNI呈正相关。CPB对大鼠的心脏自主神经功能有干扰作用。CPB组心脏和下丘脑的凋亡细胞和proNGF水平均高于对照组。中和IL-6可通过减少proNGF和细胞凋亡来减轻心脏损伤。意义：CPB诱导心脏和下丘脑proNGF的改变。抑制炎症可减轻CPB大鼠的心肌凋亡和自主神经功能障碍，这可能部分是由于心脏和下丘脑中proNGF的调节。(C) 2017年Elsevier Inc.出版。
Aims: To investigate whether the expression of nerve growth factor precursor (proNGF) changes during cardiopulmonary bypass (CPB) and whether neutralizing interleukin-6 (IL-6) during CPB has cardiac benefits.Main methods: Thirty patients undergoing CPB were recruited and their serum proNGF and troponin-I (TNI) were detected. In addition, rats were divided into three groups: CPB group, CPB with cardiac ischemia-reperfusion (IR) group, and a control group. The pre-CPB standard deviation of N-N intervals (SDNN) and post-CPB SDNN were compared. At the end of CPB, nerve peptide Y (NPY), acetylcholinesterase, cell apoptosis, and proNGF protein expression were measured in the heart and hypothalamus. Another rat cohort undergoing CPB was divided into two groups: an anti-IL-6 group with IL-6 antibody and a control group with phosphate buffer solution. At the end of CPB, serum hs-troponin-T and cardiac caspases 3 and 9 were detected. NPY and proNGF in the heart and hypothalamus were detected.Key findings: In patients, serum proNGF increased during CPB, and the concentration was positively correlated with TNI. In rats, cardiac autonomic nervous function was disturbed during CPB. More apoptotic cells and higher levels of proNGF were found in the heart and hypothalamus in the CPB groups than in the control groups. Neutralizing IL-6 was beneficial to lower cardiac injury by decreasing proNGF and apoptosis.Significance: CPB induced changes in proNGF in the heart and hypothalamus. Suppressing inflammation attenuated myocardial apoptosis and autonomic nerve function disturbance in CPB rats, likely due in part to regulation of proNGF in the heart and hypothalamus. (C) 2017 Published by Elsevier Inc.