Departamento de Patologia e Clinica Animal, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Departamento de Zootecnia, Universidade do Estado de Santa Catarina, Chapecó, SC, Brazil.
Microb Pathog. 2017 Dec;113:124-128. doi: 10.1016/j.micpath.2017.10.012. Epub 2017 Oct 14.
The aim of this study was to evaluate the purine levels in serum and brains of mice experimentally infected by Cryptococcus neoformans. Twenty-four mice were divided into the following groups: a control group (n = 12; Group A) and an infection group with animals that were infected (n = 12; Group B) with a 0.3-mL intraperitoneal injection containing 1.7 × 10C. neoformans cells. Blood and brains were collected on days 20 (n = 6 per group) and 50 (n = 6 per group) post-infection (PI). Histopathology and lung and brain cultures were performed to confirm fungal infection and tissue injuries. The levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine (ADO), inosine (INO), hypoxanthine (HYPO), xanthine (XAN) and uric acid (UA) in brains and serum were measured by high-performance liquid chromatography (HPLC) analysis. At both time points, histopathology analysis revealed inflammatory infiltrates in the brains and lungs of infected mice; clinical signs, such as piloerection and clinical respiratory distress, were also observed. ATP levels were significantly increased on days 20 and 50 PI (P < 0.01) in brains and serum, while brain ADO levels were increased on day 20 PI; brain and serum ADO levels were decreased on day 50 PI. Levels of ADP and AMP did not differ between groups (P > 0.05). Serum levels of INO of infected mice increased only on day 50 PI (P < 0.05). HYPO levels were reduced in the brains of infected animals at both experimental time points and were decreased in serum at day 50 PI (P < 0.05). XAN levels increased in infected mice only in serum on day 50 PI (P < 0.05). The endogenous anti-oxidant uric acid was significantly increased in brain (days 20 and 50 PI) and decreased in serum. It is possible that C. neoformans infection in mice leads to a high ATP/ADO ratio that may improve the brain pro-inflammatory response during both periods, while high ATP levels in serum act as a systemic signal to improve the immune response. Moreover, the anti-oxidant uric acid may increase in the brain to protect inflamed tissue from oxidative stress.
本研究旨在评估实验性感染新型隐球菌的小鼠血清和脑组织中的嘌呤水平。将 24 只小鼠分为以下两组：对照组（n=12；A 组）和感染组（n=12；B 组），每组通过腹腔注射 0.3ml 含有 1.7×10C 的细胞进行感染。neoformans。在感染后第 20 天（每组 6 只）和第 50 天（每组 6 只）收集血液和脑组织。进行组织病理学检查以及肺和脑组织培养以确认真菌感染和组织损伤。通过高效液相色谱法（HPLC）分析测量脑组织和血清中三磷酸腺苷（ATP）、二磷酸腺苷（ADP）、一磷酸腺苷（AMP）、腺苷（ADO）、次黄嘌呤（INO）、次黄嘌呤（HYPO）、黄嘌呤（XAN）和尿酸（UA）的水平。在两个时间点，感染小鼠的脑组织和肺部均出现炎症浸润的组织病理学分析；还观察到直立和临床呼吸窘迫等临床症状。感染后第 20 天和第 50 天，脑组织和血清中 ATP 水平显著升高（P<0.01），而第 20 天，脑组织 ADO 水平升高；第 50 天，脑组织和血清 ADO 水平降低。ADP 和 AMP 水平在组间无差异（P>0.05）。感染小鼠的血清 INO 水平仅在第 50 天 PI 时升高（P<0.05）。在两个实验时间点，感染动物的脑组织中 HYPO 水平降低，第 50 天 PI 时血清中 HYPO 水平降低（P<0.05）。仅在第 50 天 PI 时，感染小鼠的血清 XAN 水平升高（P<0.05）。内源性抗氧化剂尿酸在大脑（第 20 天和第 50 天 PI）中显著增加，而在血清中减少。新型隐球菌感染可能导致小鼠高 ATP/ADO 比值，这可能在两个时期都改善大脑的促炎反应，而血清中的高 ATP 水平作为一种全身性信号，改善免疫反应。此外，大脑中的抗氧化剂尿酸可能增加以保护发炎组织免受氧化应激。
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