Emodin alleviates severe acute pancreatitis-associated acute lung injury by decreasing pre-B-cell colony-enhancing factor expression and promoting polymorphonuclear neutrophil apoptosis.
Emodin alleviates severe acute pancreatitis-associated acute lung injury by decreasing pre-B-cell colony-enhancing factor expression and promoting polymorphonuclear neutrophil apoptosis.
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大黄素通过降低前B细胞集落增强因子表达并促进多形核中性粒细胞凋亡减轻重症急性胰腺炎相关的急性肺损伤
DOI：
10.3892/mmr.2017.7259
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发表时间：
2017-10
影响因子：
3.4
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Cui H;Li S;Xu C;Zhang J;Sun Z;Chen H
本研究旨在探讨大黄素对重症急性胰腺炎（SAP）相关急性肺损伤（ALI）的保护作用及其可能机制。通过逆行输注5%牛磺胆酸钠（1 ml/kg）在Sprague-Dawley大鼠中诱导SAP，之后将大鼠分成不同组，并给予大黄素、FK 866 [前B细胞集落增强因子（PBEF）的竞争性抑制剂]或地塞米松（DEX）。DEX用作阳性对照。随后，PBEF表达检测从大鼠外周血中分离的多形核中性粒细胞（PMNs）通过逆转录-定量聚合酶链反应和蛋白质印迹。此外，分别通过苏木精-伊红染色、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法、Annexin V/碘化丙啶（PI）法和蛋白质印迹法检测组织学改变、肺/胰腺组织细胞凋亡、外周血中性粒细胞凋亡和凋亡相关蛋白表达的变化。血清淀粉酶活性和湿/干（W/D）重量比也进行了测量。还进行了体外研究，其中从正常Sprague-Dawley大鼠获得PMN，并在脂多糖（LPS）存在下与大黄素、FK 866或DEX孵育。采用Annexin V/PI法和Western blotting法分别检测体外培养的PMNs凋亡及凋亡相关蛋白的表达水平。结果表明，大黄素、FK 866和DEX可显著下调外周血PMN PBEF的表达。此外，大黄素、FK 866和DEX通过调节凋亡相关蛋白Fas、Fas配体、B细胞淋巴瘤（Bcl）-2相关X蛋白、切割型caspase-3和Bcl-extra-large的表达，降低血清淀粉酶活性，降低肺和胰腺W/D比值，减轻肺和胰腺损伤，促进PMN凋亡。此外，体外研究表明，大黄素，FK 866和DEX可通过调节凋亡相关蛋白的表达，显著逆转LPS诱导的PMN凋亡减少。结论：大黄素可能通过降低PBEF表达，促进PMN凋亡，通过线粒体和死亡受体途径保护SAP相关的ALI。
The present study aimed to evaluate the protective effects of emodin on severe acute pancreatitis (SAP)-associated acute lung injury (ALI), and investigated the possible mechanism involved. SAP was induced in Sprague-Dawley rats by retrograde infusion of 5% sodium taurocholate (1 ml/kg), after which, rats were divided into various groups and were administered emodin, FK866 [a competitive inhibitor of pre-B-cell colony-enhancing factor (PBEF)] or dexamethasone (DEX). DEX was used as a positive control. Subsequently, PBEF expression was detected in polymorphonuclear neutrophils (PMNs) isolated from rat peripheral blood by reverse transcription-quantitative polymerase chain reaction and western blotting. In addition, histological alterations, apoptosis in lung/pancreatic tissues, apoptosis of peripheral blood PMNs and alterations in the expression of apoptosis-associated proteins were examined by hematoxylin and eosin staining, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay, Annexin V/propidium iodide (PI) assay and western blotting, respectively. Serum amylase activity and wet/dry (W/D) weight ratios were also measured. An in vitro study was also conducted, in which PMNs were obtained from normal Sprague-Dawley rats and were incubated with emodin, FK866 or DEX in the presence of lipopolysaccharide (LPS). Apoptosis of PMNs and the expression levels of apoptosis-associated proteins were examined in cultured PMNs in vitro by Annexin V/PI assay and western blotting, respectively. The results demonstrated that emodin, FK866 and DEX significantly downregulated PBEF expression in peripheral blood PMNs. In addition, emodin, FK866 and DEX reduced serum amylase activity, decreased lung and pancreas W/D weight ratios, alleviated lung and pancreatic injuries, and promoted PMN apoptosis by regulating the expression of apoptosis-associated proteins: Fas, Fas ligand, B-cell lymphoma (Bcl)-2-associated X protein, cleaved caspase-3 and Bcl-extra-large. In addition, the in vitro study demonstrated that emodin, FK866 and DEX significantly reversed the LPS-induced decrease of apoptosis in PMNs by regulating the expression of apoptosis-associated proteins. In conclusion, the present study demonstrated that emodin may protect against SAP-associated ALI by decreasing PBEF expression, and promoting PMN apoptosis via the mitochondrial and death receptor apoptotic pathways.
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影响因子：
3.7
作者：
Pang X;Liu J;Li Y;Zhao J;Zhang X
通讯作者：
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作者：
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作者：
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