中文摘要

中文摘要

目的： 通过观察裴氏升血颗粒(PG)对5-氟尿嘧啶(5-Fu)化疗后荷瘤小鼠肿瘤生长情况、免疫器官指数及T细胞亚群和IL-2的影响，探讨该颗粒增效减毒的作用及机理。

方法： 建立荷H₂₂(肝癌)瘤小鼠模型后，将50只小鼠随机分为5组：模型组、5-Fu组和裴氏升血颗粒小、中、大剂量联合5-Fu组，每组10只。造模次日除模型组给予蒸馏水外其余各组开始进行药物干预，共10天。停药次日眼球取血处死小鼠，用瘤体重量计算裴氏升血颗粒联合5-Fu对荷瘤小鼠抑瘤率的影响；胸腺、脾脏称重计算胸腺指数(TI)和脾脏指数(SI)；用流式细胞仪检测小鼠外周血中CD3⁺、CD4⁺、CD8⁺的量及用放免法检测小鼠血清中IL-2的含量。

结果： 动物实验表明：(1)裴氏升血颗粒联合5-Fu组抑瘤率较5-Fu组明显提高，其中PG大剂量+5-Fu组的抑瘤率为72.4%。(2)裴氏升血颗粒小、中、大剂量+5-Fu组荷瘤小鼠胸腺指数及脾脏指数均高于5-Fu组，PG大剂量+5-Fu组胸腺指数14.2mg/10g、脾脏指数为52.4mg/10g，统计学意义显著。(3)裴氏升血颗粒小、中、大剂量+5-Fu组CD3⁺、CD4⁺和CD4⁺/CD8⁺均升高，CD8⁺降低；其中CD4⁺/CD8⁺的比值分别是：5.9、6.4、5.2，与5-Fu组相比具有统计学意义(p<0.05)。(4)裴氏升血颗粒中剂量+5-Fu组IL-2的含量为1.18ng/mL，较5-Fu组显著升高(p<0.05)。

结论： 裴氏升血颗粒联合5-Fu对荷H₂₂瘤小鼠具有明显增效减毒作用。增效作用主要反映在抑瘤率的提高，以裴氏升血颗粒大剂量+5-Fu组作用最为明显；减毒作用反映于CD3⁺、CD4⁺及IL-2的量增加，CD8⁺的量减少，以裴氏升血颗粒中剂量+5-Fu组作用最为明显。裴氏升血颗粒通过调节荷H₂₂瘤小鼠机体的免疫功能，改善机体的反应性，从而达到增效减毒的作用。

关键词： 裴氏升血颗粒；抑瘤率；胸腺指数；脾脏指数；T细胞亚群；IL-2

裴正学系列方药的研究

ABSTRACT

Objective: To investigate the function and mechanism of Peishishengxue Granule (PG) on enhancing efficacy and reducing toxicity through observing the PG combined with 5-Fu on the weights of solid tumor and the immune organs, the levels of T-cell subgroups and Interleukin-2 (IL-2) in H22 bearing mice.

Methods: The fifty models of solid tumor by hepatoma cell H22 transplantation in mice were divided into five groups: model group, 5-Fu group, PG low, medium and high dose combined with 5-Fu groups. There were ten mice in each group. The next day, except the model group the rest groups were dealt with drug-intervention, once a day for ten days. After that, all mice were killed, and the weights of solid tumor, thymus and spleen were measured, and the tumor inhibiting rates, the thymus index (TI) and the spleen index (SI) were calculated. The levels of CD3、CD4、CD8+ was measured by flow cytometric technique and IL-2 was measured by RIA.

Results: The experiment showed: 1. The tumor inhibiting rates were higher in each PG combined with 5-Fu groups than that in the 5-Fu group and in PG high dose combined with 5-Fu group it was 72.4%; 2. The TI and SI was increased in PG combined with 5-Fu groups. In PG high dose combined with 5-Fu group they were significantly increased, The TI was 14.2mg/10g (p<0.05) and The SI was 52.4mg/10g (p<0.05); 3. The levels of CD3、CD4+、CD4/CD8+ were higher while CD8+ was lower in the three PG combined with 5-Fu groups than those in the 5-Fu groups, and CD4+/CD8+ in PG combined with 5-Fu groups were: 5.9、6.4、5.2 (p<0.05); 4. The levels of IL-2 in PG medium dose combined with 5-Fu group was 1.18ng/ml, it was markedly higher in 5-Fu group (p<0.05).

Conclusion: PG can enhance efficacy and reduce toxicity obviously. Improving the anti-tumor effect of 5-Fu can reflect the enhancing efficacy, especial the PG high dose combined with 5-Fu group. Improving the levels of CD3、CD4 and IL-2 can reflect the reducing toxicity, especial the PG medium dose combined with 5-Fu group. PG can regulate the immune function of tumor-bearing mouse, improve the reaction of economy, consequently it can attain the function of improving the immune function and reducing the adverse reactions of chemotherapy.

KEY WORDS: Peishishengxue Granule; tumor inhibiting rates; SI; TI; the T-cell subgroups; IL-2

裴正学系列方药的研究

前言

裴氏升血颗粒是我国著名中西医结合专家、导师裴正学教授通过长期的临床实践而拟定的治疗血液病的专方，此方主要由六味地黄汤合生脉散加减而成，六味地黄汤以补肾，生脉散以健脾，同时加用太子参、潞党参、北沙参以益气固本。该方于1968年完全彻底治愈了急性单核细胞性白血病（M₅）患者马长生，于1974年在苏州召开的全国血液病会议上被定名为"兰州方"[1]。此方在临床治疗肿瘤及血液病方面疗效显著，1997年该方作为甘肃省医学科学研究院院内制剂，制成"裴氏升血颗粒"。该制剂于2002年起作为甘肃省医学科学研究院临床科研课题进行实验研究，通过了成果鉴定。曾获得2003年甘肃省皇甫谧科技成果一等奖。

裴氏升血颗粒以扶正固本为大法，注重调节机体的反应性，即增强机体的免疫功能，使机体之免疫低下状态得到不同程度的改善，从而达到临床疗效。中医这一"扶正固本"之法，与现代医学之免疫学、分子生物学、基因组学等有着异曲同工之处[2]。

40余年的临床应用，证明裴氏升血颗粒不仅对血液病有很好的疗效，对恶性肿瘤，尤其能改善肿瘤患者放、化疗引起的免疫功能低下状态。临床实践证明该方对食道癌、肝癌、恶性淋巴瘤、再生障碍性贫血等病均有显著疗效。仅据本人在从师侍诊期间的不完全资料统计，该颗粒治愈白血病3例，再生障碍性贫血3例，原发性肝癌3例，胃癌1例、食道癌3例[3-6]。

李氏[7]等运用裴氏升血颗粒配合化疗治疗癌症10例疗效观察显示：从近期疗效看，裴氏升血颗粒组优于单纯化疗组（P<0.05）；从毒副反应看，裴氏升血颗粒组明显轻于单纯化疗组（P<0.01）。邱氏[8]等观察裴氏升血颗粒与核素并用治疗肝癌15例，治疗组用核素加服裴氏升血颗粒，对照组仅用核素，发现治疗组毒副作用明显轻于对照组，二者之疗效对比亦有显著性差异。薛氏[9]运用裴氏升血颗粒治疗原发性肝癌，使患者肿块明显缩小，肝功能完全恢复，提高了患者的生活质量，延长了生存期。

关于裴氏升血颗粒的实验研究，前人亦进行过多方面的动物实验，证明裴氏升血颗粒可改善再障模型小鼠及荷瘤小鼠的免疫功能[10-15]。本文亦是在建立荷H₂₂瘤小鼠模型的基础上，研究裴氏升血颗粒对5-Fu化疗后荷瘤小鼠肿瘤生长情况、免疫器官指数、外周血中CD₃⁺、CD₄⁺、CD₈⁺ T淋巴细胞量及血清中IL-2含量的影响，探讨该颗粒的减毒增效作用及其机理。旨在探索裴氏升血颗粒抗肿瘤的新靶点，为裴氏升血颗粒临床广泛应用提供科学、微观的客观依据。

实验研究