Study on immunomodulatory effect of Guipi pills on D-galactose-induced aging mice

LI Sixiao; YUAN Guangxin; MA Yue; WANG Yutong

doi:10.6039/j.issn.1001-0408.2023.12.04

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Study on immunomodulatory effect of Guipi pills on D-galactose-induced aging mice

更新时间：2025-09-27

- Study on immunomodulatory effect of Guipi pills on D-galactose-induced aging mice
- ZHONGGUO YAOFANG Vol. 34, Issue 12, Pages: 1426-1430(2023)
- 作者机构：
  
  北华大学药学院，吉林吉林　132013
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.12.04
  CLC： R965
- Received：13 November 2022，
  
  Revised：2023-05-10，
  
  Accepted：12 May 2023，
  
  Published：30 June 2023
- 稿件说明：
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李思晓,苑广信,马月,等.归脾丸对D-半乳糖致衰老小鼠的免疫调节作用研究[J].中国药房,2023,34(12):1426-1430.

LI Sixiao,YUAN Guangxin,MA Yue,et al.Study on immunomodulatory effect of Guipi pills on D-galactose-induced aging mice[J].ZHONGGUO YAOFANG,2023,34(12):1426-1430.
李思晓,苑广信,马月,等.归脾丸对D-半乳糖致衰老小鼠的免疫调节作用研究[J].中国药房,2023,34(12):1426-1430. DOI： 10.6039/j.issn.1001-0408.2023.12.04.

LI Sixiao,YUAN Guangxin,MA Yue,et al.Study on immunomodulatory effect of Guipi pills on D-galactose-induced aging mice[J].ZHONGGUO YAOFANG,2023,34(12):1426-1430. DOI： 10.6039/j.issn.1001-0408.2023.12.04.

摘要

目的

研究归脾丸对D-半乳糖（D-gal）致衰老小鼠的免疫调节作用。

方法

运用网络药理学方法筛选归脾丸发挥免疫作用的相关靶点和相关通路，并通过药效学实验进行验证。将105只雄性ICR小鼠随机分为空白对照（CON）组、模型对照（MOD）组、阳性对照（POS）组、归脾丸低剂量（GD）组和归脾丸高剂量（GG）组，除CON组皮下注射生理盐水外，其余各组小鼠皮下注射400 mg/kg D-gal以复制衰老模型；CON组与MOD组灌胃蒸馏水，POS组灌胃300 mg/kg匹多莫德口服溶液，GD组和GG组分别灌胃300 mg/kg和600 mg/kg的归脾丸水溶液，每日1次，共计8周。给药结束后，采集血清及脾脏组织，检测小鼠血清中白细胞介素2（IL-2）、IL-4、IL-6、肿瘤坏死因子α（TNF-α）的含量以及免疫球蛋白G（IgG）、IgM和IgA含量；计算脾脏指数并观察脾脏组织病理学改变；检测小鼠脾脏组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）活性和8-羟基脱氧鸟苷（8-OHdG）含量；检测除POS组外小鼠脾脏组织中TNF/磷酸肌醇-3-激酶-蛋白激酶B（PI3k-Akt）途径中相关蛋白的表达情况。

结果

网络药理学分析结果显示，TNF、IL-6、Akt1为核心靶点。药效学研究结果显示，与MOD组比较，归脾丸各剂量组小鼠血清中IL-2、IL-4、IgG、IgM、IgA含量均显著升高，TNF-α、IL-6含量均显著降低，脾脏指数均显著升高（

＜0.05或

＜0.01）；淋巴细胞弥漫性增生的现象改善，脾细胞紧密排列，白髓和红髓之间界线清晰；脾脏组织中SOD、GSH-Px活性均显著升高，MDA活性和8-OHdG含量均显著降低，TNF-α、PI3K、p-Akt蛋白表达水平均显著降低（

＜0.05或

＜0.01）。

结论

归脾丸能够调节D-gal致衰老小鼠的免疫功能，其作用可能与调控TNF/PI3k-Akt途径进而减轻小鼠脾脏组织氧化应激损伤以及调节TNF-α、PI3K、p-Akt蛋白水平的表达有关。

Abstract

OBJECTIVE

To study the immunomodulatory effect of Guipi pills on D-galactose（D-gal）-induced aging mice.

METHODS

The immune-related targets and related pathways for Guipi pills to exert immune effects were screened by network pharmacology and verified through pharmacodynamic experiments. Totally 105 male ICR mice were randomly divided into blank control （CON） group， model control （MOD） group， positive control （POS） group， Guipi pills low-dose （GD） group and Guipi pills high-dose （GG） group. Except for the CON group， other groups were subcutaneously injected with 400 mg/kg D-gal to induce the aging model； CON group and MOD group were given distilled water， POS group was given 300 mg/kg pidotimod oral solution intragastrically， GD group and GG group were given Guipi pills 300， 600 mg/kg intragastrically， once a day， for 8 weeks. After medication， the serum and spleen were collected， and the contents of interleukin 2 （IL-2）， IL-4， IL-6 and tumor necrosis factor α （TNF-α）， and the contents of immunoglobulin G （IgG）， IgM and IgA were detected. The spleen index was calculated and the histopathological changes in the spleen were observed. The activities of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and malondialdehyde （MDA）， and the content of 8-hydroxy-2 deoxyguanosine （8-OHdG） in spleen were detected； the expression of TNF/phosphoinositide-3-kinase-threonine protein kinase （PI3k-Akt）-related proteins in spleen was detected except for POS group.

RESULTS

The results of network pharmacology showed that TNF， IL-6 and Akt1 were core targets. The results of pharmacodynamic study showed that compared with MOD group， the contents of IL-2， IL-4， IgG， IgM and IgA were increased significantly in Guipi pills groups， while the contents of TNF-α and IL-6 were decreased significantly； the spleen index was increased significantly （

＜0.05 or

＜0.01）. The phenomenon of diffuse proliferation of lymphocytes was improved， the spleen cells were closely arranged， and the line between the white pulp and red pulp was clear. The activities of SOD and GSH-Px in spleen were increased significantly， while the activity of MDA， the content of 8-OHdG， and the protein expressions of TNF-α， PI3K and p-Akt were decreased significantly （

＜0.05 o

＜0.01）.

CONCLUSIONS

Guipi pills can regulate the immune function of D-gal-induced aging mice， which is related to regulating the TNF/PI3k-Akt pathway， thereby reducing oxidative stress damage in spleen tissue of mice， and regulating protein expressions of TNF-α， PI3K and p-Akt.

关键词

Keywords

references

孙晓康，张艳艳，张晓元，等 . 衰老机制及抗衰老治疗的研究进展 [J ] . 食品与药品， 2022 ， 24 （ 1 ）： 74 - 80 .

GUBBELS BUPP M R ， POTLURI T ， FINK A L ， et al . The confluence of sex hormones and aging on immunity [J ] . Front Immunol ， 2018 ， 9 ： 1269 .

何源，王露露，张晶 . 多糖抗衰老作用机制的研究进展 [J ] . 中成药， 2022 ， 44 （ 2 ）： 528 - 531 .

VALLET H ， FALI T ， SAUCE D . Aging of the immune system：from fundamental to clinical data [J ] . Rev Med Interne ， 2019 ， 40 （ 2 ）： 105 - 111 .

王世宏，孙永明 . 归脾丸、复方阿胶浆治疗白细胞减少症27例临床观察 [J ] . 中成药， 1999 ， 21 （ 8 ）： 414 - 415 .

高晓英 . 人参归脾丸治疗室性早搏临床分析 [J ] . 中外医疗， 2009 ， 28 （ 14 ）： 107 .

勇晓，李美香 . 归脾丸佐治内镜阴性胃食管反流病30例分析 [J ] . 中华临床新医学， 2004 ， 4 （ 1 ）： 86 .

孟瑶 . 基于网络药理学和分子对接探讨茵陈四逆汤治疗肝损伤的潜在作用机制 [D ] . 长春：吉林大学， 2022 .

RU J L ， LI P ， WANG J N ， et al . TCMSP：a database of systems pharmacology for drug discovery from herbal medicines [J ] . J Cheminform ， 2014 ， 6 ： 13 .

DING F ， LUO X ， TU Y T ， et al . Alpk1 sensitizes pan-creatic beta cells to cytokine-induced apoptosis via upregulating TNF-α signaling pathway [J ] . Front Immunol ， 2021 ， 12 ： 705751 .

HE J ， ZHANG N H ， ZHU Y ， et al . MSC spheroids-loaded collagen hydrogels simultaneously promote neuronal differentiation and suppress inflammatory reaction through PI3K-Akt signaling pathway [J ] . Biomaterials ， 2021 ， 265 ： 120448 .

SCHULTE W ， BERNHAGEN J ， BUCALA R . Cytokines in sepsis：potent immunoregulators and potential therapeutic targets：an updated view [J ] . Mediators Inflamm ， 2013 ， 2013 ： 165974 .

WU Y N ， YAN F F ， HU J Y ， et al . The effect of chronic ammonia exposure on acute-phase proteins，immunoglobulin，and cytokines in laying hens [J ] . Poult Sci ， 2017 ， 96 （ 6 ）： 1524 - 1530 .

DE LA FUENTE M ， MIQUEL J . An update of the oxidation-inflammation theory of aging：the involvement of the immune system in oxi-inflamm-aging [J ] . Curr Pharm Des ， 2009 ， 15 （ 26 ）： 3003 - 3026 .

LEE S ， KIM M S ， LEE D ， et al . The comparative immunotoxicity of mesoporous silica nanoparticles and colloidal silica nanoparticles in mice [J ] . Int J Nanomedicine ， 2013 ， 8 ： 147 - 158 .

STRAUB R H . Complexity of the bi-directional neuroimmune junction in the spleen [J ] . Trends Pharmacol Sci ， 2004 ， 25 （ 12 ）： 640 - 646 .

GUO X J ， ZHANG J Y ， LIU M ， et al . Protective effect of ginsenoside Rg1 on attenuating anti-GBM glomerular nephritis by activating NRF2 signalling [J ] . Artif Cells Nanomed Biotechnol ， 2019 ， 47 （ 1 ）： 2972 - 2979 .

ZHAO Y B ， XIAO Y ， XIE Y M . Clinical study on changes of serum levels of immunoglobulin and cytokines in anaphylaxis patients induced by Qingkailing injection [J ] . Zhongguo Zhong Yao Za Zhi ， 2011 ， 36 （ 10 ）： 1382 - 1385 .

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