实验动物与比较医学

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黄芪或其成分治疗急性胰腺炎的动物实验Meta分析

曹星新1, 李艾亦2, 侯婧涵1, 李明学1, 李艳艳1, 靳玮华1, 杨凤梅1, 段素琴1, 和占龙1()   

  1. 1.中国医学科学院/北京协和医学院医学生物学研究所, 昆明 650018
    2.云南大学生命科学学院, 昆明 650091
  • 收稿日期:2025-02-25 修回日期:2025-04-07 出版日期:2025-10-06
  • 作者简介:曹星新(2001—),男,硕士研究生,研究方向:疾病动物模型及药理学。E-mail:s2024018001@student.pumc.edu.cn
    李艾亦(2000—),女,硕士研究生,研究方向:疾病动物模型。E-mail: 15398487968@163.com
    和占龙(1972—),男,博士,研究员,研究方向:疾病动物模型及药物评价。E-mail:hzl@imbcams.com.cn。ORCID: 0000-0001-5379-2521
  • 基金资助:
    国家重点研发计划“大动物微生物与寄生虫质量检测关键技术研究”(2024YFF0728801);云南省基础研究专项-面上项目“小胶质细胞线粒体自噬调控NLRP3炎症小体活化对肠道病毒性脑炎的影响及机制研究”(202401CF070048)

Meta-Analysis of Animal Experiments on Astragali Radix or Its Ingredients for Acute Pancreatitis

CAO Xingxin1, LI Aiyi2, HOU Jinghan1, LI Mingxue1, LI Yanyan1, JIN Weihua1, YANG Fengmei1, DUAN Suqin1, HE Zhanlong1()   

  1. 1.Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650018, China
    2.College of Life Sciences, Yunnan university, Kunming 650091, China
  • Received:2025-02-25 Revised:2025-04-07 Published:2025-10-06
  • Contact: HE Zhanlong (ORCID: 0000-0001-5379-2521), E-mail: hzl@imbcams.com.cn

摘要:

目的 基于系统综述和荟萃分析优先报告条目(Preferred Reporting Items for Systematic Reviews and Meta - Analysis,PRISMA)指南,利用Meta分析(meta-analysis)对文献报告中利用动物实验研究黄芪(纯黄芪制剂)或其成分治疗急性胰腺炎(acute pancreatitis,AP)的药理药效结果进行定量合并,以获得精准可靠的综合效应结论。 方法 检索中国知网(China National Knowledge Infrastructure,CNKI)、维普中文科技期刊数据库(VIP Database for Chinese Technical Periodicals,VIP)、万方数据知识服务平台(Wanfang Data Knowledge Service Platform)、中国生物医学文献数据库(China Biomedical Literature Database,CBMdisc)、PubMed以及 Web of Science(WOS)数据库中从建库初始到2025年3月关于黄芪(纯黄芪制剂)或其成分治疗AP的动物实验相关文献。对于纳入文献使用SYRCLE工具进行偏倚风险评估;对于各研究间的异质性评估遵循Cochrane手册,采用Cochrane's Q检验和I2 统计量进行评价。 结果 本文共检索得到297篇文献,经筛选及评价后最终纳入19项动物实验进行Meta分析。这19篇文献涵盖了SD大鼠、C57BL/6小鼠、BALB/c小鼠和昆明小鼠四个品系,SYRCLE评分为3~4分,Egger's test检验结果为P<0.05,Cochrane's Q检验和I2 统计量显示研究间异质性较大。Meta分析19项动物实验相关文献的结果显示,纯黄芪制剂(黄芪注射液)能降低AP特异性指标血清淀粉酶(serum amylase,AMS)的含量;黄芪成分可以降低AMS与脂肪酶(lipase,LPS)的水平。黄芪注射液或黄芪成分可降低血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1 beta,IL-1β)的水平,升高白细胞介素-10(interleukin-10,IL-10)的水平;升高血清中超氧化物歧化酶(superoxide dismutase,SOD)与谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)的水平,降低丙二醛(malondialdehyde,MDA)的水平。黄芪注射液或黄芪成分的高剂量组相较低剂量组更能降低AMS、TNF-α和IL-6的水平,同时升高SOD的水平,但未证明剂量高低对MDA水平的影响。 结论 动物实验结果的循证学分析显示,在SD大鼠、C57BL/6小鼠、BALB/c小鼠、昆明小鼠等多种动物模型中,黄芪注射液或黄芪成分能有效降低AP特异性指标(AMS、LPS)的表达或分泌水平,其机制可能与部分炎症介质有关,包括降低TNF-α、IL-6和IL-1β的水平,升高IL-10的水平;同时也可能干预氧化/抗氧化平衡过程,如升高SOD和GSH-PX的水平,降低MDA的水平;除MDA外,黄芪注射液或黄芪成分对于降低AMS、TNF-α和IL-6水平以及升高SOD水平呈现剂量相关性。但由于现有研究中存在较高的异质性、一定的发表偏倚风险、动物模型与人类疾病之间的种属差异等问题,未来仍需进一步开展高质量的临床试验或动物实验研究。

关键词: 黄芪, 黄芪注射液, 急性胰腺炎, 动物实验, Meta分析, 大鼠, 小鼠

Abstract:

Objective Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to obtain precise and reliable comprehensive effect conclusions by quantitatively combining pharmacodynamic results from animal experiments investigating Astragali Radix (single-entity Astragali Radix preparation) or its ingredients for treatment of acute pancreatitis (AP) in literature reports through meta-analysis. Methods Databases including CNKI, CSTJ, Wanfang, CBM, PubMed, and Web of Science were searched from inception to March 2025 for animal studies related to Astragali Radix (single-entity Astragali Radix preparation) or its ingredients for AP treatment. Risk of bias for included studies was assessed with SYRCLE tool. Heterogeneity among studies was evaluated according to Cochrane Handbook using Cochrane's Q test and I2 statistic. Results A total of 297 articles were retrieved, and after screening and evaluation, 19 animal studies were finally included for meta-analysis. These 19 studies covered four strains: SD rats, C57BL/6 mice, BALB/c mice, and Kunming mice. SYRCLE scores ranged from 3 to 4. Egger's test indicated potential publication bias (P<0.05), and Cochrane's Q test and I2 statistic indicated substantial heterogeneity among studies. Meta-analysis results of 19 animal studies showed that single-entity Astragali Radix preparation (Astragali Radix injection) could reduce serum amylase (AMS) levels, an AP-specific indicator. The Astragali Radix ingredients could decrease both AMS and lipase (LPS) levels. Astragali Radix injection or Astragali Radix ingredients could reduce serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), while increasing interleukin-10 (IL-10) levels; could increase serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) , and decrease malondialdehyde (MDA) levels. High-dose groups of Astragali Radix injection or Astragali Radix ingredients were more effective than low-dose groups in reducing AMS, TNF-α, and IL-6 levels and increasing SOD levels, but dosage effect on MDA levels was not demonstrated. Conclusion Evidence-based analysis of animal experiment results shows that in various animal models including SD rats, C57BL/6 mice, BALB/c mice, and Kunming mice, Astragali Radix injection or Astragali Radix ingredients can effectively reduce expression or secretion levels of AP-specific indicators (AMS and LPS). The mechanisms may be related to some inflammatory mediators, including reducing TNF-α, IL-6, and IL-1β levels and increasing IL-10 levels; may also intervene in oxidative/antioxidative equilibrium, such as increasing SOD and GSH-PX levels and reducing MDA levels. Except for MDA, dose–response relationships are shown for reducing AMS, TNF-α, and IL-6 levels and increasing SOD levels with Astragali Radix injection or ingredients. However, due to high heterogeneity, potential publication bias risk, and species differences between animal models and human diseases in existing studies, further high-quality clinical trials or animal experiments are still needed in the future.

Key words: Astragali Radix, Astragali Radix injection, Acute Pancreatitis, Animal experiment, Meta-analysis, Rat, Mouse

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