侵袭性白假丝酵母菌感染小鼠模型中HMGB1的表达及意义

The expression and significance of HMGB1 in the mice model of invasive Candida albicans infection

目的研究高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)在侵袭性白假丝酵母菌感染小鼠模型中的表达及意义。方法 Balb/c小鼠腹腔注射环磷酰胺100 mg/(kg·d),连续3 d,检测小鼠血液中白细胞数量的变化。然后,通过尾静脉注射不同浓度的白假丝酵母菌悬液,选取合适的感染浓度并鉴定该浓度造模成功。将20只免疫抑制小鼠尾静脉注射白假丝酵母菌悬液,分别于感染后1、3、5和7 d处死小鼠,检测小鼠肝、肾功、C-反应蛋白等指标来明确小鼠病情严重程度,同时用Western blot检测小鼠肝、肺、肾组织中HMGB1的表达水平。结果本实验选取的侵袭性白假丝酵母菌感染的浓度为2×105/ml,组织培养和组织病理学方法均确定该浓度造模成功。生化结果显示,实验小鼠肝、肾功明显受损(总蛋白、球蛋白、谷草转氨酶、尿素、肌酐明显升高,胆碱酯酶明显降低)及C-反应蛋白明显升高。Western blot结果显示,实验组小鼠肝、肺、肾组织HMGB1的表达量均增加。肝组织HMGB1的表达量在第1天开始增加,第5天最明显(P<0.01);肺和肾组织第5天开始明显增加(P<0.01)。结论 HMGB1很可能在侵袭性白假丝酵母菌感染中起着重要作用。

This study designed to evaluate the expression and significance of HMGB1 in the mouse model of invasive Candida albicans infection. Healthy Balb/c mice were treated with cyclophosphamide at a dosage of100 mg/（kg·d） for 3 days via abdominal cavity to observe the changes of white blood cells of the mice. After that,Balb/c mice were infected via tail vein with the different solution of Candida albicans to select appropriate solution of infection. After 20 immunosuppressed mice were infected by Candida albicans, the liver, renal function and Creactive protein（CRP） were measured on days 1, 3, 5, and 7 after infection, and the expression levels of HMGB1 in liver, lung, kidney tissues were detected by Western blotting. The concentration of 2 ×105/ml was selected for invasive Candida albicans infection, and the model was constructed successfully confirmed by tissue culture and histopathological methods. Biochemical results revealed that liver and renal function was significantly impaired（TP,GLB, AST, BUN, CRE increased significantly, CHE decreased significantly） and CRP increased significantly in the experimental group; the result of Western blotting showed the expression of HMGB1 in liver, lung, kidney tissue increased in the experimental group. The expression of HMGB1 in liver tissue began to increase on the first day,and reached the peek at the fifth day（P 0.01）; while HMGB1 expression in lung and kidney tissue began to increase apparently in the fifth day（P 0.01）. From all the results, we get a conclusion that HMGB1 may play a key role in invasive Candida albicans infection.