Resveratrol Ameliorates the Severity of Fibrogenesis in Mice with Experimental Chronic Pancreatitis
Resveratrol Ameliorates the Severity of Fibrogenesis in Mice with Experimental Chronic Pancreatitis
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白藜芦醇可改善实验性慢性胰腺炎小鼠纤维形成的严重程度。
DOI：
10.1002/mnfr.201700561
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发表时间：
2018-08-01
影响因子：
5.2
通讯作者：
Tsang, Siu Wai
中科院分区：
文献类型：
--
作者：
Xia, Yixuan;Xiao, Hai-Tao;Tsang, Siu Wai
适用范围：白藜芦醇通常被认为对健康和长寿有益，因为这种膳食芪类化合物已被仔细检查其对“救援基因”sirtuin-1的激活特性，该基因可促进细胞在压力下的存活。除了其抗衰老的特性，我们以前的体外研究表明，白藜芦醇显着抑制胰腺星状细胞（PSCs）细胞外基质（ECM）蛋白的产生，PSCs是对抗胰腺损伤的经典效应细胞。目的：我们的目的是外推白藜芦醇干预慢性胰腺炎小鼠纤维化的管理。方法和结果：对C57/BL 6小鼠重复注射雨蛙肽（50 μ gkg（-1）h（-1））6周以诱导慢性胰腺炎。我们证明，口服白藜芦醇（20 mg/kg/d）可有效减弱蓝蛋白诱导小鼠胰腺炎实质中PSC活化、ECM沉积、纤维形成和腺泡萎缩，损伤指数评分改善45.5%。增强细胞存活和保存腺泡的完整性，白藜芦醇considerably涉及一个永久的核积累Mist 1和Akt和p38 MAPK pathways.Conclusion的负调制：我们认为，白藜芦醇是一种潜在的营养药物，用于缓解慢性胰腺炎的胰腺纤维化，目前没有有效的治疗措施。
Scope: Resveratrol is generally considered beneficial to health-span and longevity since this dietary stilbenoid has been scrutinized for its activating property on the "rescue gene" sirtuin-1 that promotes cellular survival under stress. In addition to its antiaging property, our previous in vitro studies revealed that resveratrol notably inhibits the production of extracellular matrix (ECM) proteins in pancreatic stellate cells (PSCs), the classic effector cells against pancreatic injury.Objective: We aim to extrapolate resveratrol intervention to the management of fibrogenesis in mice with chronic pancreatitis.Methods and results: C57/BL6 mice are given repetitive injections of cerulein (50 mu gkg(-1) h(-1)) for 6 weeks for the induction of chronic pancreatitis. We demonstrate that the oral administration of resveratrol (20 mg kg(-1) d(-1)) effectively attenuated PSC activation, ECM deposition, fibrogenesis, and acinar atrophy in the pancreatitic parenchyma of cerulein-induced mice, as the damage index score was improved by 45.5%. The enhanced cell survival and preserved acinar integrity by resveratrol plausibly involves a perpetuated nuclear accumulation of Mist1 and a negative modulation of the Akt and p38 MAPK pathways.Conclusion: We suggest that resveratrol is potentially a nutraceutical for the mitigations of pancreatic fibrosis in chronic pancreatitis for which no effective therapeutic measure is currently available.