小柴胡汤及其药群配伍抗小鼠H22肝肿瘤及免疫调节作用

目的:观察小柴胡汤及其药群配伍对小鼠H22肝癌实体瘤的抑制作用及对荷瘤小鼠免疫功能的影响,研究小柴胡汤抗肝肿瘤的作用、量效关系及作用机制,探讨小柴胡汤及药群内在配伍意义。方法:建立小鼠H22肝癌模型,分别灌服高、中、低剂量的小柴胡汤煎剂(27,13.5,6.75 g.kg^-1),腹腔注射5-氟尿嘧啶(5-FU)(20mg.kg^-1)做阳性对照;给药10 d后检测各组的瘤重、体重、脾脏和胸腺指数。进一步观察有效剂量(13.5 g.kg^-1)小柴胡汤药群配伍煎剂(柴-芩、姜-夏、参-枣-草、柴-芩+姜-夏、柴-芩+参-枣-草、姜-夏+参-枣-草,全方)对小鼠H22肝癌模型的上述作用。在此基础上,观察小柴胡汤及其有效药群(参-枣-草)对该荷瘤小鼠自然杀伤(NK)细胞、T淋巴细胞增殖及白细胞介素-2(IL-2)的影响。结果:小柴胡汤高、中、低3个剂量组对小鼠H22肝癌实体瘤均有明显抑制作用,抑瘤率分别为49.66%,48.52%,36.91%,药群配伍研究中参-枣-草组和全方组的抑瘤率为41.55%和43.65%。与正常组比,H22荷瘤小鼠脾脏指数显著升高(P<0.001),小柴胡汤高、中、低剂量组和各药群配伍组脾脏指数均明显升高(P<0.01);胸腺指数除全方组外,不同药群配伍组与正常组比均有显著降低(P<0.05),5-FU组有极显著降低(P<0.001);小柴胡汤各组小鼠体重均无明显变化,而5-Fu组小鼠体重下降明显(P<0.001)。与模型组比,小柴胡汤组小鼠NK细胞、T淋巴细胞增殖及IL-2活性均明显升高(P<0.001);参-枣-草组NK细胞和IL-2活性均升高(P<0.05);5-FU组NK细胞、T淋巴细胞增殖及IL-2活性均显著降低(P<0.01)。结论:小柴胡汤及其方中参-枣-草配伍药群有抑制小鼠H22肝癌实体瘤生长和提高荷瘤宿主免疫功能作用,其抑瘤作用机制与5-氟尿嘧啶的直接抑瘤有所不同,可能与增强荷瘤宿主免疫功能有关,提示该方中的扶正作用药群(人参、大枣和甘草)可能是其抑瘤作用的核心药群。

Effect of Xiaochaihu decoction and different herbal formulation of component on inhibiting H22 liver cancer in mice and enhancing immune function

Objective: To observe the effects of Xiaochaihu decoction and different herbal formulation of componenton on inhibiting H22 mouse solid liver cancer and on the immune function,for approaching the dose-effect relationship and compatibility mechanism.Method: Transplanted H22 liver the cancer to mice,filling on high,moderate,low dose of mice in the xiaochaihu decoction drug(27,13.5,6.75 g·kg^-1),5-FU intraperitoneal injection(20 mg·kg^-1) as positive control.After being administered for 10 days,we determined the cancer weight,body weight,spleen index and thymus gland index for studying the dose-effect relationship.And we studied compatibility rule of Xiaochaihu decoction and the different herbal formulations of its components by using the same method.Mice in the Xiaochaihu decoction group(13.5 g·kg^-1) and Ginseng-Chinese Date-Licorice Root apozem group(5 g·kg^-1) were given the medicines for 10 days to observe the weight of tumor,body weight,spleen index,the NK cell activity,proliferation of the T lymphocytes and IL-2 level.Result: Growth of H22 mouse liver cancer was markedly inhibited in high,moderate,low dose group;the inhibiting rates were 49.66%,48.52%,36.91%,respectively;the optimal administration dose was moderate.In the study of compatibility rule,only inhibiting rates of Ginseng-Chinese Date-Licorice Root apozem group and Xiaochaihu decoction group exceed 30%;the inhibiting rates were 41.55% and 43.65%.As compared with normal group,spleen index of three dose groups and the different herbal formulation groups was evidently increased(P<0.01);thymus gland index of the different herbal formulation groups was significant decreased(P<0.05);thymus gland index and body weight of 5-FU group were evidently decreased (P<0.001).As compared the model group,the NK cell activity,proliferation of the T lymphocytes and IL-2 level of Xiaochaihu decoction were remarkably increased(P<0.001);the NK cell activity and IL-2 level of Ginseng-Chinese Date-Licorice Root group were remarkably increased(P<0.05);the NK cell activity and proliferation of the T lymphocytes and IL-2 level of 5-FU group were remarkable decreased(P<0.01).As comparing with the normal control group,body weight of 5-FU group was evidently decreased(P<0.05).Conclusion: Xiaochaihu decoction and Ginseng-Chinese Date-Licorice Root group can markedly inhibit the growth of H22 mouse solid liver cancer and improve the immune function of tumor-bearing mice.The inhibiting effect probably closely related with improving the tumor-bearing host immune function.There is a hint that compatibility Ginseng-Chinese Date-Licorice Root of strengthening body resistance is the core of inhibiting effect.