Núñez M J, Balboa J, Riveiro P, Liñares D, Mañá P, Rey-Méndez M, Rodríguez-Cobos A, Suárez-Quintanilla J A, García-Vallejo L A, Freire-Garabal M
Neuroimmunology Laboratory, Department of Pharmacology, School of Medicine, University of Santiago de Compostela, 15705-Santiago de Compostela, Spain.
Clin Diagn Lab Immunol. 2002 Jul;9(4):852-7. doi: 10.1128/cdli.9.4.852-857.2002.
Psychological stress has been found to suppress cell-mediated immune responses that are important in limiting the proliferation of Candida albicans. Since anxiolytic drugs can restore cellular immunity in rodents exposed to stress conditions, we designed experiments conducted to evaluate the effects of alprazolam (1 mg/kg of body weight/day), a central benzodiazepine anxiolytic agonist, on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Application of stress and treatment with drugs (placebo or alprazolam) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments (day 15 postinoculation). Establishment of C. albicans infection was evaluated by swabbing the inoculated oral cavity with a sterile cotton applicator on days 2 and 15 after inoculation, followed by plating on YEPD (yeast extract-peptone-dextrose) agar. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results show that stress exacerbates C. albicans infection of the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by fungal hyphae were found in stressed rats compared to those found in the unstressed rats. Treatment with alprazolam significantly reversed these adverse effects of stress, showing that, besides the psychopharmacological properties of this anxiolytic drug against stress, it has consequences for Candida infection.
研究发现，心理压力会抑制细胞介导的免疫反应，而这种免疫反应对于限制白色念珠菌的增殖至关重要。由于抗焦虑药物能够恢复处于应激状态的啮齿动物的细胞免疫，我们设计了实验，以评估中枢苯二氮䓬类抗焦虑激动剂阿普唑仑（1毫克/千克体重/天）对暴露于慢性听觉应激源的斯普拉格-道利大鼠口腔念珠菌病发展的影响。为了促进白色念珠菌感染的建立和持续存在，对动物进行了手术性唾液分泌减少处理。在白色念珠菌接种前7天开始施加应激并给予药物治疗（安慰剂或阿普唑仑），持续至实验结束（接种后第15天）。在接种后第2天和第15天，用无菌棉签擦拭接种的口腔，然后接种于YEPD（酵母提取物-蛋白胨-葡萄糖）琼脂平板上，以此评估白色念珠菌感染的建立情况。通过对每个显微镜视野下舌背乳头的数量和类型（正常或异常）进行量化来确定组织损伤。设计了一个半定量量表来评估真菌菌丝对上皮的定植程度。我们的结果表明，应激会加剧大鼠舌头的白色念珠菌感染。与未应激的大鼠相比，应激大鼠的念珠菌计数、舌表面出现临床病变的百分比、异常乳头的百分比以及真菌菌丝对上皮的定植均显著增加。阿普唑仑治疗显著逆转了应激的这些不利影响，表明除了这种抗焦虑药物对抗应激的心理药理学特性外，它对念珠菌感染也有影响。
