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-Analyses,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。使用SYRCLE工具对纳入文献进行偏倚风险评估;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I 2统计量进行评价;采用留一法进行敏感性分析,并使用Egger's test检验检测发表偏倚风险。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,以及C57BL/6小鼠、BALB/c小鼠和昆明小鼠3个品种的小鼠,SYRCLE评分为3∼4分;敏感性分析结果显示未发现有能显著影响异质性指标的研究;Egger's test检验结果为P<0.05,显示研究间存在一定的发表偏倚;Cochrane's Q检验和I 2统计量显示研究间异质性较大。19项动物实验相关文献的Meta分析结果显示,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,AMY)的水平;黄芪成分可使AMY与脂肪酶(lipase,LPS)的水平降低。黄芪注射液或黄芪成分可使血清中肿瘤坏死因子(tumor necrosis factor,TNF)-α、白细胞介素(interleukin,IL)-6、IL-1β的水平降低,使IL-10的水平升高;并使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)的水平升高,使丙二醛(malondialdehyde,MDA)的水平降低。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AMY、TNF-α和IL-6的水平,同时升高SOD的水平,但未证明剂量对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(AMY、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AMY、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异质性较高、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。
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 China National Knowledge Infrastructure(CNKI),VIP Database for Chinese Technical Periodicals(VIP),Wanfang Data Knowledge Service Platform,China Biomedical Literature Database(CBMdisc),PubMed,and Web of Science(WOS)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 I²statistic.Sensitivity analysis was performed using the leave-one-out method,and publication bias risk was detected using Egger's test.Results A total of 297 articles were retrieved,and after screening and evaluation,19 animal studies were finally included for meta-analysis.These 19 publications cover SD rats,as well as three breeds of mice:C57BL/6 mice,BALB/c mice,and Kunming mice.SYRCLE scores ranged from 3 to 4.The results of the sensitivity analysis showed that no study significantly affected the heterogeneity index.The results of Egger's test showed a significant publication bias with P<0.05.Cochrane's Q test and I²statistic 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(AMY)levels,an AP-specific indicator.The Astragali Radix ingredients could decrease both AMY and lipase(LPS)levels.Astragali Radix injection or its ingredients could reduce serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β,while increasing 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 AMY,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 its ingredients can effectively reduce expression or secretion levels of AP-specific indicators(AMY and LPS).The mechanisms may be related to some inflammatory mediators,including reducing TNF-α,IL-6,and IL-1βlevels and increasing IL-10 levels;They 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 AMY,TNF-α,and IL-6 levels and increasing SOD levels with Astragali Radix injection or its 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.
作者
曹星新
李艾亦
侯婧涵
李明学
李艳艳
靳玮华
杨凤梅
段素琴
和占龙
CAO Xingxin;LI Aiyi;HOU Jinghan;LI Mingxue;LI Yanyan;JIN Weihua;YANG Fengmei;DUAN Suqin;HE Zhanlong(Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming 650018,China;College of Life Sciences,Yunnan university,Kunming 650091,China)
出处
《实验动物与比较医学》
2025年第5期561-573,共13页
Laboratory Animal and Comparative Medicine
基金
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)。
关键词
黄芪
急性胰腺炎
动物实验
META分析
大鼠
小鼠
Astragali Radix
Acute Pancreatitis
Animal experiment
Meta-analysis
Rat
Mouse
