李彗禎謝逸憲LEE, HUEI-JANEHSIEH, YI-HSIEN沈亭妤SHEN, TING-YUTING-YUSHEN醫學研究所碩士班2026-10-292030-08-2120252025-06-24https://handle.ncl.edu.tw/11296/nxyc49https://scholars.csmu.edu.tw/handle/123456789/36747視網膜色素上皮細胞 (retinal pigment epithelial cells, RPE cells)主要的功能是提供養分並清除代謝物以維持視網膜與脈絡膜的正常功能。發炎反應會導致視網膜色素上皮細胞的結構損傷、促進血管新生而形成視網膜病變。過去文獻指出，綠原酸 (Chlorogenic Acid, CGA)具有良好的抗發炎、抗氧化功效，可改善糖尿病周邊神經病變。本研究目的為探討高糖高脂誘導RPE細胞損傷，CGA是否具改善效用及潛在機轉。在細胞實驗中，我們測試人類視網膜色素上皮細胞ARPE-19，以100 mM的Glucose以及200 uM的棕櫚酸 (Palmitate acid, PA)模擬高糖高脂，同時處理CGA (70 uM)、其類似化合物nCGA (70 uM)、以及其在體內所產生的代謝物CA (5、25 uM)。在動物實驗的部分，我們選用5週齡的ApoE-/- mice連續5天施打鏈脲佐菌素 (Streptozotocin, STZ)(55 mg/kg)，2週後餵食高脂飲食 (High fat diet, HFD)及CGA (100 mg/kg/day)，持續8週。細胞實驗結果顯示，CGA以及nCGA可以有效的減少PI3K、AKT、mTOR磷酸化，並使PKC的磷酸化下降；SOD、E-cadherin表現量增加、 CHOP表現量下降。在動物實驗中，與高脂飲食組比較，CGA顯著降低血糖、HbA1C、TG、LDL及增加HDL，並減少視網膜CHOP蛋白量，增加超氧化物歧化酶 (Superoxide dismutase, SOD)與E-cadherin蛋白量，與細胞實驗結果一致，顯示出綠原酸能有效減少細胞發炎反應、增加細胞存活率，並穩定細胞黏附蛋白。在高血脂血糖小鼠中，則能降低血清血糖血脂，並在視網膜減少內質網壓力蛋白CHOP。本研究結果顯示綠原酸具延緩人類視網膜色素上皮細胞損傷的作用。The retinal pigment epithelium (RPE) plays a critical role in maintaining retinal and choroidal homeostasis by supplying nutrients and regulating metabolites. Inflammatory responses can disrupt RPE integrity, promote neovascularization, and ultimately lead to retinal pathologies. Chlorogenic acid (CGA), a naturally occurring polyphenol, has been reported to exhibit potent anti-inflammatory and antioxidant properties and has demonstrated efficacy in alleviating diabetic peripheral neuropathy. The present study aimed to evaluate whether CGA can ameliorate retinal pigment epithelial cell damage induced by high-glucose and high-fat conditions and to elucidate its potential underlying mechanisms. In vitro, human retinal pigment epithelial cells (ARPE-19) were exposed to 100 mM glucose and 200 uM palmitic acid to simulate a hyperglycemic and hyperlipidemic environment. Cells were concurrently treated with CGA (70 uM) its structural analog, neochlorogenic acid (nCGA, 70 uM) , and its in vivo metabolite, caffeic acid (CA, 5, 25 uM). Treatment with CGA or nCGA significantly reduced the phosphorylation levels of PI3K, AKT, mTOR, and PKC. Furthermore, the expression of superoxide dismutase (SOD) and E-cadherin was upregulated, while the expression of the endoplasmic reticulum stress marker CHOP was downregulated. In vivo, 5-week-old ApoE-/- mice were administered streptozotocin (STZ;55mg/kg) intraperitoneally for five consecutive days. Two weeks post-induction, mice were fed a high-fat diet (HFD) supplemented with CGA (100 mg/kg/day) for six weeks. Compared with HFD group, CGA treatment significantly decreased fasting blood glucose, HbA1c, triglycerides (TG), and low-density lipoprotein (LDL) levels, while increasing high-density lipoprotein (HDL) levels. CGA also markedly reduced CHOP protein levels and increased superoxide dismutase (SOD) and E-cadherin expression in retinal tissues, consistent with the in vitro findings. Collectively, these results suggest that CGA exerts a protective effect against high glucose and high fat-induced RPE damage by attenuating inflammatory signaling, enhancing antioxidative defenses, and maintaining cell adhesion. These findings support the potential of CGA as a therapeutic agent for retinal degenerative diseases associated with metabolic stress.人類視網膜色素上皮細胞綠原酸高糖高脂視網膜病變Human retinal pigment epithelial cellsChlorogenic acidHigh glucose and high fatRetinopathythesis