牛磺酸对环磷酰胺的增效减毒作用研究
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H_(22)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。S_(180)肿瘤模型的建立与处置同H_(22)肿瘤模型。
结果:H_(22)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)。
S_(180)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。
Objective:To investigate synergism and attenuation effect of taurine on CTX.
Methods: Fifty Kim Ming healthy mice were given 0.2ml of H_(22) tumor cell suspension(containing 2×10~6 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~(-1)and (20+200) mg·kg~(-1) respectively, q.d. for eight days. The inhibition rate of CTX+Tau and CTX on H_(22) 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. S_(180) was studied in the same manner as H_(22).
Results: Model of H_(22) 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 S_(180) 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).
方法:取健康昆明小鼠50只,将H_(22)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。S_(180)肿瘤模型的建立与处置同H_(22)肿瘤模型。
结果:H_(22)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)。
S_(180)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。
Objective:To investigate synergism and attenuation effect of taurine on CTX.
Methods: Fifty Kim Ming healthy mice were given 0.2ml of H_(22) tumor cell suspension(containing 2×10~6 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~(-1)and (20+200) mg·kg~(-1) respectively, q.d. for eight days. The inhibition rate of CTX+Tau and CTX on H_(22) 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. S_(180) was studied in the same manner as H_(22).
Results: Model of H_(22) 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 S_(180) 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).
引文
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