Downregulation of HMGB1 protects against the development of acute lung injury after severe acute pancreatitis

Downregulation of HMGB1 protects against the development of acute lung injury after severe acute pancreatitis
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DOI:
10.1016/j.imbio.2013.04.013
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发表时间:
2013-10-01
期刊:
影响因子:
2.8
通讯作者:
Guo, Ren-Xuan
Guo, Ren-Xuan
中科院分区:
医学4区
文献类型:
--
作者:
Luan, Zheng-Gang;Zhang, Xiao-Juan;Guo, Ren-Xuan

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目的:目的:探讨高迁移率族蛋白B1(HMGB 1)表达下调对重症急性胰腺炎(SAP)并发急性肺损伤(ALI)的影响及其对疾病严重程度的影响。胰管逆行注射5%牛磺胆酸钠诱发SAP。对照组仅接受假手术。在诱导SAP后收获肺和胰腺样品。检测肺组织中HMGB 1、基质金属蛋白酶-9(MMP-9)和细胞间粘附分子-1(ICAM-1)的蛋白水平。胰腺损伤的严重程度通过胰腺损伤的组织学评分、血清淀粉酶和胰腺含水量来确定。通过测定肺微血管通透性、肺髓过氧化物酶活性和丙二醛水平来评价肺损伤。结果发现,在pRNA-U6.1/Neo-HMGB 1处理的大鼠中,血清肿瘤坏死因子α(TNF-α)和白细胞介素-1 β与未处理的SAP或pRNA-U6.1/Neo.载体处理组大鼠(P
Objective: To examine the effect of downregulation of high mobility group box 1 (HMGB1) on severe acute pancreatitis (SAP) associated with acute lung injury (ALI), and its subsequent effect on disease severity.Methods: Wistar rats were given an IV injection of pRNA-U6.1/Neo-HMGB1, pRNA-U6.1/Neo-vector or saline before induction of SAP. Then, SAP was induced in rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. The control group received only a sham operation. Lung and pancreas samples were harvested after induction of SAP. The protein levels of HMGB1, matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) in lung tissue were investigated. The severity of pancreatic injury was determined by a histological score of pancreatic injury, serum amylase, and pancreatic water content. The lung injury was evaluated by measurement of pulmonary microvascular permeability, lung myeloperoxidase activity and malondialdehyde levels.Results: The results found that in pRNA-U6.1/Neo-HMGB1 treated rats, serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) levels were decreased and the severity of pancreatic tissue injury was less compared with either untreated SAP or pRNA-U6.1/Neo-vector treated rats (P