Idiosyncratic hepatotoxicity evaluation of Zhuangguguanjie wan mediated by immune stress
10.16438/j.0513-4870.2017-0303
- VernacularTitle:免疫应激介导的壮骨关节丸致特异质肝损伤评价
- Author:
Jin-fa TANG
1
;
Xiao-yan WANG
2
;
Qiang WEN
3
;
Shu TANG
4
;
Feng SANG
2
;
Wei-xia LI
2
;
Yu-hui LI
5
;
Chun-yu LI
1
;
Cong-en ZHANG
1
;
Ming NIU
1
;
Zhao-fang BAI
1
;
Jia-bo WANG
1
;
Xiao-he XIAO
1
Author Information
1. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
2. The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China
3. Clinical Pharmacology Institute, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
4. The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
5. School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450008, China
- Publication Type:SPECIAL REPORTS
- Keywords:
Zhuangguguanjie wan;
idiosyncratic hepatotoxicity;
immunological stress;
cytokine;
T lymphocyte
- From:
Acta Pharmaceutica Sinica
2017;52(7):1033-1040
- CountryChina
- Language:Chinese
-
Abstract:
On basis of the idiosyncratic lipopolysaccharide(LPS)-mediated hepatotoxicity model, liver injury induced by Zhuangguguanjie wan(ZGW)was evaluated, and the mechanism was explored. Idiosyncratic hepatotoxicity model was established in rats by injecting LPS at a dosage of 2.8 mg·kg-1. Rats were randomly divided into the normal control group, LPS group, ZGW group and LPS+ZGW group. Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were analyzed in serum; pathological changes(HE staining)and the content of cytokines of liver were tested; and immune cell subpopulation ration were determined in blood and liver. Compared with the control group, the ZGW group and LPS group had no significant changes in ALT, AST and liver pathology(P> 0.05); while the ZGW+LPS group exhibited an elevation in ALT and AST(P< 0.05). Disorder of liver lobular arrangement and irregular island-like or massive necrosis of liver cells were observed in the group. Several cytokines in the liver were increased in LPS group and ZGW+LPS group(P< 0.05 or P< 0.01), and the level in ZGW+LPS group was higher than that of LPS group. Compared with the control group, the ratio of CD3+ T cell/lymphocyte of blood in LPS group was significantly decreased(P< 0.01); while the percentage of CD3+ T cells in the liver were significantly increased(P< 0.05). The contents of immune cells of blood had no significant changes between LPS group and ZGW+LPS group(P> 0.05). CD3+ T cell in the liver of ZGW+LPS group was significantly increased over the LPS group(P< 0.05). Aggregation or activity of CD3+ T cell was increased by ZGW combined with LPS. These results suggest that ZGW could promote T lymphocyte recruitment to liver under the immune activation state leading to inflammatory response, which may contribute to idiosyncratic liver injury.