【作者】 申红霞；

【导师】 王蕾； 孙伟；

【作者基本信息】 青岛大学 ， 药理学， 2008， 硕士

【摘要】 目的:研究牛磺酸（taurine,Tau）对环磷酰胺（cyclophosphamide,CTX）增效减毒的作用。方法:取健康昆明小鼠50只,将H₂₂肿瘤细胞种植于小鼠右腋窝皮下,建立移植性肿瘤模型。实验分为五组:模型对照组,CTX(20mg·kg^-1)对照组,CTX(20mg·kg^-1)+Tau低剂量(50mg·kg^-1)组,CTX(20mg·kg^-1)+Tau中剂量组(100mg.kg^-1),CTX(20mg·kg^-1)+Tau高剂量(200mg·kg^-1)组。腹腔注射给药,每同1次,连续8d。观察不同剂量Tau与CTX联合用药的抑瘤率,脾指数和胸腺指数;检测骨髓有核细胞数和外周血白细胞数;MTT法检测NK细胞杀伤活性和脾淋巴细胞增殖率。S₁₈₀肿瘤模型的建立与处置同H₂₂肿瘤模型。结果:H₂₂荷瘤小鼠:①CTX组抑瘤率为50.32%;.Tau+CTX低、中、高剂量组的抑瘤率分别为58.06%,67.74%,72.26%,具有量效关系。②与模型对照组比较,CTX组骨髓有核细胞和外周血白细胞水平降低（P<0.01,P<0.01）;与CTX组比较,Tau+CTX组骨髓有核细胞和外周血白细胞水平升高（P<0.05,P<0.01）。③CTX组脾指数和胸腺指数与模型组比较均下降（P<0.05,P<0.01）,而Tau+CTX剂量组与CTX组比较,脏器指数升高,差异有显著性（P<0.05,P<0.01）。④CTX组与模型组比较,NK细胞活性下降（P<0.05）;Tau+CTX中、高剂量组与CTX组比较,NK细胞活性升高（P<0.01,P<0.01）。⑤CTX组T、B淋巴细胞增殖与模型组无差别;Tau+CTX组T、B淋巴细胞增殖与CTX组比较,活性升高（P<0.05,P<0.01）。S₁₈₀荷瘤小鼠:①CTX组抑瘤率为56.65%;Tau+CTX低、中、高剂量组的抑瘤率分别为60.10%,72.41%,86.70%,具有量效关系。②CTX组骨髓有核细胞和外周血白细胞水平低于模型对照组（P<0.01,P<0.01）;Tau+CTX中、高剂量组骨髓有核细胞和外周血白细胞水平高于CTX组（P<0.05,P<0.01）。③与模型组比较,CTX组脾指数和胸腺指数均下降（P<0.05,P<0.05）,而Tau+CTX剂量组与CTX组比较,脏器指数升高,差异有显著性（P<0.05,P<0.01）。④CTX组与模型组比较,NK细胞活性下降（P<0.05）;Tau+CTX中、高剂量组与CTX组比较,NK细胞活性升高（P<0.01,P<0.05）。⑤CTX组T、B淋巴细胞增殖与模型组无差别;Tau+CTX组T、B淋巴细胞增殖与CTX组比较,活性升高（P<0.05,P<0.01）。结论:牛磺酸与环磷酰胺联合用药具有增效减毒作用。更多还原

【Abstract】 Objective:To investigate synergism and attenuation effect of taurine on CTX.Methods: Fifty Kim Ming healthy mice were given 0.2ml of H₂₂ tumor cell suspension(containing 2×10⁶ cells-ml^-1)at the mice subaxillary region. The mice were randomly divided into five groups: model control group; CTX control group and three trial groups. The model group was given an intraperitoneal injection of sodium chloride; the CTX group was given CTX 20mg·kg^-1; and the three trial groups were given CTX+Tau （20+50） mg·kg^-1,（20+100） mg·kg^-1and （20+200） mg·kg^-1 respectively, q.d. for eight days. The inhibition rate of CTX+Tau and CTX on H₂₂ tumor, the spleen index and the thymus index were observed; The levels of white blood cells（WBC） and bone marrow nucleate cells were measured; The activities of NK cells and lymphocyte proliferation were analyzed by MTT. S₁₈₀ was studied in the same manner as H₂₂.Results: Model of H₂₂ tumor:①The tumor inhibition rate of the CTX group and the three trial groups were 50.32%, 58.06%, 67.74%, and 72.26% respectively.②Compared with the model group, the bone marrow nucleate cells and WBC’s levels of the CTX group decreased significantly （P<0.01,P<0.01）;Compared with the CTX group, the bone marrow cells and WBC’s levels of the Tau +CTX groups increased （P<0.05, P<0.01）.③Compared with the model group, spleen index and thymus index of the CTX group decreased （P<0.05, P<0.01）, while compared with the CTX group, spleen index and thymus index of the Tau+CTX groups were improved and the difference was significant （P<0.05, P<0.01）.④Compared with the model group, NK cell activity of the CTX group decreased （P<0.05）;NK cell activity of Tau+CTX groups（the mudium,high-dose groups）were higher than the CTX group（P<0.05, P<0.01）.⑤Compared with the model group, T and B lymphocyte proliferation activity of the CTX group had no obvious difference; Compared with the CTX group, T and B lymphocyte proliferation activity of the Tau+CTX groups increased （P<0.05, P<0.01）. Model of S₁₈₀ tumor:①The tumor inhibition rate of the CTX group and the three trial groups were 56.65%, 60.10%, 72.41%, and 86.70% respectively.②Compared with the model group, the bone marrow nucleate cells and WBC’s levels of the CTX group decreased significantly （P<0.01, P<0.01）; Compared with the CTX group, the bone marrow cells and WBC’s levels of the Tau +CTX groups（the mudium,high-dose groups） increased （P<0.05, P<0.01）.③Compared with the model group, spleen index and thymus index of the CTX group decreased （P0.05, P<0.05）, while compared with the CTX group, spleen index and thymus index of the Tau+CTX groups were improved （P<0.05, P<0.01）.④Compared with the model group, NK cell activity of the CTX group decreased （P<0.05）; NK cell activity of Tau+CTX groups（the mudium,high-dose groups）were higher than the CTX group（P<0.05, P<0.01）.⑤Compared with the model group, T and B lymphocyte proliferation activity of the CTX group had no obvious difference; Compared with the CTX group, T and B lymphocyte proliferation activity of the Tau+CTX groups increased （P<0.05, P<0.01）.更多还原