基于统计建模的壮骨关节丸诱发特异质肝损伤相关易感性细胞因子分析

被引：15

作者：

唐进法 ^{[1
,2
]}

王晓艳 ^{[1
,2
]}

杨伟 ^{[3
]}

李伟霞 ^{[1
,2
]}

李宇辉 ^{[2
]}

柏兆方 ^{[4
]}

王伽伯 ^{[4
]}

肖小河 ^{[4
]}

机构：

[1] 河南中医药大学第一附属医院

[2] 河南中医药大学

[3] 中国中医科学院中医临床基础医学研究所

[4] 解放军医院全军中医药研究所

来源：

药学学报 | 2018年 / 53卷 / 04期

关键词：

壮骨关节丸; 特异质肝损伤; 细胞因子; Logistic回归; 随机森林法; LASSO回归法;

D O I：

暂无

中图分类号：

R285.5 [中药实验药理];

学科分类号：

100806 [中药药理学];

摘要：

利用数据建模的方式筛选壮骨关节丸(Zhuangguguanjie wan,ZGW)特异质肝损伤相关易感细胞因子。以脂多糖(lipopolysaccharide,LPS)+ZGW大鼠肝脏组织中27种细胞因子水平作为数据源,以肝功能指标谷丙转氨酶(alanine aminotransferase,ALT)活力值高低作为肝损伤结局的评价指标,采用Logistic回归法、分类树及随机森林法、LASSO Logistics回归法、规则发现算法与LASSO相结合的变量筛选方法,筛查ZGW特异质肝损伤相关易感细胞因子,并在THP1细胞上进行再评价。结果表明,初步筛选分析得到ZGW特异质肝损伤密切相关的易感细胞因子组合为白介素-1β(interleukin-1β,IL-1β)、白介素-18(interleukin-18,IL-18)和表皮细胞生长因子(epidermal growth factor,EGF),ZGW醇提物(ethanolic extract of ZGW,Et Z)联合IL-1β或IL-18协同增强THP1细胞肿瘤坏死因子(tumor necrosis factor-α,TNF-α)分泌,Et Z联合IL-1β协同增强THP1细胞白介素-6(interleukin-6,IL-6)的分泌,但Et Z联合EGF协同抑制THP1细胞IL-6的分泌。上述结果表明,能表征ZGW特异质肝损伤相关易感性细胞因子为IL-1β和IL-18,为临床ZGW特异质肝损伤患者的筛查提供依据,为ZGW临床安全用药及风险防控提供了新的实验证据。

引用

页码：574 / 584

页数：11

共 16 条

[1]

The chemical, genetic and immunological basis of idiosyncratic drug-induced liver injury [J].

Tailor, A. ;

Faulkner, L. ;

Naisbitt, D. J. ;

Park, B. K. .

HUMAN & EXPERIMENTAL TOXICOLOGY, 2015, 34 (12) :1310-1317

[2]

Interleukin-18 enhances IL-18R/Nox1 binding; and mediates TRAF3IP2-dependent smooth muscle cell migration. Inhibition by simvastatin.[J].Anthony J. Valente;Tadashi Yoshida;Reza Izadpanah;Patrice Delafontaine;Ulrich Siebenlist;Bysani Chandrasekar.Cellular Signalling.2013, 6

[3]

The primary role of hepatic metabolism in idiosyncratic drug-induced liver injury [J].

Amacher, David E. .

EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2012, 8 (03) :335-347

[4]

Lack of interleukin-1α or interleukin-1β inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice [J].

Kamari, Yehuda ;

Shaish, Aviv ;

Vax, Einav ;

Shemesh, Shay ;

Kandel-Kfir, Michal ;

Arbel, Yaron ;

Olteanu, Sarita ;

Barshack, Iris ;

Dotan, Shahar ;

Voronov, Elana ;

Dinarello, Charles A. ;

Apte, Ron N. ;

Harats, Dror .

JOURNAL OF HEPATOLOGY, 2011, 55 (05) :1086-1094

[5]

Involvement of the Immune System in Idiosyncratic Drug Reactions [J].

Zhang, Xiachu ;

Liu, Feng ;

Chen, Xin ;

Zhu, Xu ;

Uetrecht, Jack .

DRUG METABOLISM AND PHARMACOKINETICS, 2011, 26 (01) :47-59

[6]

PREDICTIVE LEARNING VIA RULE ENSEMBLES [J].

Frieman, Jerome H. ;

Popescu, Bogdan E. .

ANNALS OF APPLIED STATISTICS, 2008, 2 (03) :916-954

[7]

IL‐18; but not IL‐12; is required for optimal cytokine production by influenza virus‐specific CD8<sup>+</sup> T cells.[J].Alice E. Denton;Peter C. Doherty;Stephen J. Turner;Nicole L. La Gruta.European Journal of Immunology.2007, 2

[8]

免疫应激介导的壮骨关节丸致特异质肝损伤评价 [J].