本文選題：脂氧素A4 + 口腔扁平苔蘚�。� 參考：《福建醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的 本課題通過研究脂氧素A4受體（ALX-R）及核因子-Bp65(NF-κBp65)在口腔扁平苔蘚（oral lichen planus，OLP）病灶和正常口腔黏膜（nomal oral mucosa，NOM）中的表達(dá)情況，以及不同濃度脂氧素A4類似物15-epi-LXA4對脂多糖（LPS）誘導(dǎo)角質(zhì)形成細(xì)胞(HaCaT細(xì)胞)所模擬的OLP炎癥模型的影響，探討LXA4對口腔扁平苔蘚的可能作用機(jī)制。 方法 第一部分：（1）獲取OLP及NOM組織，切片并HE染色，選取符合標(biāo)準(zhǔn)的標(biāo)本。（2）SP免疫組化法檢測ALX-R、NF-κBp65在OLP組織和NOM組織中的表達(dá)情況，并比較所測指標(biāo)在兩種組織中的表達(dá)差異及其相關(guān)關(guān)系。 第二部分：（1）采用10g/mL的LPS刺激HaCaT細(xì)胞，一定程度上模擬OLP局部免疫應(yīng)答環(huán)境，ELISA法觀察LPS作用時(shí)間長度分別為6、12、24h，所構(gòu)建的OLP細(xì)胞模型中免疫應(yīng)答產(chǎn)物IL-6的表達(dá)狀況；（2）運(yùn)用50、100、200nmol/L的15-epi-LXA4干預(yù)處理所建立的OLP細(xì)胞模型，分別于6、12、24小時(shí)提取細(xì)胞培養(yǎng)上清和總RNA，檢測分析15-epi-LXA4對OLP細(xì)胞模型IL-6分泌和NF-κBp65基因表達(dá)的影響。 結(jié)果 第一部分：（1）ALX-R蛋白在OLP和NOM中表達(dá)陽性率分別為43.3%、90%，兩者具有顯著性差異(P＜0.05)；（2）NF-Bp65蛋白在OLP組及NOM中表達(dá)強(qiáng)度分別為83.3%、20%，兩者具有顯著性差異(P0.01)，其中糜爛萎縮型高于網(wǎng)紋型組(P0.05)；（3）OLP和NOM中NF-κBp65表達(dá)水平與ALX-R表達(dá)水平呈負(fù)相關(guān)。 第二部分：（1）體外OLP炎癥模型中，免疫應(yīng)答產(chǎn)物IL-6表達(dá)量明顯增加，且表達(dá)量隨著時(shí)間的增加呈上升趨勢；（2）一定濃度的15-epi-LXA4能夠抑制NF-κBp65和IL-6的表達(dá)，200nmol/L的15-epi-LXA4對NF-κBp65和IL-6抑制效果最顯著(P＜0.05)。 結(jié)論 1、ALX-R在NOM中強(qiáng)表達(dá)，而在OLP中弱陽性表達(dá)，且其表達(dá)與NF-κBp65呈負(fù)相關(guān)，提示ALX-R表達(dá)缺陷可能與OLP的轉(zhuǎn)歸有一定關(guān)系； 2、不同臨床類型OLP的ALX-R表達(dá)無顯著性差異，而NF-κBp65的表達(dá)有差異，糜爛萎縮型高于網(wǎng)紋型組，可能與NF-κBp65介導(dǎo)大量炎癥因子的表達(dá)有關(guān)，這與臨床中糜爛型OLP炎癥更嚴(yán)重相符合； 3、LXA4類似物干預(yù)處理LPS誘導(dǎo)的OLP炎癥模型，，能抑制NF-κBp65信號通路及其下游炎癥介質(zhì)IL-6的表達(dá)，且呈濃度依賴性，這將為口腔扁平苔蘚的臨床治療提供可能的新契機(jī)，并為新藥的研發(fā)提供一定的理論依據(jù)，但尚需對LXA4在OLP中作用進(jìn)行更深入的研究。
[Abstract]:Purpose The purpose of this study was to investigate the expression of lipoxygen-A4 receptor ALX-Rand nuclear factor -Bp65NF- 魏 Bp65 in lichen planus oral (OLP) and normal oral mucosa- (NOM) of oral lichen planus (OLP), and to investigate the expression of ALX-R and Bp65NF- 魏 Bp65 in oral lichen planus (OLP) lesions and normal oral mucosa. The effects of different concentrations of lipoxygenA4 analogue 15-epi-LXA4 on OLP inflammatory model induced by lipopolysaccharide (LPS) in keratinocytes were studied. The possible mechanism of LXA4 on oral lichen planus was discussed. Method Part I: 1) OLP and NOM tissues were obtained, sections were stained with HE, and the standard specimens. The immunohistochemical method was used to detect the expression of ALX-RnNF- 魏 Bp65 in OLP and NOM tissues. The expression differences and their correlation between the two tissues were compared. Part two: 1) HaCaT cells were stimulated by LPS of 10g/mL. To a certain extent, the length of action of LPS observed by Elisa in simulated local immune response environment of OLP was 612 ~ 24 h. The expression of IL-6 in the OLP cell model was established. The OLP cell model was established by 15-epi-LXA4 intervention of 50100200nmol/L. The supernatants and total RNAs were extracted from the cultured cells at 6h 12h, respectively. The effects of 15-epi-LXA4 on the secretion of IL-6 and the expression of NF- 魏 Bp65 gene in OLP cell model were detected and analyzed. Result Part one: the positive rate of ALX-R protein expression in OLP and NOM was 43.3% and 90, respectively. There was significant difference between the two groups (P < 0.05). The expression intensity of NF-Bp65 protein in OLP group and NOM group was 83.33%. There was a significant difference between the two groups (P 0.01), and the erosive atrophy type was higher than that in reticular type group. There was a negative correlation between the expression of NF- 魏 Bp65 and the expression of ALX-R in P0. 05 OLP and NOM. Part two: 1) in OLP inflammatory model in vitro, the expression of IL-6 increased significantly, and the expression of 15-epi-LXA4 increased with time. (2) A certain concentration of 15-epi-LXA4 could inhibit the expression of NF- 魏 Bp65 and IL-6. 15-epi-LXA4 of 200nmol / L had the most significant inhibitory effect on NF- 魏 Bp65 and IL-6 (P < 0.05). Conclusion 1ALX-R was strongly expressed in NOM, but weakly positive in OLP, and its expression was negatively correlated with NF- 魏 Bp65, suggesting that ALX-R expression defect may be related to the outcome of OLP; (2) there was no significant difference in the expression of ALX-R in different clinical types of OLP, but the expression of NF- 魏 Bp65 was higher in erosive atrophic type than in reticular type, which may be related to the expression of a large number of inflammatory factors mediated by NF- 魏 Bp65, which was in line with the severity of OLP inflammation in clinical practice. 3LXA4 analogue can inhibit the expression of NF- 魏 Bp65 signaling pathway and its downstream inflammatory mediator IL-6 in a concentration-dependent manner, which may provide a new opportunity for clinical treatment of oral lichen planus. It also provides some theoretical basis for the research and development of new drugs, but the role of LXA4 in OLP needs to be further studied.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R781.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前5條

1 汪群;諸煥穎;孫紅英;;人口腔扁平苔蘚角質(zhì)形成細(xì)胞的體外培養(yǎng)及生物學(xué)鑒定[J];復(fù)旦學(xué)報(bào)(醫(yī)學(xué)版);2007年05期

2 周曉燕,袁萍,葉篤筠;免疫球蛋白樣轉(zhuǎn)錄物3和4在移植耐受中的作用[J];生命的化學(xué);2004年06期

3 楊靈瀾,葉萍,馬莉,秦蓉暉,程斌中;口腔扁平苔蘚移植嚴(yán)重聯(lián)合免疫缺陷小鼠的實(shí)驗(yàn)研究[J];實(shí)用口腔醫(yī)學(xué)雜志;2005年02期

4 張力;吳萍;萬敬員;周曉燕;熊維;袁萍;李詠生;葉篤筠;;脂氧素對Jurkat T細(xì)胞增殖和白細(xì)胞介素-2/白細(xì)胞介素-2受體表達(dá)的影響[J];中國病理生理雜志;2008年01期

5 李潔婷;柳志文;;口腔扁平苔蘚治療進(jìn)展[J];中國實(shí)用口腔科雜志;2010年03期

本文編號：1912995