Comparative Study on Hepatotoxicity of Psoraleae Fructus in Rats and Mice

Zhao-juan GUO; Jing-xuan ZHANG; Qian-jun KANG; Jin-ying WU; Lin ZHANG; Ting WANG

doi:10.13422/j.cnki.syfjx.20201970

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Comparative Study on Hepatotoxicity of Psoraleae Fructus in Rats and Mice

Pharmacology | 更新时间：2020-12-10

- Comparative Study on Hepatotoxicity of Psoraleae Fructus in Rats and Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 22, Pages: 16-25(2020)
- 作者机构：
  
  北京中医药大学北京中医药研究院，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201970
  CLC： R22;R242;R2-031;R285.5
- Received：13 February 2020，
  
  Published Online：23 July 2020，
  
  Published：20 November 2020
- 稿件说明：
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郭兆娟,张晶璇,康倩君等.补骨脂对大鼠、小鼠肝毒性的比较[J].中国实验方剂学杂志,2020,26(22):16-25.

GUO Zhao-juan,ZHANG Jing-xuan,KANG Qian-jun,et al.Comparative Study on Hepatotoxicity of Psoraleae Fructus in Rats and Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(22):16-25.
郭兆娟,张晶璇,康倩君等.补骨脂对大鼠、小鼠肝毒性的比较[J].中国实验方剂学杂志,2020,26(22):16-25. DOI： 10.13422/j.cnki.syfjx.20201970.

GUO Zhao-juan,ZHANG Jing-xuan,KANG Qian-jun,et al.Comparative Study on Hepatotoxicity of Psoraleae Fructus in Rats and Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(22):16-25. DOI： 10.13422/j.cnki.syfjx.20201970.

摘要

目的

运用均匀设计法安排大鼠、小鼠长期毒性实验，探究补骨脂不同提取物对大鼠、小鼠肝毒性的影响，寻找引起补骨脂肝毒性的药物因素。

方法

以炮制、工艺、剂量、疗程为考察因素，采用均匀设计法安排各实验分组，220只SD大鼠与220只昆明小鼠，雌雄各半，分别分为正常组与实验1~8给药组，每日灌胃相应补骨脂（盐补骨脂50%醇提物大鼠2.57 g·kg

-1

，小鼠5.14 g·kg

-1

；生补骨脂95%醇提物大鼠0.51 g·kg

-1

，小鼠1.02 g·kg

-1

；盐补骨脂70%醇提物大鼠1.71 g·kg

-1

，小鼠3.42 g·kg

-1

；生补骨脂水提物大鼠1.03 g·kg

-1

，小鼠2.06 g·kg

-1

；盐补骨脂水提物大鼠1.03 g·kg

-1

，小鼠2.06 g·kg

-1

；生补骨脂70%醇提物大鼠1.71 g·kg

-1

，小鼠3.42 g·kg

-1

；盐补骨脂95%醇提物大鼠0.51 g·kg

-1

，小鼠1.02 g·kg

-1

；生补骨脂50%醇提物大鼠2.57 g·kg

-1

，小鼠5.14 g·kg

-1

），每周测定大鼠、小鼠体质量及摄食量1次。各疗程给药结束后，大鼠经戊巴比妥钠麻醉后，腹主动脉取血处死，小鼠采用摘眼球取血处死，取大鼠、小鼠肝脏及脑，计算脏器系数，取其血清测定肝功能相关指标，取其肝脏做苏木素-伊红（HE）染色后进行病理组织学检查。

结果

与正常组比较，实验3组雌性大鼠肝组织脏脑比明显升高（

0.05），雄性小鼠实验1~3组的肝脏质量、脏体比、脏脑比明显升高（

0.05，

0.01）；小鼠组织病理学表现较大鼠明显，主要表现为肝小叶中央区肝细胞肥大，以实验3组最为明显；根据多元回归方程分析，工艺与炮制、剂量、疗程均存在交互作用，工艺与肝毒性病理评分呈正相关，综合直观分析以及其他指标结果，工艺因素与补骨脂肝毒性最相关。

结论

补骨脂具有肝毒性，其肝毒性与乙醇提取工艺有关，醇提工艺肝毒性大于水提工艺肝毒性，70%醇提肝毒性最大，且存在种属差异，小鼠肝毒性表现较大鼠明显。

Abstract

Objective

Arrange long-term toxicity experiments by a uniform design method， so as to explore the effect of different extracts of Psoraleae Fructus on liver toxicity in rats and mice， and find the drug factors that cause psoralen liver toxicity.

Method

Based on the factors of processing， extraction technology， dosage and treatment course， each experimental group was arranged by uniform design method. A total of 220 SD rats and 220 Kunming mice with half male and half female were divided into normal groups and drug groups 1 to 8. The corresponding drugs （50% alcohol extract of salt Psoraleae Fructus in rats 2.57 g·kg

-1

， mice 5.14 g·kg

-1

， 95% alcohol extract of Psoraleae Fructus in rats 0.51 g·kg

-1

， mice 1.02 g·kg

-1

， 70% alcohol extract of salt Psoraleae Fructus in rats 1.71 g·kg

-1

， mice 3.42 g·kg

-1

， water extract of Psoraleae Fructus in rats 1.03 g·kg

-1

， mice 2.06 g·kg

-1

， water extract of salt

Psoraleae Fructus in rats 1.03 g·kg

-1

， mice 2.06 g·kg

-1

， 70% alcohol extract of Psoraleae Fructus in rats 1.71 g·kg

-1

， mice 3.42 g·kg

-1

， 95% alcohol extract of salt

Psoraleae Fructus in rats 0.51 g·kg

-1

， mice 1.02 g·kg

-1

， 50% alcohol extract of Psoraleae Fructus in rats 2.57 g·kg

-1

， mice 5.14 g·kg

-1

） were administered by gavage daily. The body weight and food intake of the rats and mice were measured once a week. After the treatment course， the rats were anesthetized with sodium pentobarbital， and blood was taken from the abdominal aorta， and the mice were sacrificed by removing the eyeballs， and the liver and brain were taken to calculate the organ coefficients. Serum was taken to determine liver function-related indicators， and the liver was taken for histopathological examination by hematoxylin-eosin （HE） staining.

Result

The liver visceral-brain ratio of female rats in group 3 were significantly increased （

0.05）. The liver quality， visceral-body ratio and visceral-brain ratio of male mice in groups 1 to 3 were significantly increased （

0.05，

0.01）. Histopathological manifestations in mice were more obvious than those in rats. Histopathology showed hepatocyte hypertrophy in the central area of liver lobules in mice， in particular in group 3. According to the multiple regression equation， there were interactions between extraction technology， processing， dosage and treatment course， and the extraction technology was positively correlated with the pathological score of liver injury. Based on the results of visual analysis and other indicators， it is concluded that the extraction technology factor is most relevant to psoralen liver toxicity of Psoraleae Fructus.

Conclusion

Psoraleae Fructus has the hepatotoxicity， which is related to ethanol extraction technology； alcohol extraction is more toxic than water extraction， and 70% ethanol extraction is the most toxic. Besides， there are species differences， with a more significant hepatotoxicity in mice than that in rats.

关键词

Keywords

references

国家药典委员会 . 中华人民共和国药典：一部［M］. 北京：中国医药科技出版社， 2015 ： 187 - 188 .

DEBORAH A S ， STEWART M . A rare case of acute hepatitis induced byuse of Babchi seeds as an ayurvedic remedy for vitiligo ［J］. BMJ Case Rep ， 2014 ， pii： bcr2013200958 .

NAM S W ， BAEK J T ， LEE D S ， et al . A case of acute cholestatic hepatitis associated with the seeds of psoraleacorylifolia （Boh-Gol-Zhee）［J］. Clin Toxicol （Phila）， 2005 ， 43 （ 6 ）： 589 - 591 .

李颖君，黄吟月 . 补骨脂致药物性肝损伤一例［J］. 上海医药， 2016 ， 37 （ 24 ）： 41 - 42 .

LI A ， GAO M ， ZHAO N ， et al . Acute liver failure associated with Fructus Psoraleae： a case report and literature review ［J］. BMC Complement Altern Med ， 2019 ， 19 （ 1 ）： 84 .

朱兰，逄瑜，杨乐，等 . 骨康胶囊肝损伤风险特点及因素分析［J］. 中国药物警戒， 2018 ， 15 （ 4 ）： 248 - 250，256 .

单小雯，梁锦锋，单伟光，等 . 骨康胶囊致不良反应93 例分析［J］. 中国药房， 2015 ， 26 （ 2 ）： 236 - 239 .

吴慧敏，姚志刚 . 骨康胶囊所致药物性肝损害二例［J］. 上海医药， 2018 ， 39 （ 24 ）： 33 - 34 .

周学士，尹翠兰，陆忠华，等 . 骨康胶囊引起严重肝损害2例及经验教训［J］. 实用肝脏病杂志， 2017 ， 20 （ 2 ）： 250 - 251 .

朱云，李永纲，王葽，等 . 595例中药导致肝损伤临床特征分析［J］. 中国中西医结合杂志， 2016 ， 36 （ 1 ）： 44 - 48 .

国家食品药品监督管理总局 . 药品不良反应信息通报（第16期）警惕壮骨关节丸引起的肝损害［EB/OL］. http：//www.sda.gov.cn/WS01/CL0078/32614.html http://www.sda.gov.cn/WS01/CL0078/32614.html ， 2008-8-9 / 2020-02-10 .

朱兰 , 逄瑜 , 杨乐 , 等 . 骨康胶囊肝损伤风险特点及因素分析 [J]. 中国药物警戒 , 2018 , 15 ( 4 ): 248 - 250，256 .

杨莉，王昭昕，卢国彦，等 . 补骨脂不同提取部位大鼠给药3个月的毒性比较研究［J］. 药物评价研究， 2019 ， 42 （ 8 ）： 1531 - 1536 .

杨莉，王昭昕，卢国彦，等 . 补骨脂水提药渣大鼠三个月长期毒性试验研究［J］. 药物评价研究， 2019 ， 42 （ 6 ）： 1128 - 1134 .

YU Y ， WANG P ， YU R ， et al . Long-term exposure of psoralen and isopsoralen induced hepatotoxicity and serum metabolites profiles changes in female rats ［J］. Metabolites ， 2019 ， 9 （ 11 ）： E263 .

WANG Y ， ZHANG H ， JIANG J M ， et al . Hepatotoxicity induced by psoralen and isopsoralen from Fructus Psoraleae： Wistar rats are more vulnerable than ICR mice ［J］. Food Chem Toxicol ， 2019 ， 3 （ 125 ）： 133 - 140 .

GAO Y ， WANG Z ， TANG J ， et al . New incompatible pair of TCM： Epimedii Folium combined with Psoraleae Fructus induces idiosyncratic hepatotoxicity under immunological stress conditions ［J］. Front Med ， 2020 ， 14 （ 3 ）： 68 - 80 .

方开泰 . 均匀设计与均匀设计表［M］. 北京：科学出版社， 1994 ： 13 .

李品，王琦，彭莉，等 . 痔血胶囊水提物和醇提物对大鼠肝毒性的影响［J］. 中国实验方剂学杂志， 2017 ， 23 （ 8 ）： 154 - 159 .

吴疆，魏巍，袁永兵 . 补骨脂的化学成分和药理作用研究进展［J］. 药物评价研究， 2011 ， 34 （ 3 ）： 217 - 219 .

李笑甜，宋忠臣 . 补骨脂及其活性成分免疫调节作用研究进展［J］. 现代免疫学， 2017 ， 37 （ 1 ）： 80 - 83 .

李卓清，陈志永，徐小昆，等 . 补骨脂中活性成分的药代动力学研究进展［J］. 上海中医药大学学报， 2016 ， 30 （ 1 ）： 87 - 90 .

王停，董润生 . 一起中药临床试验严重不良事件带给我们的思考［J］. 中国新药杂志， 2008 ， 17 （ 14 ）： 1185 - 1187 .

MITCHELL J R ， JOLLOW D J ， POTTER W Z ， et al . Acetaminophen-inducedhepatic necrosis. I. Role of drug metabolism ［J］. J Pharmacol Exp Ther ， 1973 ， 187 （ 1 ）： 185 - 194 .

MCGILL R M ， WILLIAMS D C ， XIE Y C ， et al . Acetaminophen-induced liver injury in rats and mice： comparison of protein adducts， mitochondrial dysfunction， and oxidative stress in the mechanism of toxicity ［J］. Toxicol Appl Pharmacol ， 2012 ， 264 （ 3 ）： 387 - 394 .

JAESCHKE H ， RAMACHANDRAN A . Oxidant stress and lipid peroxidation in acetaminophen hepatotoxicity ［J］. React Oxyg Species ， 2018 ， 5 （ 15 ）： 145 - 158 .

YAN M ， HUO Y ， YIN S ， et al . Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions ［J］. Redox Biol ， 2018 ， 17 （ 2 ）： 274 - 283 .

王昭昕，翟玉霞，于英莉，等 . 补骨脂素对大小鼠肝CYP450酶4种亚型表达的影响［J］. 中国药理学与毒理学杂志， 2019 ， 33 （ 9 ）： 733 .

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