白色假丝酵母菌感染致严重脓毒血症大鼠模型的建立

Establishment of rat model with severe sepsis due to Candia albicans infections

目的采用尾静脉注射法初步建立白色假丝酵母菌感染所致严重脓毒血症动物模型,为进一步研究人类该疾病的发生、发展规律及预防、治疗提供实验依据。方法清洁级雄性Wister大鼠48只,随机分为6组,每组8只,对照组给予尾静脉注射生理盐水1ml/kg,其余5组给予尾静脉注射白色假丝酵母菌液1ml/kg(浓度为4×108集落形成单位/L)造成严重脓毒血症;分别于6、12、24、36、48h各时间点采血检测血常规及生化指标,并观察大鼠肝、心、肺、肾等组织病理学形态改变。结果各处理组血常规白细胞及生化指标、谷草转氨酶、尿素、肌酐与对照组均有显著差异,其中白细胞于6h开始逐渐降低,于24h时达最低值,之后有所上升;谷草转氨酶6h开始升高,12h升高明显,在24h时达高峰,之后逐渐下降;尿素和肌酐在6、12h变化不明显,在24h及之后有大幅度上升,48h达高峰,病理形态学检查显示动物多个器官明显受损。结论大鼠尾静脉注射白色假丝酵母菌液可致大鼠体内广泛炎症反应,并伴有多器官损伤,其改变符合严重脓毒血症的标准和特征,该研究成功建立白色假丝酵母菌脓毒症动物模型,为真菌脓毒血症研究奠定基础。

OBJECTIVE To initially establish the animal model with severe sepsis due to Candida albicans infections by using the tail vein injection method so as to provide experimental basis for further study of the emergence ,de‐velopment ,prevention ,and treatment of the disease in human beings .METHODS A total of 48 clean male Wister rats were randomly divided six groups ,with 8 rats in each group .The control group was given tail vein injection of 1ml/kg of normal saline ,while the rest of five groups received the tail vein injection of 1 ml/kg of C .albicans liq‐uid （with the concentration of 4×10^8 colony forming units/L） so as to result in severe sepsis .The blood speci‐mens were collected for detection of biochemical indicators at 6 ,12 ,24 ,36 ,and 48 hours ;the histopathologic changes of the livers ,hearts ,lungs ,and kidneys of the rats were observed .RESULTS There was significant differ‐ence in the white blood cells ,biochemical indicators ,aspartate aminotransferase ,urea ,or creatinine between the treatment groups and the control group .The white blood cells began to decrease at 6 hours ,reached the minimum level at 24 hours ,and then elevated;the aspartate aminotransferase began to increase at 6 hours ,significantly in‐creased at 12 hours ,and reached the peak at 24 hours ,and then declined;the urea and creatinine did not change significantly at 6 and 12 hours ,elevated substantially at 24 hours ,and reached the peak at 48 hours .The patholog‐ical examination showed that multiple organs of the rates were remarkably damaged .CONCLUSION The tail vein in‐jection of C .albicans liquid can result in the broad inflammation inside the rats′bodies ,accompanied by damage of multi‐ple organs ,which conforms to the standards and characteristics of the severe sepsis .The study successfully establishes the animal model of sepsis due to C .albicans infections ,which lays the foundation for the study of fungal sepsis .