Cytokine analysis of Zhuangguguanjie wan-induced idiosyncratic liver injury based on mathematical modeling
10.16438/j.0513-4870.2018-0008
- VernacularTitle: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
- Author:
Jin-fa TANG
1
;
Xiao-yan WANG
1
;
Wei YANG
2
;
Wei-xia LI
1
;
Yu-hui LI
3
;
Zhao-fang BAI
4
;
Jia-bo WANG
4
;
Xiao-he XIAO
4
Author Information
1. The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China
2. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
3. Henan University of Chinese Medicine, Zhengzhou 450008, China
4. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
Zhuangguguanjie wan;
idiosyncratic hepatotoxicity;
cytokine;
Logistic regression;
Random forest method;
LASSO regression
- From:
Acta Pharmaceutica Sinica
2018;53(4):574-584
- CountryChina
- Language:Chinese
-
Abstract:
In this study, we used a mathematic-based modeling system to screen the cytokines that are sensitive to Zhuangguguanjie wan (ZGW)-induced idiosyncratic liver injury. The values of 27 cytokines were used as the data source in rat liver of lipopolysaccharide (LPS) + ZGW group. The alanine aminotransferase (ALT) activity value of liver function indexes was used as the outcome evaluation index of liver injury. Cytokines of ZGW-induced idiosyncratic liver injury were screened using Logistic regression, random forest method, LASSO Logistics regression and method of combining rule discovery algorithm with LASSO, and cytokines filtered out were revalued in THP1 macrophage. Susceptible cytokine combinations:interleukin-1β (IL-1β), epidermal growth factor (EGF) and interleukin-18 (IL-18) closely related to ZGW-induced idiosyncratic liver injury were obtained after preliminary screening analysis. The result of revalued in THP1 showed that the ethanolic extract of ZGW (EtZ) combined with IL-1β or IL-18 synergistically enhanced tumor necrosis factor-α (TNF-α) secretion in THP1 macrophage, and EtZ combined with IL-1β significantly enhanced interleukin-6 (IL-6) secretion in THP1 macrophage, but EtZ combined with EGF markedly inhibited IL-6 secretion in THP1 macrophage. The results suggest that the sensitive cytokines that can be characterized in the ZGW-induced idiosyncratic liver injury are IL-1β and IL-18, which provides a basis for screening the ZGW-induced idiosyncratic liver injury patients, and a new experimental evidence for clinical safety medication and risk prevention of ZGW.
