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  • 學位論文

探討薑黃素對視網膜色素上皮細胞於高糖環境下之保護作用

To investigate the protection effect of Curcumin for retinal pigment epithelium cell under high glucose environment in vitro and in vivo

指導教授 : 蔡女滿

摘要


色素上皮細胞位於神經視網膜與脈絡膜之間,為單層的色素細胞所組成。當色素上皮細胞受損,則會使視網膜病變,甚至造成失明。全球因糖尿病引起視網膜病變者約有9300萬人,其中於病發後十年,第一型糖尿病患者皆會罹患糖尿病視網膜病變,而第二型糖尿病患者則大約60% 得病。糖尿病視網病變是由糖尿病導致內皮細胞功能受損而引起的微血管併發症,特徵為基底膜增厚、內皮細胞減少、血液視網膜障壁(BRB)崩解以及血管新生。薑黃素(Curcumin)在傳統中醫上被用於抗菌、抗發炎及改善潰瘍之功效,近期的研究發現薑黃素具有緩解腹痛及脹氣、抑制發炎及過敏、抑制腫瘤血管新生及轉移,誘發腫瘤細胞凋亡等功能。因此本實驗目的為:探討薑黃素對視網膜色素上皮細胞於高糖環境中之保護作用。實驗結果顯示,在高糖的環境下,會抑制色素上皮細胞(ARPE-19)的生長,當加入Curcumin維持細胞增生及細胞Tight junction及RPE65相關蛋白表達,達到保護色素上皮細胞之作用。於動物實驗中,低劑量之Curcumin能夠有效控制STZ所誘發之高血糖,降低其血糖濃度並穩定老鼠體重。透過病理分析,Curcumin能有降低高血糖所誘發的視網膜病變、保護色素上皮細胞,維持Tight junction及色素上皮細胞代謝功能。因此本實驗證實,Curcumin能夠有效保護色素上皮細胞於高糖的環境中生長,並降低高糖所導致的細胞病變及視網膜傷害,在未來糖尿病誘發的視網膜傷害中,提供多一項治療及預防的選擇。

並列摘要


The pigment epithelium cells constitute a single layer between retina and choroid. When the pigment epithelium cells are impaired, the retina will be damaged, posing a risk of blindness to patients. In the world, there are about 93 million people with retina damages induced diabetic hyperglycemia. After 10 years of suffering from diabetes mellitus (DM), diabetic retinopathy occurrs in all the patients with type I DM and in 60% patients with type II DM. Diabetic retinopathy is characterized by pigment epithelium damages, thickening of basal membrane, loss of pigment epithelium cells, breakdown of blood–retinal barrier and angiogenesis. Curcumin is tranditionally used due to its anti-bacteria, anti-inflammation and anti-ulcer effects. Recent studies futher showed that curcumin can nutigate stomachache and flatulence, inhibit inflammation and hypersensitivity, abrogate tumor angiogenesis and metastasis, and induce tumor cell apoptosis. Therefore, the purpose of this study is to investigate the protective effects of curcumin for retinal pigment epithelium cells under high glucose conditions in vitro and in vivo. The in vitro results showed that curcumin could protect pigment epithelium cells (ARPE-19) from high glucose-induced cell damage, and trigger cell proliferation and maintain tight junction related proteins and RPE65 expression. Results of in vivo study showed that low dose of curcumin (2 mg/kg) can regulate the blood glucose and stabilize the body weight of mice. In pathological analysis, curcumin could protect pigment epithelium cells and rescue tight junction and RPE65 expression in pigment epithelium cells. In conclusion, this study demonstrated that curcumin could protect pigment epithelium cells in high glucose environment in vitro and in vivo, and ameliorate the status of diabetic retinopathy and cell damages. In the future, curcumin may be potentially used for protection against diabetic retinopathy.

參考文獻


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