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ALA光動(dòng)力療法控制金黃地鼠皮脂腺斑痤瘡丙酸桿菌感染后炎癥的研究

發(fā)布時(shí)間:2019-05-16 06:51
【摘要】:背景:多國健康監(jiān)測系統(tǒng)統(tǒng)計(jì)數(shù)據(jù)顯示,人群中約有85%在12~24歲期間出現(xiàn)痤瘡,嚴(yán)重影響患者人群的身心健康。痤瘡丙酸桿菌(Propi-onibacterium acnes,Pacnes)在痤瘡形成中起重要作用,其代謝產(chǎn)物如脂肪酶、蛋白酶、透明質(zhì)酸酶和趨化因子均可引起炎癥反應(yīng)。皮膚脂質(zhì)除了為Pacnes大量增殖提供厭氧環(huán)境外,其中的一些成分也直接或間接參與了痤瘡炎癥的發(fā)生。光動(dòng)力療法(Photod3rnarnic 111er.dpy,PDT)是一種正在研究發(fā)展中的新型醫(yī)療技術(shù),光動(dòng)力療法的優(yōu)點(diǎn)主要是組織選擇性強(qiáng),對(duì)正常組織不會(huì)造成損害。5.氨基乙酰丙酸(5.a(chǎn)rnin01evulink:acid,,ALA)誘導(dǎo)產(chǎn)生的原卟啉Ix對(duì)皮脂腺有很強(qiáng)的選擇性。局部用ALA在人體毛囊和皮脂腺中轉(zhuǎn)變成有效的光敏劑(原卟啉Ix),在細(xì)菌中轉(zhuǎn)變成光敏劑(糞卟啉或尿卟啉),經(jīng)光激發(fā)引起光動(dòng)力反應(yīng),繼而抑制皮脂分泌,滅活皮膚角化細(xì)胞并殺滅毛囊中的致病菌。 目的:本研究旨在觀察5氨基乙酰丙酸光動(dòng)力療法(5.a(chǎn)rnin01eVIIIlinic acid:Photodynarnic T11er.dp)_,ALA-PDT)對(duì)Pacnes感染金黃地鼠皮脂腺斑炎癥的抑制作用,并進(jìn)一步探討ALA.PDT抗炎治療的作用機(jī)理,為皮膚科臨床應(yīng)用ALA PDT治療痤瘡炎癥提供實(shí)驗(yàn)依據(jù)。 方法:①取健康金黃地鼠16只,隨機(jī)分為4組:I組為空白對(duì)照組、II組為Pacnes組、III組為Pacnes+ALA.PDT組、Ⅳ組為Pacnes+紅光組。厭氧環(huán)境下培養(yǎng)痤瘡丙酸桿菌并接種于II、III、Ⅳ組金黃地鼠皮脂腺斑,誘導(dǎo)炎癥反應(yīng)產(chǎn)生,1周后進(jìn)行光動(dòng)力治療。②對(duì)III組金黃地鼠皮脂腺斑區(qū)域先外敷20%.ALA1h后進(jìn)行紅光照射,而Ⅳ組只用紅光照射。照光方案為每周1次,共4周。照射參數(shù)為:能量密度127 J/cm。波長633±3 nm,光斑大小1 O cm,設(shè)定時(shí)間為15min。3分別切取各實(shí)驗(yàn)組皮脂腺斑進(jìn)行組織學(xué)觀察及特殊染色。4酶聯(lián)免疫吸附測定血清睪酮與雌二醇水平。5westernblot檢測炎癥信號(hào)通路相關(guān)蛋白NF.KB和s_lXI3蛋白表達(dá)水平。 結(jié)果: 1.光動(dòng)力治療后皮脂腺斑炎癥反應(yīng)減少與P.lcnes組比較,ALA.PDT和單純紅光照射均能減輕痤瘡丙酸桿菌感染引起的以炎細(xì)胞浸潤為主的炎癥性改變。ALA.PDT組對(duì)皮脂腺斑組織的炎癥抑制效果顯著強(qiáng)于單純紅光組。 2.光動(dòng)力治療對(duì)血清睪酮,雌二醇水平的影響與空白對(duì)照組比較,ALA.PDT和單純紅光照射均未引起血清睪酮,雌二醇水平的顯著差異(PO 05)。 3.光動(dòng)力治療對(duì)NF—KB和sTAT3蛋白表達(dá)水平的影響與P.lcnes組比較,光動(dòng)力治療后NF.KB蛋白表達(dá)水平明顯降低,而s_lXI蛋白表達(dá)升高。ALA.PDT組對(duì)皮脂腺斑組織炎癥信號(hào)通路相關(guān)蛋白表達(dá)抑制效果顯著強(qiáng)于單純紅光組,差異均具有統(tǒng)計(jì)學(xué)意義(PO 05)。 結(jié)論:光動(dòng)力療法通過改變炎癥信號(hào)通路相關(guān)蛋白NF.KB和s_lXI的表達(dá),可對(duì)痤瘡丙酸桿菌引起的皮脂腺炎癥反應(yīng)有良好的抑制效果。光動(dòng)力治療不影響金黃地鼠血清睪酮和雌二醇的表達(dá)水平。
[Abstract]:Background: according to the statistics of multinational health monitoring system, about 85% of the population developed acne during the age of 12 years, which seriously affected the physical and mental health of the patients. Propionium acnes (Propi-onibacterium acnes,Pacnes) plays an important role in acne formation. Its metabolites such as lipase, protease, hyaluronidase and chemokines can cause inflammation. In addition to providing an anaerobic environment for the proliferation of Pacnes, some of its components are also directly or indirectly involved in the occurrence of acne inflammation. Photodynamic therapy (Photod3rnarnic 111er.dpy, PDT) is a new medical technology under development. Photodynamic therapy has the advantages of strong tissue selectivity and no damage to normal tissue. 5. 5. Aminolevulinic acid (5.arnin01evulink acid, PDT) is a new medical technology in the process of research and development. the main advantages of photodynamic therapy are that it has strong tissue selectivity and does not cause damage to normal tissue. 5. Aminolevulinic acid, ALA) induced protoporphyrin Ix has strong selectivity to sebaceous gland. Local use of ALA into an effective photosensitizer in human hair follicles and sebaceous gland (protoporphyrin Ix), is transformed into photosensitizer (fecal porphyrin or uroporin) in bacteria, which can induce photodynamic reaction and then inhibit sebum secretion. Inactivate keratinized cells of the skin and kill pathogenic bacteria in hair follicles. Objective: to observe the inhibitory effect of 5-aminolevulinic acid photodynamic therapy (5.arnin01eVIIIlinic acid:Photodynarnic T11er.dp) _ (ALA-PDT) on sebaceous gland plaque inflammation in golden hamsters infected with Pacnes. To further explore the mechanism of anti-inflammatory therapy of ALA.PDT, and to provide experimental basis for clinical application of ALA PDT in the treatment of acne inflammation. Methods: 1 Sixteen healthy golden hamsters were randomly divided into 4 groups: group I was blank control group, II group was Pacnes group, III group was Pacnes ALA.PDT group, group IV was Pacnes red light group. Propionium acnes was cultured in anaerobically environment and inoculated with II,III, IV golden hamster sebaceous gland spot to induce inflammatory reaction. One week later, photodynamic therapy was performed. 2 the area of sebaceous gland spot of golden hamster in III group was irradiated with red light after external application of 20%.ALA1h, while group IV was irradiated with red light only. The lighting scheme is once a week for 4 weeks. The irradiation parameters are as follows: energy density 127 J / cm. Wavelength 633 鹵3 nm, spot size 1 O cm, The time was set at 15min.3 for histologic observation and special staining of sebaceous gland plaques in each experimental group. 4 the levels of serum testosterone and estrogen were measured by enzyme-linked immunosorbent assay (Elisa). The inflammatory signaling pathway related proteins NF.KB and Estradiol were detected by Western Blot. The expression level of s_lXI3 protein. Results: 1. Compared with P.lcnes group, the inflammatory reaction of sebaceous plaques decreased after photodynamic therapy. Both ALA.PDT and simple red light irradiation could alleviate the inflammatory changes mainly caused by inflammatory cell infiltration caused by propionic acid bacillus acnes infection. The inhibitory effect of ALA.PDT group on sebaceous ganglia tissue was significantly stronger than that of simple red light group. 2. The effect of photodynamic therapy on serum testosterone and Estradiol levels was not significantly different from that of blank control group (PO 05). There was no significant difference in serum testosterone and estrogen levels between ALA.PDT and red light irradiation alone. 3. The effect of photodynamic therapy on the expression of NF-KB and sTAT3 protein was significantly lower than that of P.lcnes group after photodynamic therapy. However, the expression of s_lXI protein was increased. The inhibitory effect of ALA.PDT group on the expression of inflammatory signal pathway-related proteins in sebaceous ganglia tissue was significantly stronger than that in simple red light group (PO 05), and the effect of ALA.PDT group was significantly higher than that of simple red light group (ALA.PDT group). Conclusion: photodynamic therapy can inhibit the inflammatory reaction of sebaceous gland induced by propionic acid acne by changing the expression of NF.KB and s_lXI. Photodynamic therapy did not affect the expression of serum testosterone and estrogen in golden hamsters.
【學(xué)位授予單位】:南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2010
【分類號(hào)】:R758.733

【共引文獻(xiàn)】

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