“乌头-半夏”反药配伍对大鼠毒性研究的系统评价和Meta分析

doi:10.19803/j.1672-8629.20240438

摘要/Abstract

摘要： 目的系统评价“乌头-半夏”反药配伍对大鼠的毒性。方法检索中国知网、万方数据、维普网、中国生物医学文献服务系统、PubMed、Embase和Web of Science数据库,纳入国内外已发表的关于反药“乌头-半夏”对大鼠毒性的研究,检索时限均从建库至2024年4月3日。由2名研究者独立筛选文献、提取资料并运用SYRCLE动物实验偏倚风险评估工具进行文献质量评价,采用RevMan 5.4软件进行Meta分析。结果最终纳入13篇文献。Meta分析结果显示,与空白对照组相比,乌头-半夏（1∶1）配伍对正常大鼠的肝脏指数、谷丙转氨酶（ALT）、肌酐（Cr）和尿素氮（BUN）无显著影响,但可显著升高正常大鼠的心脏指数、肾脏指数、谷草转氨酶（AST）、碱性磷酸酶（ALP）、肌酸激酶（CK）和肌酸激酶同工酶（CK-MB）含量;与乌头单用组相比,乌头-半夏（1∶1）配伍可降低正常大鼠的AST、ALP、CK含量和肾脏指数,但不能降低心脏指数和CK-MB含量。附子-半夏（1∶1）配伍与空白对照组相比,仅CK含量显著升高,但与缺血再灌注损伤模型大鼠相比,附子-半夏可逆转模型大鼠CK水平的变化。定性分析结果显示,乌头/附子-半夏配伍对正常大鼠心、肝、肾的组织病理无影响或有轻度损伤,附子-半夏配伍可改善心脏病理模型大鼠的心脏病理损伤。结论现有动物实验表明,乌头-半夏（1∶1）配伍对正常大鼠的肝脏、心脏、肾脏指标均有一定影响,但可减轻乌头单用对正常大鼠的肝、肾损伤,对乌头引起的心脏损伤影响较小。附子-半夏（1∶1）配伍对正常大鼠肝、肾指标无明显影响,对心脏指标有一定影响,但对心脏病理模型大鼠有一定的保护作用。因此,乌头-半夏反药临床应用仍需持有谨慎态度;附子-半夏在辩证准确、方药合理的前提下,或可取得良效。

关键词: 乌头, 半夏, 十八反, 大鼠, 毒性, Meta分析

Abstract: Objective To systematically assess the toxicity of “aconitum carmichaelii-pinellia ternate” incompatible combination in rats. Methods CNKI, Wanang database, VIP, SinoMed, PubMed, Embase and Web of Science database were searched for related literature on toxicity of “aconitum carmichaelii-pinellia ternate” incompatible combination in rats that was published from inception to April 3, 2024. Two reviewers independently screened the literature, retrieved the data, and used the SYRCLE animal experiment bias risk assessment tool to evaluate risk bias before turning to RevMan 5.4 software for meta-analysis. Results A total of 13 experiments were included in this study. The results of meta-analysis showed that compared with the blank control group, the compatibility between aconitum carmichaelii and pinellia ternata at the 1∶1 ratio made no much difference to the liver index or contents of ALT, Cr and BUN of normal rats. However, the cardiac index, kidney index, and contents of AST, ALP, CK and CK-MB were increased significantly. Compared with the aconitum carmichaelii used alone group, aconitum carmichaelii and pinellia ternata at the 1∶1 ratio could reduce the contents of AST, ALP, CK and kidney indexes rather than the cardiac indexes and CK-MB content. Compared with the blank control group, the compatibility of aconiti lateralis radix praeparata and pinellia ternata at the 1∶1 ratio led to a significant increase of the CK content alone, but could reverse the change of CK levels in model rats compared with ischemia-reperfusion injury model rats. The results of qualitative analysis showed that the aconitum carmichaelii and pinellia ternata compatibility had no effect on or caused only mild injury to the histopathology of the heart, liver and kidney of normal rats. However, the aconiti lateralis radix praeparata and pinellia ternata compatibility could mitigate the cardiac pathological injury in rats in the cardiac pathological model. Conclusion The compatibility between aconitum carmichaelii and pinellia ternata at the 1∶1 ratio has some effect on liver, heart and kidney parameters in normal rats by alleviating the hepatic and renal injuries induced by aconitum carmichaelii alone, but exerts minimal effect on the cardiac damage caused by aconitum carmichaelii. Such compatibility has a protective effect on cardiac pathological model rats. Therefore, the incompatible combination of aconitum carmichaelii and pinellia ternata has to be used with caution. Aconiti lateralis radix praeparata and pinellia ternate may achieve good effects once accurate diagnosis and proper prescriptions are ensured.

Key words: Aconitum Carmichaelii, Pinellia Ternata, Eighteen Antagonisms, Rats, Toxicity, Meta-Analysis

中图分类号:

R994.11

王萍, 曹卉娟, 李梦琪, 张国治, 刘建平, 金雪晶. “乌头-半夏”反药配伍对大鼠毒性研究的系统评价和Meta分析[J]. 中国药物警戒, 2025, 22(2): 177-182.

WANG Ping, CAO Huijuan, LI Mengqi, ZHANG Guozhi, LIU Jianping, JIN Xuejing. Toxicity of “Aconitum Carmichaelii-Pinellia Ternata” Incompatible Combination: a Systematic Review and Meta-Analysis of Experimental Studies on Rats[J]. Chinese Journal of Pharmacovigilance, 2025, 22(2): 177-182.

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