The cholestatic fibrosis induced by α-naphthylisothiocyanate in mice and the inflammation pathway

doi:10.12047/j.cjap.5903.2020.034

Abstract

Abstract: Objective: To explore the development of cholestatic fibrosis induced by α-naphthylisothiocyanate (ANIT) and the inflammation pathways. Methods: Fifteen 129/Sv mice weighing (23±2) g were randomly divided into 2 groups: control group (n=5) and experiment group (n=10). The control group was fed commercial chow diet and the experiment group was fed the same diet supplemented with 0. 05% ANIT. Five mice in the experiment group were sacrificed on day 14 and 28 respectively. The gallbladder, serum and liver samples were collected. Biochemical indicators of cholestasis were detected following the procedures in the kit. Liver injury was evaluated by histopathological. Hepatic fibrosis and inflammatory response were analyzed by Q-PCR and WB. Results: Compared with the control group, total bile acid (TBA), the main cholestasis biomarker, was increased from (3. 2±0. 9) μmol/L to (31. 6±4. 3) μmol/L in A-D14 group. AST and ALT, the biomarkers of liver injury, were also increased significantly (P＜0. 05). The expression levels of fibrotic factor tissue inhibitors of metalloproteinases 1 (TIMP-1), monocyte chemoattractant protein 1 (MCP-1) and collagen protein I (Collagen I) were higher than those of control group (P＜0. 05). The expressions of fibrosis protein Collagen I and α-SMA were also up-regulated. The collagen fibers of the liver were largely deposited and the liver fibrosis occurred (P＜0. 05). The expression of inflammatory factors was higher than the control group, JNK, c-Jun and STAT3 were activated (P＜0. 05). In A-D28 group, except AST, matrix metalloproteinases 2 (MMP-2) and Collagen I indicators were slightly decreased, other indicators of cholestasis, liver injury, liver fibrosis and inflammation continued to be up-regulated or stable (P＜0. 05). Conclusion: After 14-day treatment with 0. 05% ANIT diet, significant cholestatic liver fibrosis occurred in mice. After 28 days of treatment, cholestasis liver fibrosis kept stable. The JNK inflammatory pathway played a crucial role in the development of liver fibrosis.

Key words: ANIT, cholestatic, liver fibrosis, jnk pathway, mice

CLC Number:

R366

LUO Yi-shuang, ZHENG Xiu-ting, ZHANG Hao-yue, XU Li-ping, QIU Jia-peng, XU Gang-ming, LIU Ai-ming. The cholestatic fibrosis induced by α-naphthylisothiocyanate in mice and the inflammation pathway[J]. CJAP, 2020, 36(2): 152-156.

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