Kim Jong Won, Jeong Hyuneui, Yang Myeon-Sik, Lim Chae Woong, Kim Bumseok
Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea.
Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea.
Int Immunopharmacol. 2017 Jul;48:126-134. doi: 10.1016/j.intimp.2017.05.005. Epub 2017 May 11.
Cornea is an avascular transparent tissue. Ocular trauma caused by a corneal alkali burn induces corneal neovascularization (CNV), inflammation, and fibrosis, leading to vision loss. The purpose of this study was to examine the effects of Zerumbone (ZER) on corneal wound healing caused by alkali burns in mice. CNV was induced by alkali-burn injury in BALB/C female mice. Topical ZER (three times per day, 3μl each time, at concentrations of 5, 15, and 30μM) was applied to treat alkali-burned mouse corneas for 14 consecutive days. Histopathologically, ZER treatment suppressed alkali burn-induced CNV and decreased corneal epithelial defects induced by alkali burns. Corneal tissue treated with ZER showed reduced mRNA levels of pro-angiogenic genes, including vascular endothelial growth factor, matrix metalloproteinase-2 and 9, and pro-fibrotic factors such as alpha smooth muscle actin and transforming growth factor-1 and 2. Immunohistochemical analysis demonstrated that the infiltration of F4/80 and/or CCR2 positive cells was significantly decreased in ZER-treated corneas. ZER markedly inhibited the mRNA and protein levels of monocyte chemoattractant protein-1 (MCP-1) in human corneal fibroblasts and murine peritoneal macrophages. Immunoblot analysis revealed that ZER decreased the activation of signal transducer and activator of transcription 3 (STAT3), with consequent reduction of MCP-1 production by these cells. In conclusion, topical administration of ZER accelerated corneal wound healing by inhibition of STAT3 and MCP-1 production.
角膜是一种无血管的透明组织。角膜碱烧伤引起的眼外伤会诱发角膜新生血管形成（CNV）、炎症和纤维化，导致视力丧失。本研究的目的是检测莪术酮（ZER）对小鼠碱烧伤引起的角膜伤口愈合的影响。通过碱烧伤损伤BALB/C雌性小鼠诱导CNV。局部应用ZER（每天3次，每次3μl，浓度分别为5、15和30μM）连续14天治疗碱烧伤的小鼠角膜。组织病理学上，ZER治疗可抑制碱烧伤诱导的CNV，并减少碱烧伤引起的角膜上皮缺损。用ZER处理的角膜组织显示促血管生成基因的mRNA水平降低，包括血管内皮生长因子、基质金属蛋白酶-2和9，以及促纤维化因子如α平滑肌肌动蛋白和转化生长因子-1和2。免疫组织化学分析表明，在ZER处理的角膜中，F4/80和/或CCR2阳性细胞的浸润显著减少。ZER显著抑制人角膜成纤维细胞和小鼠腹腔巨噬细胞中单核细胞趋化蛋白-1（MCP-1）的mRNA和蛋白水平。免疫印迹分析显示，ZER降低了信号转导子和转录激活子3（STAT3）的激活，从而减少了这些细胞产生的MCP-1。总之，局部应用ZER通过抑制STAT3和MCP-1的产生加速了角膜伤口愈合。
