麝香草酚抗真菌活性及麝香草酚对酿酒酵母表达谱影响的研究
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摘要
临床上感染性疾病主要由细菌、真菌或病毒三大类微生物引起,治疗真菌性感染性疾病是临床抗感染治疗的重要组成部分。近年来,真菌的发病率不断升高,人们对真菌的研究也开始逐渐重视。目前临床上使用有效治疗药物不是毒性太大就是易产生耐药性致使复发率和再感染率升高,并有一些不良反应,而使其临床应用受到限制,因此急需开发出高效、低毒的抗真菌新型药物。从中草药中寻找抗真菌新药已成为非常重要的研究方向,近百年来,人们已发现300余种中药具有抗真菌活性。麝香草酚(THY),来源于麝香草属的植物百里香及陈皮。THY广泛用于抗菌,防腐,消毒,也有显著的抗病原性真菌活性。联合用药可谓是治疗真菌感染的有效治疗方案。通过联合用药来提高抗真菌药物的治疗效果和减少药物的毒性。本研究考察了THY对临床分离耐药真菌的体外敏感性及THY与两性霉素B(AMB)和氟康唑(FLC)联合应用抗临床分离耐药真菌的体外药物敏感性,并运用基因芯片从分子水平研究了THY对模式真菌酿酒酵母的作用机制,通过表型试验验证了芯片结果。研究结果表明,THY具有较好的抗真菌活性,THY与FLC和AMB有明显的体外协同抗临床分离耐药真菌的活性。本研究为探索THY作用靶标和天然药物THY的深开发奠定基础,为临床治疗真菌感染提供了新型的有效治疗方案。
Clinical infectious diseases by bacteria, fungi or viruses cause three main types of micro-organisms, so the treatment of fungal infections is an important part of clinical anti-infective treatment. In recent years, with tumor and AIDS patients increasing, organ transplants, and duct intubation and endoscope technology to carry out widespread and a wide range of applications of efficient broad-spectrum antibiotics, immunosuppressants and glucocorticoids, more and more often fungal infections see. Clinically, many years amphotericin B, and azole drug are special effect and first-choice drugs of treatment of fungal infections. However, renal toxicity caused by amphotericin B, narrow-spectrum treatment of azole drugs and emergence of drug-resistant strains, making an in-depth study of fungus-resistant mechanisms, and to overcome and slow down the development of drug resistance, the development of new safe and effective antifungal agents are particularly prominent. China's rich traditional Chinese medicine resources in the search for effective antifungal agents has aroused widespread attention. Thymol (Thymol), from the plants of thyme and oregano and tangerine peel. Research shows that thymol widely used anti-bacterial, anti-corrosion and disinfection. It is worth noting that it has significant activity of disease-resistant pathogenic fungi.
Global gene expression profile can be analyzed quickly and systematically in the whole genome level of gene expression by use of DNA microarray. And through monitoring the concentration of mRNA can be done specifically for each gene analysis. Using microarrays on a biological analysis of all the genes in parallel model for the understanding of gene function can provide some clues (target identification). Yeast as a model eukaryotic, has many similarities with higher eukaryotic life in the adjustment mechanism and is a ideal model to study the mechanism of antifungal agents.
This study researched on in vitro drug sensitivity of thymol against clinical isolates of fungi alone and in combination with fluconazole and amphotericin B. Notablely, this study in the international arenas for the first time analyzed the expression profile of thymol effected on Saccharomyces cerevisiae and explain the molecular mechanism of thymol effected on Saccharomyces cerevisiae. Furthermore, the results of DNA microarray has been verified by using RT-PCR and chip-related phenotype tcDNA has been done. The results show that thymol fluconazole and significantly synergy when thymol was in combination with fluconazole and amphotericin B; The results of gene expression profile show that the 517 genes differentially expressed, 305 genes upregulated and 212 genes downregulated. On this basis, we used advanced cluster analysis software, T-profiler to analyze the data. At the same time, RT-PCR tcDNA showed the good results consistent with the results of the microarray. In addition, glucose-dependent efflux of rhodamine 6G from Saccharomyces cerevisiae showed that thymol can activate efflux pump of Saccharomyces cerevisiae.
Clinical infectious diseases by bacteria, fungi or viruses cause three main types of micro-organisms, so the treatment of fungal infections is an important part of clinical anti-infective treatment. In recent years, with tumor and AIDS patients increasing, organ transplants, and duct intubation and endoscope technology to carry out widespread and a wide range of applications of efficient broad-spectrum antibiotics, immunosuppressants and glucocorticoids, more and more often fungal infections see. Clinically, many years amphotericin B, and azole drug are special effect and first-choice drugs of treatment of fungal infections. However, renal toxicity caused by amphotericin B, narrow-spectrum treatment of azole drugs and emergence of drug-resistant strains, making an in-depth study of fungus-resistant mechanisms, and to overcome and slow down the development of drug resistance, the development of new safe and effective antifungal agents are particularly prominent. China's rich traditional Chinese medicine resources in the search for effective antifungal agents has aroused widespread attention. Thymol (Thymol), from the plants of thyme and oregano and tangerine peel. Research shows that thymol widely used anti-bacterial, anti-corrosion and disinfection. It is worth noting that it has significant activity of disease-resistant pathogenic fungi.
Global gene expression profile can be analyzed quickly and systematically in the whole genome level of gene expression by use of DNA microarray. And through monitoring the concentration of mRNA can be done specifically for each gene analysis. Using microarrays on a biological analysis of all the genes in parallel model for the understanding of gene function can provide some clues (target identification). Yeast as a model eukaryotic, has many similarities with higher eukaryotic life in the adjustment mechanism and is a ideal model to study the mechanism of antifungal agents.
This study researched on in vitro drug sensitivity of thymol against clinical isolates of fungi alone and in combination with fluconazole and amphotericin B. Notablely, this study in the international arenas for the first time analyzed the expression profile of thymol effected on Saccharomyces cerevisiae and explain the molecular mechanism of thymol effected on Saccharomyces cerevisiae. Furthermore, the results of DNA microarray has been verified by using RT-PCR and chip-related phenotype tcDNA has been done. The results show that thymol fluconazole and significantly synergy when thymol was in combination with fluconazole and amphotericin B; The results of gene expression profile show that the 517 genes differentially expressed, 305 genes upregulated and 212 genes downregulated. On this basis, we used advanced cluster analysis software, T-profiler to analyze the data. At the same time, RT-PCR tcDNA showed the good results consistent with the results of the microarray. In addition, glucose-dependent efflux of rhodamine 6G from Saccharomyces cerevisiae showed that thymol can activate efflux pump of Saccharomyces cerevisiae.
引文
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