林中天臺灣大學:獸醫學研究所黃珮筠Huang, Pei-YunPei-YunHuang2010-05-042018-07-092010-05-042018-07-092008U0001-2207200813193100http://ntur.lib.ntu.edu.tw//handle/246246/178902美諾四環黴素(minocycline)是一種半合成、四環素(tetracycline)的第二代衍生物，應用於治療格蘭氏陰性菌或陽性菌的感染，近年來在許多研究腦部缺血或退化性疾病的實驗模式中，被發現具有神經保護的效果。篇研究目標在探討腹腔注射藥物minocycline是否對於視網膜缺血性病變有神經保護效果。本實驗採高眼內壓誘發視網膜缺血模式，大鼠眼前房以30號針頭穿刺，並連接上含生理食鹽水的點滴袋，將眼內壓提高到130mmHg，造成眼底視網膜完全缺血的狀態持續45分鐘。治療組分為兩個劑量，分別為每日45 mg/kg及90 mg/kg的minocycline腹腔注射。傷害評估利用缺血後第三天及第七天的視網膜電波圖，來檢查視網膜功能的改變，以及缺血後七天在組織病理形態及視網膜的厚度改變。其結果並和給予生理食鹽水和methylprednisolone的組別作比較分析。網膜電波圖的結果顯示，在給予缺血再灌流的傷害後，缺血眼的b波有顯著下降的趨勢(平均b波波幅損失74±2%)，而相對的a波影響較少。給予兩種劑量45 mg/kg及90 mg/kg的minocycline都有改善視網膜功能受損的情形，其視網膜電波圖的結果，分別為損失37±6%及43±2%的b波。組織病理結果顯示內層視網膜傷害均比外層強，而內叢狀層與外核層的比值(IPL/ONL ratio) 與正常的百分比分析（% of正常），缺血無治療組(IR-control)只剩下44.1%，45 mg/kg及90 mg/kg的minocycline治療組(Mino-45、Mino-90)顯示存留程度為93.4%和94.1%，而methylprednisolone治療組(MP)剩存的百分比可高達96.7%，幾乎沒有下降。根據結果指出，minocycline與methylprednisolone對於大鼠視網膜缺血再灌流模式，在組織病理的型態劑量上展現出良好的視網膜視網膜保護效果，而在視網膜功能方面可提供中等程度的神經保護效果。Minocycline, a microglial inhibitor, has recently been shown to be neuroprotective in various models of cerebral ischemia and degenerative diseases. The purpose of this study was to investigate the neuroprotective effect of intraperitoneal minocycline against the retinal ischemia-reperfusion (IR) injury in the rat. The retinal IR injury model was induced in Sprague-Dawley rats by infusing normal saline (0.9%) into anterior chamber of eye to creat a higher intraocular pressure (IOP) than blood pressure for 45 min. Minocycline was given intraperitoneally at dosages of 45 mg/kg per day and 90 mg/kg per day in rats of IR injury model. The effects were evaluated by electroretinogram (ERG) 3 days and 7 days after ischemia respectively, and compared with the groups treated with saline and methyprenisolone (30mg/kg, IV). Present results have indicated that ischemia-reperfusion (IR) injury caused retinal damage characterized by a decline in electroretinogram b-wave (loss of 74±2% b-wave, n=5) whereas the a-wave was relatively unaffected. Administration of minocycline in both doses ameliorated the damage of retinal function. The b-wave of ERG dropped down 37±6% in the 90 mg/kg/day group ( n=6) and 43±2% in the 45mg/kg/day group (n=6). In the morphometrical histology, the retinal inner plexiform layer/outer nuclear layer (IPL/ONL) ratio was reduced following IR damage compared with that in the normal control. The IPL/ONL ratio was reduced to 44.1% in the IR-control group, 93.4% and 94.1% in the Mino-45 and Mino-90 group. While the IPL/ONL ratio was preserved to 96.7% in the MP group. According to the results, minocycline and methylprednisolone showed significantly good neuroprotective effects demonstrated in histology, but moderate neuroprotective effects in retinal function of the rats under retinal ischemia-reperfusion injury.中文摘要............................................................1.文摘要............................................................2.一章 緒言........................................................4.一節 視網膜缺血性病變..........................................4.二節 視網膜神經保護概念與治療策略..............................4.、 視網膜缺血再灌流導致的傷害機轉............................4.、 神經保護策略及途徑........................................8.三節 視網膜缺血再灌流性病變之動物模式.........................10.、 簡介.....................................................10.、 視網膜缺血性病變評估.....................................11.四節 Minocycline的簡介與應用..................................14.五節 Methylprednisolone的治療策略..............................18.六節 研究目的.................................................19.二章 實驗材料與方法.............................................20.一節 實驗動物.................................................20.二節 實驗材料與分組...........................................20.三節 大鼠視網膜缺血再灌流模式.................................21.四節 藥物的劑量與投予.........................................21.五節 視網膜電波圖的紀錄與分析.................................22.六節 組織病理學切片評估.......................................23.七節 統計與分析方法...........................................24.三章 實驗結果...................................................25.一節 視網膜電波圖電生理分析結果...............................25.、 建立高眼內壓導致視網膜缺血再灌流模式.....................25.、 視網膜電波圖b-wave ratio下降幅度分析比較..................31.、 視網膜電波圖a波和b波綜合比較...........................39.二節 組織病理型態分析報告.....................................41.、 各層視網膜厚度病變比較...................................41.、 內叢狀層與外核層的比值分析...............................47.四章 討論.......................................................49.一節 視網膜缺血性病變的模式...................................49.二節 神經保護藥物的選擇.......................................50.三節 視網膜電波圖討論.........................................51.、 視網膜功能評估的選擇.....................................51.、 統計視網膜保護效力結果與文獻之討論.......................52.、 不同光源強度的使用與討論.................................56.四節 組織病理型態的討論.......................................59.、 缺血再灌流對病理型態上之影響.............................59.、 病理結果的統計與文獻之討論...............................60.五節 評估藥物保護效果.........................................62.五章 結論.......................................................64.六章 參考文獻...................................................65.application/pdf789970 bytesapplication/pdfen-US視網膜缺血神經保護視網膜電波圖美諾四環黴素再灌流性傷害retinal ischemia-reperfusion injuryischemia-reperfusion injuryminocyclineelectroretinogramneuroprotective effectthesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/178902/1/ntu-97-R94629032-1.pdf