[Effect of ronggan mixture on immunoregulation and hepatocyte apoptosis-related factors in concanavalin A induced acute immunological liver injury mice].
OBJECTIVE
To explore the effect of Ronggan Mixture (RM) on immunoregulation and hepatocyte apoptosis-related factors in concanavalin A (Con A) induced acute immunological liver injury mice.


METHODS
Totally 60 hepatitis B virus (HBV) transgenic mice were randomly divided into 6 groups, i.e., the blank control group, the model group, the RM group, the Herba Artemisiae Scopariae (HAS) group, the Yinchenhao Decoction (YD) group, and the Bifendate group, 10 mice in each group. The acute immunological liver injury model was established by tail vein injection of ConA. Fourteen days before modeling, normal saline was administered to mice in the blank control group and the model group. RM, YD, HAS decoction, and Bifendate solution was respectively given to mice in the RM group, the YD group, the HAS group, and the Bifendate group. The medication was performed once daily. One h after the last gastrogavage, phosphate buffer solution (PBS) was injected to mice in the blank control group from the tail vein. Modeling was conducted by injecting Con A at 3 microg/g body weight from the tail vein. Mice were sacrificed 8 h after modeling. Blood or tissue samples were collected to detect lab indicators such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), tumor necrosis factor alpha (TNF-alpha), interferon gamma (INF-gamma), IL-4, IL-10, Fas, FasL, Bax, and bcl-2.


RESULTS
There was significant difference in all lab indicators between the normal group and the blank control group (P < 0.05, P < 0.01). Compared with the model group, ALT and AST levels were significantly lower in the RM group and the Bifendate group (P < 0.01); TBil significantly decreased in the RM group (P < 0.01). The expression level of TNF-alpha decreased in the RM group (P <0.05). The expression level of IFN-gamma decreased in the RM group and the YD group (P < 0.05). The expression level of IL-4 could be elevated in all medicated groups (P < 0.05). RM could elevate the expression level of IL-10 (P < 0.05). The expression level of Fas in the liver tissue decreased in the RM group and the YD group (P < 0.05). The expression level of FasL decreased and the expression of bcl-2 gene increased in the RM group (both P < 0.05). The expression level of Bax was down-regulated in the RM group and the YD group (P < 0.05). The ratio of bcl-2/Bax was up-regulated in the RM group (P < 0.05). Meanwhile, RM showed better effect in decreasing expressions of ALT and AST than HAS (P < 0.05). The effect of increasing IL-10 expression levels was better in the RM group than in the YD group (P < 0.01). The effect of decreasing expressions of Fas and FasL was better in the RM group than in the HAS group, the YD group, and the Bifendate group (P < 0.05). The effect of enhancing the expression of IL-10 in the liver tissue was better in the RM group than in the HAS group (P < 0. 05).


CONCLUSIONS
RM had protective effect on Con A induced acute immunological liver injury mice, which might be achieved by changing the immunological balance of Thl/Th2 factors (decreasing expressions of TNF-alpha and IFN-gamma, elevating expressions of IL-10 and IL-4) and regulating hepatocyte apoptosis-related factors (down-regulating gene expressions of Fas, FasL, and Bax; up-regulating bcl-2 gene expression, and up-regulating the bcl-2/Bax ratio).
Department of Hepatic Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China.
Yin-qiang
YQ
Zhang
Department of Gastroenterology, China Academy of Chinese Medical Sciences, Beijing (100091), China.
Xu-dong
XD
Tang
Experimental Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China.
Feng-yun
FY
Wang
Department of Pathology, China Academy of Chinese Medical Sciences, Beijing (100091), China.
Bin
B
Yang
Department of Hepatic Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China.
Yan-ling
YL
Liu
Department of Hepatic Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China.
Peng
P
Guo
Department of Gastroenterology, China Academy of Chinese Medical Sciences, Beijing (100091), China.
Ping
P
Wang
Department of Gastroenterology, China Academy of Chinese Medical Sciences, Beijing (100091), China.
Li-qun
LQ
Bian
Experimental Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China.
Ying-pan
YP
Zhao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000473:pathology; D003208:Concanavalin A / Q000009:adverse effects; D016207:Cytokines / Q000276:immunology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D016207:Cytokines; D004365:Drugs, Chinese Herbal; D003208:Concanavalin A