楮实子对药物性肝损伤大鼠氧化应激因子的影响

doi:10.16333/j.1001-6880.2019.9.020

天然产物研究与开发 ›› 2019, Vol. 31 ›› Issue (9): 1617-1623.doi: 10.16333/j.1001-6880.2019.9.020

所属专题： No.2

楮实子对药物性肝损伤大鼠氧化应激因子的影响

王茜，张一昕*，石铖，郝蕾，韩雪，郭秋红，张晓栋

河北中医学院药学院，河北省高校中药组方制剂应用技术研发中心，石家庄 050200

出版日期:2019-10-09 发布日期:2019-10-23
基金资助:
国家自然基金青年基金(81503268）；河北省高等学校科学技术研究青年拔尖计划(BJ2016038）；中央财政公共卫生专项“2017年中药资源普查项目”(Z135080000022）

Effect of Broussonetiae Fructus on oxidative stress factors in rats with drug-induced liver injury

WANG Xi，ZHANG Yi-xin*，SHI Cheng，HAO Lei，HAN Xue，GUO Qiu-hong，ZHANG Xiao-dong

Hebei College of Traditional Chinese Medicine,Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation,Shijiazhuang 050200,China

Online:2019-10-09 Published:2019-10-23

摘要/Abstract

摘要： 为了探讨楮实子对对乙酰氨基酚（APAP）诱导的药物性肝损伤大鼠的保护作用以及对过氧化物酶体增殖物激活受体γ（PPAR-γ）、过氧化物酶体增殖物激活受体α（PPAR-α）、C-Ros癌基因1（ROS1）的调控作用。实验将50只SD大鼠随机分为正常组、模型组、水飞蓟宾组（44 mg/kg）和楮实子高、低剂量组（4.2、1.05 g生药/kg），每组10只。灌胃给予对乙酰氨基酚（1.2 kg/kg）制备肝损伤模型，给药组造模的同时给予相应药物治疗，连续30天。实验结束，收集血清、肝组织标本进行指标检测。结果显示，楮实子各剂量均能降低药物性肝损伤大鼠血清中谷丙转氨酶（ALT）和谷草转氨酶（AST）活性，降低总胆红素（TBIL）和直接胆红素（TBIL）的含量，升高血清中谷胱甘肽（GSH）含量、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性，降低丙二醛（MDA）含量以及ROS1的表达，上调PPAR-α mRNA的表达，下调PPAR-γ mRNA的表达。以上研究结果表明，楮实子能防治对乙酰氨基酚所致肝损伤，其作用机制可能是通过降低ROS1的表达、调节转录因子PPAR-α和PPAR-γ的基因表达，从而缓解氧化应激损伤来实现的。

关键词: 楮实子；药物性肝损伤；ROS1；PPAR-&alpha, ；PPAR-&gamma,

Abstract: To investigate the protective effect of Broussonetiae Fructus on acetaminophen-induced liver injury in rats and the regulatory effects on peroxisome proliferators activated receptor α (PPAR-α),peroxisome proliferators activated receptor γ (PPAR-γ),and C-Ros oncogene 1 (ROS1).50 SD rats were randomly divided into normal group,model group,silymarin group (44 mg/kg),Broussonetiae Fructus high and low dose groups (4.2，1.05 g crude drug/kg) with 10 rats in each group.The rat model of drug-induced liver injury was induced by acetaminophen (1.2 g/kg) orally once daily for 30 days.At the same time of modeling,normal group and model group were given saline infusions by gastric lavage,while the rest groups were given corresponding liquid infusions for 30 days.At the end of the experiment,the activities of AST,ALT,SOD,CAT and GSH-Px,and the contents of TBIL,DBIL,MDA and GSH in serum were measured.Part of the liver tissue was fixed with 4% paraformaldehyde solution,the pathological morphology of the liver was observed with HE staining,and the gene expression of PPAR-α and PPAR-γ were observed by RT-PCR,and the protein expression of ROS1 (C-Ros oncogene 1) was observed by immunohistochemistry.Our results showed that compared with the normal group,the levels of ALT,AST,TBIL and DBIL in rats of the model group were significantly increased,the content of MDA in serum and the gene expression of PPAR-γ in liver were increased,while the levels of SOD,GSH,GSH-Px and PPAR-α were decreased.Compared with the model group,different doses of Broussonetia Fructus could reduce the levels of ALT,AST,TBIL and DBIL,increase the levels of SOD,GSH,GSH-Px in serum,inhibit the gene expression of PPAR-γ and the protein expression of ROS1,and up-regulate the gene expression of PPAR-α.In conclusion,the results of this study suggest that Broussonetiae Fructus may have protective effect on the hepatic injury induced by acetaminophen in rats,and its mechanism may be related to the inhibition of oxidative stress and regulation the gene expression of PPAR-γ,PPAR-α,and the expression of ROS1 protein.

Key words: drug-induced liver injury, fructus broussonetia, ROS1, PPAR-&gamma, , PPAR-&alpha,

中图分类号:

R285.5

王茜，张一昕*，石铖，郝蕾，韩雪，郭秋红，张晓栋. 楮实子对药物性肝损伤大鼠氧化应激因子的影响[J]. 天然产物研究与开发, 2019, 31(9): 1617-1623.

WANG Xi，ZHANG Yi-xin*，SHI Cheng，HAO Lei，HAN Xue，GUO Qiu-hong，ZHANG Xiao-dong. Effect of Broussonetiae Fructus on oxidative stress factors in rats with drug-induced liver injury[J]. NATURAL PRODUCT RESEARCH AND DEVELOPMENT, 2019, 31(9): 1617-1623.

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楮实子对药物性肝损伤大鼠氧化应激因子的影响

Effect of Broussonetiae Fructus on oxidative stress factors in rats with drug-induced liver injury

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