Blocking NAD+/CD38/cADPR/Ca2+ pathway in sepsis prevents organ damage
Blocking NAD+/CD38/cADPR/Ca2+ pathway in sepsis prevents organ damage
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阻断脓毒症中的 NAD( )/CD38/cADPR/Ca(2 ) 通路可预防器官损伤。
DOI：
10.1016/j.jss.2015.11.029
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发表时间：
2016-04-01
影响因子：
2.2
通讯作者：
Ai, Yu-Hang
中科院分区：
文献类型：
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作者：
Peng, Qian-Yi;Ai, Mei-Lin;Ai, Yu-Hang
背景：尽管烟酰胺腺嘌呤二核苷酸(NAD(+))/CD38/环ADP核糖(CADPR)/钙离子信号通路在多种炎症过程中调节细胞内钙稳态并发挥作用，但其在脓毒症中的作用尚不清楚。本研究的目的是确定脓毒症时NAD(+)/CD38/cADPR/Ca~(2+)信号通路是否被激活，以及该通路的抑制剂8-BR-cADPR是否对脓毒症引起的器官损伤具有保护作用。材料和方法：雄性SD大鼠采用盲肠结扎穿孔(CLP)或假手术。分别于CLP术后0、6、12、24、48h检测脓毒症大鼠心、肝、肾组织中NAD(+)、cADPR、CD38及细胞内钙离子水平。将大鼠分为假手术组、CLP组和CLP+8-BR-cADPR组，对心、肝、肾进行苏木精-伊红染色，检测丙二醛和超氧化物歧化酶活性。结果：CLP术后6~24 h，心、肝、肾组织中NAD(+)、cADPR、CD38和细胞内钙离子水平均升高。8-BR-cADPR可抑制脓毒症大鼠脓毒症时细胞内钙离子的动员，减轻组织损伤，降低丙二醛水平，提高超氧化物歧化酶活性。结论：CLP大鼠脓毒症时NAD(+)/CD38/cADPR/钙信号通路被激活。用8-溴-cADPR阻断这一途径可保护心脏、肝脏和肾脏免受败血症所致的损伤。(C)2016 Elsevier Inc.保留所有权利。
Background: Although the nicotinamide adenine dinucleotide (NAD(+))/CD38/cyclic ADP ribose (cADPR)/Ca2+ signaling pathway has been shown to regulate intracellular calcium homeostasis and functions in multiple inflammatory processes, its role in sepsis remains unknown. The aim of this study was to determine whether the NAD(+)/CD38/cADPR/Ca2+ signaling pathway is activated during sepsis and whether an inhibitor of this pathway, 8-Br-cADPR, protects the organs from sepsis-induced damage.Materials and methods: Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) or sham laparotomies. NAD(+), cADPR, CD38, and intracellular Ca2+ levels were measured in the hearts, livers, and kidneys of septic rats at 0, 6, 12, 24, and 48 h after CLP surgery. Rats were also divided into sham, CLP, and CLP+8-Br-cADPR groups, and the hearts, livers, and kidneys were hematoxylineeosin-stained and assayed for malondialdehyde and superoxide dismutase activities.Results: NAD(+), cADPR, CD38, and intracellular Ca2+ levels increased in the hearts, livers, and kidneys of septic rats as early as 6-24 h after CLP surgery. Treatment with 8-Br-cADPR inhibited sepsis-induced intracellular Ca2+ mobilization, attenuated tissue injury, reduced malondialdehyde levels, and increased superoxide dismutase activity in septic rats.Conclusions: The NAD(+)/CD38/cADPR/Ca2+ signaling pathway was activated during sepsis in the CLP rat model. Blocking this pathway with 8-Br-cADPR protected hearts, livers, and kidneys from sepsis-induced damage. (C) 2016 Elsevier Inc. All rights reserved.