鲜枸杞子提取物通过p38 MAPK信号通路抑制人肝癌细胞HepG2诱导小鼠恶病质的作用及机制

刘婷; 丁艳; 杨婷婷; 马晓娜; 金毅然; 马海滨; 梁雪云

doi:10.13422/j.cnki.syfjx.20190924

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鲜枸杞子提取物通过p38 MAPK信号通路抑制人肝癌细胞HepG2诱导小鼠恶病质的作用及机制

药理 | 更新时间：2021-02-09

- 鲜枸杞子提取物通过p38 MAPK信号通路抑制人肝癌细胞HepG2诱导小鼠恶病质的作用及机制
- Effect and Mechanisms of Lycii Fructus on Hepatoma HepG2 Cell Line-induced Cachexia in Mice
- 中国实验方剂学杂志 2019年25卷第9期页码：89-94
- 作者机构：
  
  1.宁夏医科大学总医院　宁夏人类干细胞研究所，银川　 750004
  2.宁夏医科大学　总医院，银川　 750004
- 作者简介：
  
  刘婷，硕士，助理研究员，从事肿瘤生物学研究，E-mail：25856262@qq.com
  梁雪云，博士，副研究员，从事细胞生物学研究，E-mail：706977918@qq.com
- 基金信息：
  
  宁夏自然科学基金项目(NZ16168)
- DOI：10.13422/j.cnki.syfjx.20190924
  中图分类号： R22; R242; R2-031; R285.5
- 收稿日期：2019-01-09，
  
  网络出版日期：2019-01-18，
  
  纸质出版日期：2019-05-05
- 稿件说明：
移动端阅览
刘婷, 丁艳, 杨婷婷, 等. 鲜枸杞子提取物通过p38 MAPK信号通路抑制人肝癌细胞HepG2诱导小鼠恶病质的作用及机制[J]. 中国实验方剂学杂志, 2019,25(9):89-94.

Ting LIU, Yan DING, Ting-ting YANG, et al. Effect and Mechanisms of Lycii Fructus on Hepatoma HepG2 Cell Line-induced Cachexia in Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 89-94.
刘婷, 丁艳, 杨婷婷, 等. 鲜枸杞子提取物通过p38 MAPK信号通路抑制人肝癌细胞HepG2诱导小鼠恶病质的作用及机制[J]. 中国实验方剂学杂志, 2019,25(9):89-94. DOI： 10.13422/j.cnki.syfjx.20190924.

Ting LIU, Yan DING, Ting-ting YANG, et al. Effect and Mechanisms of Lycii Fructus on Hepatoma HepG2 Cell Line-induced Cachexia in Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 89-94. DOI： 10.13422/j.cnki.syfjx.20190924.

摘要

目的：

探讨鲜枸杞子提取物(LBL)对人类肝癌细胞系HepG2诱导的小鼠恶病质模型的作用及其相关机制研究。

方法：

小鼠分为正常组，恶病质模型组，LBL低剂量组(LBL 5 mg·kg

－1

)，LBL高剂量组(LBL 25 mg·kg

－1

)。采用人肝癌细胞系HepG2成功建立小鼠恶病质模型，待小鼠的体质量明显下降时，连续灌喂生理盐水或不同剂量LBL 28 d后，记录各组小鼠的体质量，酶联免疫吸附测定(enzyme linked immunosorbent assay

ELISA)检测血浆肌酸激酶(creatine kinase

CK)，促炎因子白细胞介素-1

(interleukin-1

，IL-1

)，白细胞介素-6(interleukin-6，IL-6)，肿瘤坏死因子-

(tumor necrosis factor-

，TNF-

)的水平，采用免疫组织化学检测小鼠肌肉降解水平及p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase

p38 MAPK)的表达，蛋白免疫印迹法(Western blot)检测磷酸化p38 MAPK(phospho-p38 mitogen-activated protein kinase

p-p38 MAPK)，炎症信号通路核转录因子-

B(nuclear factor

NF-

B)的表达。

结果：

与恶病质模型组比较，LBL低、高剂量组小鼠体质量明显下降(

0.05，

0.01)，肌肉降解程度明显抑制(

0.05)，CK水平显著下降(

0.01)；LBL低、高剂量组小鼠血浆IL-1

，IL-6，TNF-

表达水平明显下调(

0.05，

0.01)。免疫组织化学结果显示，LBL低、高剂量组p38 MAPK蛋白表达降低(

0.05)，Western blot结果进一步证实p-p38 MAPK

NF-

B蛋白表达降低(

0.01)。与LBL低剂量组比较，LBL高剂量组血浆肌酸激酶，p38 MAPK

p-p38 MAPK

NF-

B蛋白表达明显降低(

0.05，

0.01)。

结论：

鲜枸杞子提取物能够抑制人类肝癌细胞系HepG2诱导的小鼠恶病质模型的恶病质的进程，其作用机制可能与其下调促炎因子IL-1

，IL-6，TNF-

，从而抑制p38 MAPK

p-p38 MAPK

NF-

B的表达相关。

Abstract

Objective:

To investigate the inhibitory effect and mechanism of the extracts from fresh Lycii Fructus(LBL) on hepatoma HepG2 cell-induced cachexia in mouse.

Method:

The human hepatoma cell line HepG2 was injected into BALB/C mice to establish the cachexia model. Then the LBL was fed to the models respectively in low dose (5 mg·kg

-1

) or high dose (25 mg·kg

-1

). After 28 days of continuous feeding

the mice's body weight was detected. The expression levels of creatine kinase (CK)

interleukin-1

(IL-1

)

interleukin-6 (IL-6) and tumor necrosis factor-

(TNF-

) were evaluated by enzyme linked immunosorbent assay (ELISA). The muscle degradation and the expression of p38 mitogen-activated protein kinase (p38 MAPK) were detected by immunohistochemistry staining. The expression levels of phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-

B (NF-

B) were determined by Western blot.

Result:

Compared with cachexia group

the loss of body weight and muscle decomposition were significantly inhibited both in the low dose LBL group and high dose LBL group(

0.05

0.01). The level of plasma CK decreased significantly both in the low-dose LBL group and the high-dose LBL group (

0.01). ELISA tests revealed lower expression levels of IL-1

IL-6 and TNF-

in both the low-dose LBL group and the high-dose LBL group (

0.05

0.01). Immunohistochemistry staining showed that the expression of p38 MAPK was inhibited both in the low-dose LBL group and the high-dose LBL group (

0.05). Western blot indicated that the expressions of p-p38 MAPK and NF-

B were inhibited both in the low-dose LBL group and the high-dose LBL group (

0.01). We found that the high-dose LBL group shows a higher inhibitory capability than the low-dose LBL group.

Conclusion:

LBL could inhibit the cachexia induced by hepatoma HepG2 cell line in mouse

suggesting LBL could reduce major cytokine and plasma inflammatory factors through p-p38 MAPK pathway.

关键词

Keywords

references

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