中药配伍减轻雷公藤制剂肝毒性的系统评价
|
摘要
目的:系统评价不同中药配伍减轻雷公藤制剂肝毒性的效果。方法:检索中文、英文数据库,纳入有关中药配伍减轻雷公藤制剂肝毒性的大鼠实验研究,提取干预前后血清生化指标丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的数据,采用Cochrane协作网的风险偏倚评估工具对纳入研究进行方法学质量评价,采用Stata 14.0软件进行Meta分析。结果:共纳入23篇实验研究文献。直接Meta分析结果显示,中药配伍可降低雷公藤制剂所致的大鼠血清ALT[SMD=-2.04,95%CI(-2.39,-1.69),P<0.01]和AST[SMD=-1.68,95%CI(-2.01,-1.36),P<0.01]水平升高。对单味中药配伍的研究进行间接网状Meta分析,结果表明单味中药配伍对雷公藤制剂所致大鼠肝毒性的减毒效应排序为:生地黄>白芍>甘草>三七>菟丝子>黄芪>青风藤>僵蚕。结论:中药配伍可减轻雷公藤制剂所致的大鼠肝毒性,且单味中药生地黄、白芍、甘草、三七、菟丝子配伍的减毒效果较为显著。
Objective: To systematically evaluate the effects of compatibility of different Chinese medicines on reducing hepatotoxicity of Tripterygium wilfordii preparations. Methods: Chinese and English databases were retrieved, and the experiment researches about compatibility of Chinese medicine on reducing hepatotoxicity of Tripterygium wilfordii preparations in rats were included. The data of serum biochemical indicators ALT and AST before and after intervention were extracted. The risk bias assessment tool of Cochrane collaboration network was used to evaluate the methodological quality of the included researches, and Stata 14.0 software was used to carry out Meta analysis. Results: Twenty-three experimental research literatures were included. The results of direct Meta analysis showed that the compatibility of Chinese medicine could reduce the serum levels of ALT [SMD=-2.04, 95%CI(-2.39,-1.69), P<0.01] and AST [SMD=-1.68, 95%CI(-2.01,-1.36), P<0.01] in rats with Tripterygium wilfordii preparations induced hepatotoxicity. For the compatibility of single Chinese medicine, the results of indirect network Meta analysis showed that, the order of effect of single Chinese medicine compatibility on reducing hepatotoxicity induced by Tripterygium wilfordii preparations in rats was as follows: Rehmanniae Radix > Paeoniae Radix Alba> Glycyrrhizae Radix et Rhizoma > Notoginseng Radix et Rhizoma > Cuscutae Semen > Astragali Radix > Sinomenii Caulis > Bombyx Batryticatus. Conclusion: Compatibility of Chinese medicine can alleviate the hepatotoxicity caused by Tripterygium wilfordii preparations in rats, and the compatibility of Rehmanniae Radix, Paeoniae Radix Alba, Glycyrrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and Cuscutae Semen shows significant effects on reducing hepatotoxicity.
Objective: To systematically evaluate the effects of compatibility of different Chinese medicines on reducing hepatotoxicity of Tripterygium wilfordii preparations. Methods: Chinese and English databases were retrieved, and the experiment researches about compatibility of Chinese medicine on reducing hepatotoxicity of Tripterygium wilfordii preparations in rats were included. The data of serum biochemical indicators ALT and AST before and after intervention were extracted. The risk bias assessment tool of Cochrane collaboration network was used to evaluate the methodological quality of the included researches, and Stata 14.0 software was used to carry out Meta analysis. Results: Twenty-three experimental research literatures were included. The results of direct Meta analysis showed that the compatibility of Chinese medicine could reduce the serum levels of ALT [SMD=-2.04, 95%CI(-2.39,-1.69), P<0.01] and AST [SMD=-1.68, 95%CI(-2.01,-1.36), P<0.01] in rats with Tripterygium wilfordii preparations induced hepatotoxicity. For the compatibility of single Chinese medicine, the results of indirect network Meta analysis showed that, the order of effect of single Chinese medicine compatibility on reducing hepatotoxicity induced by Tripterygium wilfordii preparations in rats was as follows: Rehmanniae Radix > Paeoniae Radix Alba> Glycyrrhizae Radix et Rhizoma > Notoginseng Radix et Rhizoma > Cuscutae Semen > Astragali Radix > Sinomenii Caulis > Bombyx Batryticatus. Conclusion: Compatibility of Chinese medicine can alleviate the hepatotoxicity caused by Tripterygium wilfordii preparations in rats, and the compatibility of Rehmanniae Radix, Paeoniae Radix Alba, Glycyrrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and Cuscutae Semen shows significant effects on reducing hepatotoxicity.
引文
[1] 国家中医药管理局《中华本草》编委会.中华本草[M].上海:上海科学技术出版社,1999:206.
[2] LAW S K,SIMMONS M P,TECHEN N,et al.Molecular analyses of the Chinese herb Leigongteng (Tripterygium wilfordii Hook.f.)[J].Phytochemistry,2011,72(1):21- 26.
[3] LI X J,JIANG Z Z,ZHANG L Y.Triptolide:progress on research in pharmacodynamics and toxicology[J].J Ethnopharmacol,2014,155(1):67- 79.
[4] WANG J,ZOU Z H,XIA H L,et al.Strengths and weaknesses of immunotherapy for advanced non- small- cell lung cancer:a meta- analysis of 12 randomized controlled trials[J].PLoS One,2012,7(3):e32695.
[5] 李波霖,周宾宾,金昕,等.督脉对比夹脊电针治疗对脊髓损伤大鼠下肢功能恢复作用的网状Meta分析[J].中国中医基础医学杂志,2016,22(12):1676- 1680.
[6] 张超,徐畅,曾宪涛.网状Meta分析中网状关系图的绘制[J].中国循证医学杂志,2013,13(11):1382- 1386.
[7] 张超,鄢金柱,孙凤,等.网状Meta分析一致性的鉴别与处理方法[J].中国循证医学杂志,2014,14(7):884- 888.
[8] CHAIMANI A,HIGGINS J P,MAVRIDIS D,et al.Graphical tools for network meta- analysis in STATA[J].PLoS One,2013,8(10):e76654.
[9] 董捷鸣,章从恩,于小红,等.HMGB1介导的炎症通路在雷公藤致大鼠肝损伤中的作用研究[J].中国药房,2018,29(5):633- 636.
[10] 李波.复方雷公藤汤对肾病大鼠减毒增效作用的实验研究[D].沈阳:辽宁中医药大学,2007.
[11] 朱胜楠,张靖,谭亲友,等.甘草水提物对雷公藤甲素致大鼠急性肝损伤的改善作用及对其体内IL- 10、TNF- α水平的影响[J].中国药房,2019,30(2):216- 220.
[12] 胡骞.甘草调节UGT1A1和MRP2对雷公藤甲素潜在肝损伤的保肝机制初探[D].桂林:桂林医学院,2017.
[13] 周文静,柴智,王永辉,等.归脾汤对雷公藤醇提物致急性肝损伤的保护作用[J].中国实验方剂学杂志,2012,18(9):169- 171.
[14] 陆艳,谢彤,张亚杰,等.基于“异类相制”理论的雷公藤复方配伍对CYP450酶系的影响[J].中华中医药杂志,2017,32(3):1050- 1056.
[15] 李桓.基于“异类相制”理论的雷公藤复方配伍减毒方法及代谢组学机制研究[D].南京:南京中医药大学,2015.
[16] 刘蒙竹.基于肠吸收动力学及代谢组学的清络通痹复方配伍对雷公藤减毒作用的初步探索[D].南京:南京中医药大学,2014.
[17] 柳璋璞.基于肝毒性的雷公藤复方配伍减毒研究[D].南京:南京中医药大学,2013.
[18] 刘乐.雷公藤不同时间给药对胶原诱导关节炎大鼠肝功能损伤的探讨[D].唐山:华北理工大学,2017.
[19] 秦思,李琼,于茜,等.雷公藤多苷配伍黄芪总皂苷对大鼠关节炎的减毒增效作用[J].数理医药学杂志,2016,29(4):540- 542.
[20] 乔欢,闫润红.雷公藤和雷公藤加逍遥散对CIA大鼠模型的抗炎作用及肝损伤情况的对比研究[J].世界中西医结合杂志,2017,12(3):357- 360.
[21] 李春庆,孙伟,邵家德,等.雷至胶囊对嘌呤霉素氨基核苷肾病的减毒增效作用[J].中国实验方剂学杂志,2011,17(22):172- 177.
[22] 吴汉利.雷至胶囊治疗阿霉素肾病大鼠肾损害的机理研究[D].南京:南京中医药大学,2010.
[23] 王蓝.水飞蓟素和富硒蛹虫草对雷公藤甲素致大鼠肝损伤的保护作用研究[D].广州:广州中医药大学,2017.
[24] 刘泽洲.菟丝子醇提物、雷公藤多苷配伍降低大鼠肝毒性的实验研究[D].北京:北京中医药大学,2015.
[25] 柴智,樊慧杰,王永辉,等.逍遥散对雷公藤致大鼠急性肝损伤的防治作用研究[J].世界中西医结合杂志,2014,9(1):27- 29.
[26] 柴智,樊慧杰,周文静,等.逍遥散对雷公藤致急性肝损伤大鼠肝脏组织Bcl- 2、Bax蛋白表达及Caspase- 3活性的影响[J].中医杂志,2018,59(15):1328- 1331.
[27] 成遥,张贺,孟楣,等.新风胶囊肝肾亚急性毒性实验研究[J].安徽医药,2015,19(8):1450- 1453.
[28] 卫艳玲.益肾饮对雷公藤多甙治疗系膜增殖性肾小球肾炎减毒增效的实验研究[D].济南:山东中医药大学,2007.
[29] 胡祖光,刘劲,刘惠纯,等.中药对抗雷公藤提取物毒性的研究Ⅱ.对雷公藤提取物致毒大鼠若干生化指标的影响[J].中药药理与临床,1994,10(4):37- 38.
[30] ZHANG Q H,LI Y Q,LIU M Z,et al.Compatibility with Panax notoginseng and Rehmannia glutinosa Alleviates the Hepatotoxicity and Nephrotoxicity of Tripterygium wilfordii via Modulating the Pharmacokinetics of Triptolide[J].Int J Mol Sci,2018,19(1):305.
[31] YANG G H,WANG L,YU X T,et al.Protective Effect of 18β- Glycyrrhetinic Acid against Triptolide- Induced Hepatotoxicity in Rats[J].Evid Based Complement Alternat Med,2017,2017:3470320.doi:10.1155/2017/3470320.
[32] WEI M J,ZHENG Z Y,SHI L,et al.Natural Polyphenol Chlorogenic Acid Protects Against Acetaminophen- Induced Hepatotoxicity by Activating ERK/Nrf2 Antioxidative Pathway[J].Toxicol Sci,2018,162(1):99- 112.
[33] XI C,PENG S J,WU Z P,et al.Toxicity of triptolide and the molecular mechanisms involved[J].Biomed Pharmacother,2017,90:531- 541.
[34] LI J,SHEN F H,GUAN C W,et al.Activation of Nrf2 protects against triptolide- induced hepatotoxicity[J].PLoS One,2014,9(7):e100685.
[35] CAO L J,YAN M,MA Y X,et al.Isoliquiritigenin protects against triptolide- induced hepatotoxicity in mice through Nrf2 activation[J].Pharmazie,2016,71(7):394- 397.
[36] ZHANG Y C,LI J,LEI X L,et al.Influence of Verapamil on Pharmacokinetics of Triptolide inRats[J].Eur J Drug Metab Pharmacokinet,2016,41(4):449- 456.
[37] TAI T,HUANG X,SU Y W,et al.Glycyrrhizin accelerates the metabolism of triptolide through induction of CYP3A in rats[J].J Ethnopharmacol,2014,152(2):358- 363.
[38] 程鉥泺,言枫,顾一煌.电针足三里对雷公藤甲素致急性肝损伤大鼠IL- 10与TNF- α的影响[J].中国中医基础医学杂志,2017,23(2):245- 246.
[39] 李冬艳.当归穴位埋植剂微创埋植对肾虚型卵巢早衰小鼠血清E2、P水平的影响[D].大连:大连医科大学,2010.
[40] 何欣,欧阳五庆,赵兴华,等.纳米乳对雷公藤多苷增效减毒作用研究[J].浙江大学学报(农业与生命科学版),2008,34(3):261- 265.
[2] LAW S K,SIMMONS M P,TECHEN N,et al.Molecular analyses of the Chinese herb Leigongteng (Tripterygium wilfordii Hook.f.)[J].Phytochemistry,2011,72(1):21- 26.
[3] LI X J,JIANG Z Z,ZHANG L Y.Triptolide:progress on research in pharmacodynamics and toxicology[J].J Ethnopharmacol,2014,155(1):67- 79.
[4] WANG J,ZOU Z H,XIA H L,et al.Strengths and weaknesses of immunotherapy for advanced non- small- cell lung cancer:a meta- analysis of 12 randomized controlled trials[J].PLoS One,2012,7(3):e32695.
[5] 李波霖,周宾宾,金昕,等.督脉对比夹脊电针治疗对脊髓损伤大鼠下肢功能恢复作用的网状Meta分析[J].中国中医基础医学杂志,2016,22(12):1676- 1680.
[6] 张超,徐畅,曾宪涛.网状Meta分析中网状关系图的绘制[J].中国循证医学杂志,2013,13(11):1382- 1386.
[7] 张超,鄢金柱,孙凤,等.网状Meta分析一致性的鉴别与处理方法[J].中国循证医学杂志,2014,14(7):884- 888.
[8] CHAIMANI A,HIGGINS J P,MAVRIDIS D,et al.Graphical tools for network meta- analysis in STATA[J].PLoS One,2013,8(10):e76654.
[9] 董捷鸣,章从恩,于小红,等.HMGB1介导的炎症通路在雷公藤致大鼠肝损伤中的作用研究[J].中国药房,2018,29(5):633- 636.
[10] 李波.复方雷公藤汤对肾病大鼠减毒增效作用的实验研究[D].沈阳:辽宁中医药大学,2007.
[11] 朱胜楠,张靖,谭亲友,等.甘草水提物对雷公藤甲素致大鼠急性肝损伤的改善作用及对其体内IL- 10、TNF- α水平的影响[J].中国药房,2019,30(2):216- 220.
[12] 胡骞.甘草调节UGT1A1和MRP2对雷公藤甲素潜在肝损伤的保肝机制初探[D].桂林:桂林医学院,2017.
[13] 周文静,柴智,王永辉,等.归脾汤对雷公藤醇提物致急性肝损伤的保护作用[J].中国实验方剂学杂志,2012,18(9):169- 171.
[14] 陆艳,谢彤,张亚杰,等.基于“异类相制”理论的雷公藤复方配伍对CYP450酶系的影响[J].中华中医药杂志,2017,32(3):1050- 1056.
[15] 李桓.基于“异类相制”理论的雷公藤复方配伍减毒方法及代谢组学机制研究[D].南京:南京中医药大学,2015.
[16] 刘蒙竹.基于肠吸收动力学及代谢组学的清络通痹复方配伍对雷公藤减毒作用的初步探索[D].南京:南京中医药大学,2014.
[17] 柳璋璞.基于肝毒性的雷公藤复方配伍减毒研究[D].南京:南京中医药大学,2013.
[18] 刘乐.雷公藤不同时间给药对胶原诱导关节炎大鼠肝功能损伤的探讨[D].唐山:华北理工大学,2017.
[19] 秦思,李琼,于茜,等.雷公藤多苷配伍黄芪总皂苷对大鼠关节炎的减毒增效作用[J].数理医药学杂志,2016,29(4):540- 542.
[20] 乔欢,闫润红.雷公藤和雷公藤加逍遥散对CIA大鼠模型的抗炎作用及肝损伤情况的对比研究[J].世界中西医结合杂志,2017,12(3):357- 360.
[21] 李春庆,孙伟,邵家德,等.雷至胶囊对嘌呤霉素氨基核苷肾病的减毒增效作用[J].中国实验方剂学杂志,2011,17(22):172- 177.
[22] 吴汉利.雷至胶囊治疗阿霉素肾病大鼠肾损害的机理研究[D].南京:南京中医药大学,2010.
[23] 王蓝.水飞蓟素和富硒蛹虫草对雷公藤甲素致大鼠肝损伤的保护作用研究[D].广州:广州中医药大学,2017.
[24] 刘泽洲.菟丝子醇提物、雷公藤多苷配伍降低大鼠肝毒性的实验研究[D].北京:北京中医药大学,2015.
[25] 柴智,樊慧杰,王永辉,等.逍遥散对雷公藤致大鼠急性肝损伤的防治作用研究[J].世界中西医结合杂志,2014,9(1):27- 29.
[26] 柴智,樊慧杰,周文静,等.逍遥散对雷公藤致急性肝损伤大鼠肝脏组织Bcl- 2、Bax蛋白表达及Caspase- 3活性的影响[J].中医杂志,2018,59(15):1328- 1331.
[27] 成遥,张贺,孟楣,等.新风胶囊肝肾亚急性毒性实验研究[J].安徽医药,2015,19(8):1450- 1453.
[28] 卫艳玲.益肾饮对雷公藤多甙治疗系膜增殖性肾小球肾炎减毒增效的实验研究[D].济南:山东中医药大学,2007.
[29] 胡祖光,刘劲,刘惠纯,等.中药对抗雷公藤提取物毒性的研究Ⅱ.对雷公藤提取物致毒大鼠若干生化指标的影响[J].中药药理与临床,1994,10(4):37- 38.
[30] ZHANG Q H,LI Y Q,LIU M Z,et al.Compatibility with Panax notoginseng and Rehmannia glutinosa Alleviates the Hepatotoxicity and Nephrotoxicity of Tripterygium wilfordii via Modulating the Pharmacokinetics of Triptolide[J].Int J Mol Sci,2018,19(1):305.
[31] YANG G H,WANG L,YU X T,et al.Protective Effect of 18β- Glycyrrhetinic Acid against Triptolide- Induced Hepatotoxicity in Rats[J].Evid Based Complement Alternat Med,2017,2017:3470320.doi:10.1155/2017/3470320.
[32] WEI M J,ZHENG Z Y,SHI L,et al.Natural Polyphenol Chlorogenic Acid Protects Against Acetaminophen- Induced Hepatotoxicity by Activating ERK/Nrf2 Antioxidative Pathway[J].Toxicol Sci,2018,162(1):99- 112.
[33] XI C,PENG S J,WU Z P,et al.Toxicity of triptolide and the molecular mechanisms involved[J].Biomed Pharmacother,2017,90:531- 541.
[34] LI J,SHEN F H,GUAN C W,et al.Activation of Nrf2 protects against triptolide- induced hepatotoxicity[J].PLoS One,2014,9(7):e100685.
[35] CAO L J,YAN M,MA Y X,et al.Isoliquiritigenin protects against triptolide- induced hepatotoxicity in mice through Nrf2 activation[J].Pharmazie,2016,71(7):394- 397.
[36] ZHANG Y C,LI J,LEI X L,et al.Influence of Verapamil on Pharmacokinetics of Triptolide inRats[J].Eur J Drug Metab Pharmacokinet,2016,41(4):449- 456.
[37] TAI T,HUANG X,SU Y W,et al.Glycyrrhizin accelerates the metabolism of triptolide through induction of CYP3A in rats[J].J Ethnopharmacol,2014,152(2):358- 363.
[38] 程鉥泺,言枫,顾一煌.电针足三里对雷公藤甲素致急性肝损伤大鼠IL- 10与TNF- α的影响[J].中国中医基础医学杂志,2017,23(2):245- 246.
[39] 李冬艳.当归穴位埋植剂微创埋植对肾虚型卵巢早衰小鼠血清E2、P水平的影响[D].大连:大连医科大学,2010.
[40] 何欣,欧阳五庆,赵兴华,等.纳米乳对雷公藤多苷增效减毒作用研究[J].浙江大学学报(农业与生命科学版),2008,34(3):261- 265.