Establishment and optimization of C57BL/6J mice liver fibrosis model induced by carbon tetrachloride
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1.Affiliated Hospital of Liaoning University of Traditional Chinese Medicine;2.Guang '3.'4.anmen Hospital, China Academy of Chinese Medical Sciences;5.Marine Police Corps Hospital of Chinese People'6.s Armed Police Force

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Public Health Research and Development Project, Shenyang Science and Technology Bureau(21-173-9-37)

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    Abstract:

    Objective To optimize C57BL/6J mouse liver fibrosis model induced by different doses of carbon tetrachloride through imaging, molecular biology and pathology methods.Methods Thirty-six healthy C57BL/6J male mice were randomly divided into control group, 2 weeks group, 3 weeks group, 4 weeks group, 6 weeks group and 8 weeks group (n=6) after adaptive feeding for 1 week. The control group was intraperitoneally injected with 0.2 mL olive oil injection three times a week, and the positive control groups were intraperitoneally injected with 0.2 mL 20% CCl4-olive oil solution three times a week. The changes in body weight of mice in each group were recorded. Liver stiffness was measured on days 15, 22, 29, 43 and 57, and blood samples were collected, the mice were measured cereal third transaminase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), layer mucins (LN), type Ⅲ before collagen (PC-Ⅲ) and collagen type Ⅳ (Ⅳ-C) content, The liver tissues were stained with HE, Masson and Sirius red.The Metavir scoring system was used to evaluate the degree of liver fibrosis.Results Compared with the control group, the mice in the positive control groups were listless and clustered together. In terms of body weight, the 4-week group, 6-week group and 8-week group were significantly lower than the control group, while the 2-week group was significantly higher than the control group. Liver elastography showed a progressive increase in stiffness with the increase of administration time. Biochemical results show that, compared with the control group, the other groups ALT, AST levels were significantly higher, with the increase of drug delivery time, the positive control group HA, LN, PC-Ⅲ and Ⅳ-C levels showed a trend of rise. The pathological results showed that the degree of liver fibrosis was progressively aggravated with the increase of administration time. At 4 weeks, the pathological diagnosis of liver fibrosis was consistent with that of liver fibrosis, there was a trend of pseudolobules formation at 6 weeks, and pseudolobules were formed at 8 weeks, suggesting early cirrhosis.Conclusions The liver fibrosis model of C57BL/6J mice can be successfully established by intraperitoneal injection of 20% CCl4-olive oil solution three times a week for 4 consecutive weeks, which has good stability and rapid modeling. It can be used as an optimized scheme for the establishment of liver fibrosis model.

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History
  • Received:December 05,2023
  • Revised:April 23,2024
  • Adopted:May 08,2024
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