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大鼠免疫抑制长期模型的建立及验证
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篇名: 大鼠免疫抑制长期模型的建立及验证
TITLE:
摘要: 目的:建立可用于免疫调节剂长期(1个月)药效评价的大鼠免疫抑制长期模型并进行验证实验。方法:以Wistar大鼠为实验动物,以环磷酰胺(CTX)为诱导剂。将大鼠随机分为正常对照组、模型组和治疗组,每组5只。模型组大鼠以35 mg/kg的CTX连续腹腔注射3 d,之后以相同剂量每周腹腔注射1次进行加强诱导,共加强诱导3次,全程31 d;正常对照组大鼠不作任何处理;治疗组大鼠在模型组大鼠建模的基础上,于第3天建模后肌内注射胸腺五肽(TP5)注射液1 mg/kg,隔天注射1次至实验结束。观察整个实验周期内大鼠的精神状况和体质量变化,分别于第4、11、18、25、32天取血,测定外周血中CD4+/CD8+比值。实验结束后处死大鼠,测定其胸腺指数和脾指数。结果:与正常对照组比较,模型组大鼠精神状态较差,体质量增加较缓慢,各时间点的CD4+/CD8+比值和实验结束后的胸腺指数均明显降低,脾指数明显升高,差异均有统计学意义(P<0.05)。与模型组比较,治疗组大鼠精神状态和体质量增加速度均有所改善,第11、25、32天的CD4+/CD8+比值和实验结束后的胸腺指数均明显升高,脾指数明显降低,差异均有统计学意义(P<0.05)。结论:成功建立大鼠免疫抑制长期模型,该模型免疫抑制程度适中,可用于免疫调节剂1个月内的药效评价。
ABSTRACT: OBJECTIVE: To establish a long-term immunosuppressive rat model for immunomodulator long-term pharmacodynamic evaluation (1 month). METHODS: Wistar rats were selected as experimental animal and cyclophosphamide (CTX) was selected as an inducer. Rats were randomly divided into normal control group, model group and treatment group, with 5 rats in each group. Model group was given 35 mg/kg CTX intraperitoneally for consecutive 3 d, and then given same dose once a week to induce model, 3 times in total, for 31 d. Normal control group was not given any treatment. Treatment group was additionally given Thymopentin (TP5) injection 1 mg/kg at third day after modeling, every other day, till the end of experiment, on the basis of model group. The changes of mental status and body weight were observed during the whole experimental period. Blood samples were collected at 4th, 11th, 18th, 25th, 32th day, and CD4+/CD8+ ratio of peripheral blood was determined. Rats were sacrificed after experiment, and thymus index and spleen index were measured. RESULTS: Compared with normal control group, mental state of the rats in the model group was poor and the body weight increased slowly; CD4+/CD8+ ratio at different time points and thymus index after experiment were decreased significantly in model group, while spleen index increased significantly, with statistical significance (P<0.05). Compared with model group, mental state of the rats and the increase of body weight were all improved in treatment group. CD4+/CD8+ ratio at 11th, 25th, 32th day and thymus index after experiment were increased significantly, while spleen index was decreased significantly, with statistical significance (P<0.05). CONCLUSIONS: The long-term immunosuppressive rat model is established successfully. The immunosuppressive level of the model is middle, and it can be used for pharmacodynamic evaluation of immunomodulator within 1 month.
期刊: 2018年第29卷第15期
编辑: 马盼盼,叶军,杨艳芳,张星,王洪亮,刘玉玲
AUTHORS: MA Panpan,YE Jun,YANG Yanfang,ZHANG Xing,WANG Hongliang,LIU Yuling
关键字: 免疫抑制;长期模型;环磷酰胺;胸腺五肽;免疫调节剂;药效学;大鼠
KEYWORDS: Immunosuppression; Long-term model; Cyclophosphamide; Thymopentin; Immunomodulator; Pharmacodynamics; Rats
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