臺灣博碩士論文加值系統

研究目的：雷射屈光手術是目前常見用於治療近視、遠視、散光的方法。而本研究在於探討術後在角膜傷口癒合的過程中：(Moxifloxacin, MOX)在分泌作用、遷移作用和增生作用之中可能扮演的角色為何。
研究方法：利用TGF-β1模擬角膜傷口的環境，培養人類角膜纖維母細胞(human corneal fibroblasts, HCF) 並運用墨點分析法和西方墨點法分析第12型介白素的表現量，和MOX之間可能的調控機制。利用HCF在MOX的培養之下，觀察其遷移速率有無受到改變。最後分析內生性的FBLN1在HCF可能的功能性、MOX培養HCF的生長曲線、以及可能影響增生作用的因素為何(JNK, p53, p21, Bcl-2, Bcl-xL and survivin)。
結果與討論：收集培養基後做墨點分析法實驗，結果在第2天時明顯的會被TGF-β1誘導出來，尤其是到了第3天更是大量的被誘導出來，約是第1天的3.7倍。而在MOX的作用之下，由TGF-β1所誘導的現象則會被抑制下來。HCF隨著MOX的濃度增加而減緩了遷移的速率。MOX抑制了內生性FBLN1的表現量，在第3天時從8倍降為3.5倍，HCF的生長速率也由3倍降為1.7倍。MOX可能透過抑制了內生性FBLN1的表現量，影響內生性FBLN1的功能性，使細胞的貼附力變差，來抑制了增生作用。MOX活化了JNK，增加p-JNK的表現量；增加了Bcl-2、Bcl-xL和survivin的表現量，可能增加了細胞抗凋亡的能力；縱使也增加了p53和p21的表現量，卻沒有明顯的細胞凋亡現象，只是讓HCF的生長速率變慢而已。
結論：MOX可能發揮了其抗生素的作用，抑制了HCF的分泌作用、遷移作用和增生作用。此結果對於術後角膜的傷口癒合可能帶來好處：大幅降低了術後感染的風險，也降低了角膜細胞老化的可能性，使得角膜傷口能夠慢慢痊癒。

Aim：Laser refractive surgery is commonly used to treat myopia, hyperopia, astigmatism. The present study is to explore the postoperative corneal wound healing process: the possible role of Moxifloxacin (MOX) in secretion, migration and proliferation.
Methods：TGF-β1 modulates wound environment, cultured human corneal fibroblasts (HCF) and uses dot blotting and Western blotting to analyze the expression of interleukin-12, and possible regulatory mechanisms for MOX. Observe the migration rate under culturing HCF in MOX treatment. Final analysis functional of endogenous FBLN1 in HCF, cultured HCF growth curve in MOX treatment, and the factors (JNK, p53, p21, Bcl-2, Bcl-xL and survivin) that may affect proliferation.
Results and discussion：The medium was collected after dot blotting analysis of experimental results of the second day will be apparent induction by TGF-β1, in particular to the day 3 be induced a large number, which is about the first day of 3.7 times. The TGF-β1-induced phenomena will be suppressed down by MOX. HCF with increasing concentrations of MOX and slowed the rate of migration. MOX inhibits the expression of endogenous FBLN1, in the day 3 reduced from 8 times to 3.5 times, HCF the growth rate is also reduced by 3 times to 1.7 times. MOX suppressed the expression of endogenous FBLN1, affect the functionality of endogenous FBLN1, the cell adhesion force variation, to inhibit the proliferative effect. MOX activation of JNK, increased the expression of p-JNK; increased Bcl-2, Bcl-xL and survivin expression levels, which may increase the anti-apoptotic ability; although also increased the expression of p53 and p21, but no obvious apoptosis phenomenon, but the HCF growth rate slowed.
Conclusion：MOX may play a role in its antibiotic, inhibits HCF secretion, the migration and proliferation. The results for corneal wound healing potential benefits: significantly reduces the risk of postoperative infection, but also reduces the possibility of corneal cell aging, making corneal wound to heal slowly.

第一章 緒論 1
1.1 研究背景 1
1.2 研究目的 1
1. 3研究假說 2
第二章 文獻回顧 3
2.1 眼角膜術後傷口癒合 3
2.1.1 眼睛雷射屈光手術 3
2.1.2 角膜傷口癒合機制 4
2.1.3 術後傷口照護 6
2.2 抗生素的種類 6
2.2.1 喹諾酮/氟喹諾酮 7
2.3 影響HCF增生作用的因素 7
2.3.1 Fibulin 7
2.3.2 其他常見關於細胞增生作用的途徑 9
2.3.2.1 JNK 9
2.3.2.2 p53 / p21 10
2.3.2.3 Bcl-2 / Bcl-xL 10
2.3.2.4 survivin 11
第三章 實驗材料與方法 12
3.1 實驗藥品 12
3.2 儀器設備 12
3.3 實驗流程 13
3.4 實驗方法 13
3.4.1第12型介白素定量分析 13
3.4.1.1初代培養人類角膜纖維母細胞 (HCF) 13
3.4.1.2墨點分析法 13
3.4.1.3西方墨點法 14
3.4.2細胞遷移實驗 16
3.4.3增生作用分析 17
3.4.3.1抑制內生性的FBLN1 (shFBLN1) 17
3.4.3.2 WST-1 assay 18
3.4.3.3西方墨點法分析FBLN1的含量 19
3.4.3.4分析不同劑量的MOX對於HCF增生作用的影響 19
3.4.3.5西方墨點法分析其他關於增生作用途徑的蛋白質 20
3.4.4統計軟體與分析 20
第四章 結果與討論 21
4.1第12型介白素定量分析 21
4.1.1第12型介白素墨點分析法結果 21
4.1.2第12型介白素西方墨點法結果 22
4.2細胞遷移結果 24
4.3增生作用分析 25
4.3.1 shFBLN1細胞型態 25
4.3.2 抑制shFBLN1的效率分析 26
4.3.3 shFBLN1的生長曲線圖 27
4.3.4 內生性FBLN1西方墨點法結果 27
4.3.5 經過MOX處理所得HCF的生長曲線圖 28
4.3.6 p-JNK西方墨點法結果 30
4.3.7 p53、p21西方墨點法結果 31
4.3.8 Bcl-2、Bcl-xL西方墨點法結果 32
4.3.9 survivin西方墨點法結果 33
第五章 結論與展望 35
第六章 參考資料 37

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