To explore the potential hepatocarcinogenic effect of aristolochic acid I (AAI) on 2-week-old C3H/HeN suckling mice and its possible mechanism.
Two-week-old C3H/HeN suckling mice were randomly divided into 3 groups, i.e., the vehicle control group (0.5% CMC-Na), the liver cancer positive agent model group (DEN 20 mg·kg-1) and the AAI group (AAI 10 mg·kg-1). After 9 months of observation after a single administration, the organs were taken for gross pathological and histopathological examination, and the levels of serum biochemical indicators such as ALT, AST and AFP in mice were detected. At the same time, the contents of IL-1β and IL-6, the expression of Ki67, CK19, NF-κB P65, Ras, Raf, and caspase-3 in mouse liver were detected.
In this experiment, AAI caused liver cancer in C3H/HeN suckling mice. The incidence of liver cancer in male and female mice were 78.57% and 41.67%, respectively. Compared with the vehicle control group, the levels of ALT, AST, AFP, IL-1β and IL-6 in the AAI group were significantly increased, and the expression of Ki67 and CK19 in liver were positive. The results of Western blot showed that AAI significantly increased the expression of NF-κB P65, P-AKT, Ras, C-Jun, C-Fos, C-MYC and Bcl-2, and significantly decreased the expression of IKBα, Bax and Caspase-3.
In this experiment, AAI caused liver cancer in 2-week-old C3H/HeN suckling mice. The mechanism may be related to the activation of PI3K/AKT inflammatory pathway in hepatocytes, Ras/AP1/C-MYC proliferation pathway and the inhibition of Bax/Bcl-2/Caspase-3 Mitochondrial apoptosis pathway.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |