Effect of Yiqi Jianpi Huayu Recipe Combined with 5-FU on Growth and Immune Function of Subcutaneous Transplanted Tumor in MFC Bearing Mice

Min WANG; Shen-lin LIU; Jian WU; Hai-dan WANG; Qing-min SUN; Bai YE

doi:10.13422/j.cnki.syfjx.20190521

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Effect of Yiqi Jianpi Huayu Recipe Combined with 5-FU on Growth and Immune Function of Subcutaneous Transplanted Tumor in MFC Bearing Mice

Pharmacology | 更新时间：2021-02-09

- Effect of Yiqi Jianpi Huayu Recipe Combined with 5-FU on Growth and Immune Function of Subcutaneous Transplanted Tumor in MFC Bearing Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 6, Pages: 65-72(2019)
- 作者机构：
  
  南京中医药大学　附属医院，南京　 210029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190521
  CLC： R22;R242;R2-031;R285.5;R273
- Received：28 July 2018，
  
  Published Online：2018-20-11，
  
  Published：20 March 2019
- 稿件说明：
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Min WANG, Shen-lin LIU, Jian WU, et al. Effect of Yiqi Jianpi Huayu Recipe Combined with 5-FU on Growth and Immune Function of Subcutaneous Transplanted Tumor in MFC Bearing Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(6): 65-72.
DOI：

Min WANG, Shen-lin LIU, Jian WU, et al. Effect of Yiqi Jianpi Huayu Recipe Combined with 5-FU on Growth and Immune Function of Subcutaneous Transplanted Tumor in MFC Bearing Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(6): 65-72. DOI： 10.13422/j.cnki.syfjx.20190521.

摘要

目的：

探讨益气健脾化瘀方联合5-氟尿嘧啶(5-FU)对MFC荷瘤615小鼠皮下移植瘤的生长及免疫功能的影响。

方法：

24只615小鼠随机分为模型组，益气健脾化瘀方（20 g·kg

－1

）组，5-FU（25 mg·kg

－1

）组，联合（益气健脾化瘀方20 g·kg

－1

＋5-FU 25 mg·kg

－1

）组，每组6只，皮下接种法建立小鼠胃癌移植瘤模型。于末次给药后完整剥离移植瘤、脾、胸腺，计算抑瘤率、胸腺、脾指数。流式细胞仪测定外周血、肿瘤组织中髓源抑制性细胞（MDSC）水平及其亚型多形核细胞样（PMN-MDSC），单核细胞样（M-MDSC）的水平及外周血中各免疫细胞的水平；实时荧光定量PCR（Real-time PCR）检测瘤组织中精氨酸酶-1（Arg-1），诱导型一氧化氮合酶（iNOS）mRNA表达水平。

结果：

与模型组比较，益气健脾化瘀方组小鼠体质量增加、瘤重减轻，5-FU组小鼠体质量、瘤重、胸腺、脾指数均下降(

0.05

0.01)。与5-FU组比较，联合组体质量增加，瘤重减轻，胸腺、脾指数升高(

0.05

0.01)。与模型组比较，联合组肿瘤组织及外周血中总MDSCs水平下降(

0.05

0.01)，益气健脾化瘀方组，5-FU组及联合组PMN-MDSC水平均下降(

0.01)；与5-FU组比较，联合组PMN-MDSC水平下降(

0.05)

M-MDSC水平下降(

0.05)。与模型组比较，益气健脾化瘀方组巨噬细胞及其M1型水平增加(

0.05)，各T细胞群水平均增加(

0.05

0.01)，5-FU组巨噬细胞，CD3

＋

，CD4

＋

，CD8

＋

T细胞群水平下降(

0.05

0.01)。与5-FU组比较，联合组巨噬细胞，CD4

＋

，CD8

＋

T细胞群水平增高(

0.01)。与模型组比较，各组iNOS，Arg-1 mRNA表达均下降(

0.05

0.01)。与5-FU组比较，联合组iNOS，Arg-1 mRNA表达均下降(

0.05

0.01)。

结论：

益气健脾化瘀方对肿瘤有一定的抑制作用，且与5-FU联合使用能更好地抑制皮下移植瘤的生长，并改善化疗后机体的免疫状态，其机制可能与降低MDSCs的水平及增加T细胞、巨噬细胞的水平有关。

Abstract

Objective:

To discuss the effect of Yiqi Jianpi Huayu recipe (YQJPHY) combined with 5-fluorouracil(5-FU) on the growth and immune function of subcutaneous transplanted tumor in MFC tumor bearing 615 mice.

Method:

Twenty-four mice were inoculated subcutaneously to establish the transplanted tumor model of gastric cancer in mice

and then randomly divided into model control group

YQJPHY (20 g·kg

-1

)group

5-FU (25 mg·kg

-1

) group and (YQJPHY+ 5-FU) combined group

with 6 rats in each group. After the last administration

the transplanted tumor

spleen and thymus were stripped completely. The tumor inhibition rate

thymus and spleen index were calculated. Flow cytometry was used to determine the content of myeloid-derived suppressor cells (MDSCs) and its subtype polykaryotype cells (PMN-MDSC)

single karyotype cells (M-MDSC) in both peripheral blood and tumor tissue

and macrophages and their M1 type

M2 type

T lymphocyte

B lymphocyte

and natural killer cells (NK cells) in peripheral blood. Expressions of arginase-1(Arg-1) and inducible nitric oxide synthesis (iNOS) gene in tumor tissues were detected by Real-time PCR.

Result:

Compared with model control group

the weight of mice in YQJPHY group increased

whereas the weight of tumor

the weight of tumor

the index of thymus and spleen decreased in 5-FU group(

0.05

0.01). Compared with 5-FU group

combined group showed gained weight

decreased tumor weight

and increased thymus and spleen index(

0.05

0.01). Compared with model control group

the total MDSCs content in tumor tissue and peripheral blood of the combined group was decreased

and the PMN-MDSC content in 5-FU group and the combined group were decreased(

0.05

0.01). Compared with 5-FU group

the contents of total MDSCs

PMN-MDSC

M-MDSC in combined group were all decreased(

0.05

0.01). Compared with model control group

the number of macrophages and their M1 type in YQJPHY group were higher than those in 5-FU group

while the contents of CD3

CD4

CD8

T cell group decreased(

0.05

0.01). Compared with model control group

gene expressions of iNOS

Arg-1 decreased in all groups(

0.05

0.01). Compared with 5-FU group

gene expressions of iNOS

Arg-1 decreased in combined group(

0.05

0.01).

Conclusion:

YQJPHY can better inhibit the growth of subcutaneous transplanted tumor when combined with 5-FU

and improve immune status after chemotherapy. The mechanism may be related to the decrease of MDSCs content and the increase of T cell and macrophages content.

关键词

Keywords

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