论文部分内容阅读
目的探讨群体感应分子法尼醇(Farnesol)联合钙调神经磷酸酶抑制剂环孢菌素A(CSA)对白色念珠菌的生物膜形成、形态转换、生长及活性、耐药性、凋亡反应和氧化应激反应的作用及其相关机制。方法体外构建生物膜状态白色念珠菌,分别经CSA、Farnesol、Farnesol联合CSA处理后,用qRT-PCR法检测生物膜状态白色念珠菌中生物膜形成过程中的相关基因CDR1、CEK1、CPH1、EFG1、ERG11、GPR1、HAT1、MDR1、HWP1、ALS3、TUP1mRNA表达水平的变化。结果白色念珠菌均具有不同程度的产膜能力,且单用CSA、Farnesol抗真菌药物对白色念珠菌生物膜的抑制率很低,而联合使用时,受试菌生物膜生长状态受到明显抑制。从临床血流感染中分离获得1株强产生物被膜白色念珠菌,命名为CA NX05;经不同药物组处理后生物膜状态白色念珠菌中的生物膜菌丝形成相关基因CEK1、CPH1、EFG1、ERG11、GPR1、HAT1、HWP1、ALS3、TUP1与其耐药性相关基因CDR1、MDR1的mRNA表达量与空白处理组相比均显著降低(F_(CEK1)=15.725,F_(CPH1)=6.230,F_(EFG1)=87.817,F_(ERG11)=17.527,F_(GPR1)=21.793,F_(HAT1)=65.318,F_(HWP1)=550.531,F_(ALS3)=10.514,F_(TUP1)=16.580,F_(CDR1)=8.089,F_(MDR1)=7.228;F>P,P<0.05)。结论群体感应分子Farnesol联合CSA处理较CSA及Farnesol处理能更有效地抑制白色念珠菌生物膜的形成,从而使其对抗真菌药物的敏感性增加,为临床合理使用抗真菌药物提供了科学导向。
OBJECTIVE: To investigate the biofilm formation, morphological transformation, growth and activity, drug resistance and apoptosis of Candida albicans, a combination of Farnesol and calcineurin inhibitor cyclosporin A (CSA) And the role of oxidative stress and its related mechanisms. Methods The biofilm Candida albicans was constructed in vitro. After treated with CSA, Farnesol, Farnesol and CSA, the related genes of CDR1, CEK1, CPH1 and EFG1 in biofilm formation during Candida albicans biofilm were detected by qRT-PCR. , ERG11, GPR1, HAT1, MDR1, HWP1, ALS3, TUP1 mRNA expression levels. Results Candida albicans had different levels of membrane-forming ability. When CSA was used alone, the inhibitory rate of Farnesol antifungal drug against Candida albicans biofilm was very low. When used in combination, the biofilm growth of tested bacteria was significantly inhibited. A strain of Candida albicans, a strong biofilm, was isolated from clinical bloodstream infection and named as CA NX05. The biofilm-forming genes CEK1, CPH1, EFG1, The mRNA expression levels of ERG11, GPR1, HAT1, HWP1, ALS3, TUP1 and their drug resistance related genes CDR1 and MDR1 were significantly decreased compared with the blank group (F_ (CEK1) = 15.725, F_ (CPH1) = 6.230, F_ EFG1 = 87.817, F_ (ERG11) = 17.527, F_ (GPR1) = 21.793, F_ (HAT1) = 65.318, F_ (HWP1) = 550.531, F_ (ALS3) = 10.514, F_ (TUP1) = 16.580, F_ ) = 8.089, F MDR1 = 7.228; F> P, P <0.05). Conclusion Farnesol combined with CSA treatment can inhibit the formation of Candida albicans biofilm more effectively than CSA and Farnesol treatment, thus increasing its sensitivity to antifungal drugs and providing a scientific guideline for the rational use of antifungal agents in clinical practice.