|
| Resveratrol improves CCl4 induced liver fibrosis in mice by regulating liver circadian clock |
| Hits 406 Download times 476 Received:September 18, 2022 |
| View Full Text View/Add Comment Download reader |
| DOI
10.11656/j.issn.1672-1519.2022.12.18 |
| Key Words
resveratrol;hepatic fibrosis;carbon tetrachloride;circadian clock |
| Author Name | Affiliation | E-mail | | QUE Renye | Department of Gastroenterology, Shanghai traditional Chinese medicin-integrated Hospital Affiliated to Shanghai University of traditional Chinese medicine, Shanghai 200082, China | | | DAI Yancheng | Department of Gastroenterology, Shanghai traditional Chinese medicin-integrated Hospital Affiliated to Shanghai University of traditional Chinese medicine, Shanghai 200082, China | | | LI Yong | Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China | | | ZHOU Yi | Department of Gastroenterology, Shanghai traditional Chinese medicin-integrated Hospital Affiliated to Shanghai University of traditional Chinese medicine, Shanghai 200082, China | elian_zhou@163.com |
|
| Abstract
|
| [Objective] To observe the intervention effect of resveratrol (Res) on carbon tetrachloride (CCL4)-induced hepatic fibrosis (HF) in mice and its regulatory effect on liver circadian clock. [Methods] Male C57BL/6 mice were randomly divided into control group,model group and resveratrol group,10 mouse in each group. The model group and resveratrol group were made by intraperitoneal injection of 20% CCl4 oil solution at a volume fraction of 2.5mL/kg,twice a week for 4 weeks. The control group was given intraperitoneal injection of olive oil at the same dose and frequency. Resveratrol was diluted with normal saline and the final concentration was 30 mg/kg for intraperitoneal injection intervention,once a day for 4 weeks. The control group and model group were given the same amount of normal saline and intraperitoneal injection at the same frequency. After 4 weeks,the mice were killed and serum and liver tissue samples were collected. The liver fibrosis was observed by HE staining,Masson staining and Sirius red staining. The activities of serum alanine aminotransferase (ALT),aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured by automatic biochemical analyzer,and the liver was detected by immunohistochemistry α-Smooth muscle actin (α-SMA) and collagen I (COL-1) were used to evaluate the degree of liver fibrosis. The expressions of clock gene in liver,including clock,brain and muscle aromatic hydrocarbon receptor nuclear like protein 1 (BMAL1),period 1 (Per1),period 2 (Per2),cryptochrome 1 (Cry1) and cryptochrome 2 (Cry2) were detected by real-time PCR and Western blot. [Results] Compared with the control group,the indexes of liver function such as ALT,AST and LDH in the model group were significantly increased. HE staining of pathological sections showed that the fibrous tissue in the portal area of the model group was proliferated,and the bile duct between hepatic lobules was significantly proliferated. Some segments wrapped around the hepatic lobules made its structure disordered. Masson staining and Sirius red staining showed that the collagen deposition in the portal area of the model group was significantly increased,and immunohistochemistry showed that the positive areas of α-SMA and COL-1 increased significantly. The results of real-time PCR and Western blot showed that the mRNA and protein expressions of clock, Bmal1,Per1,Per2,Cry1 and Cry2 decreased significantly. Resveratrol intervention can significantly reverse the changes of the above indicators. [Conclusion] Resveratrol can significantly reduce CCl4 induced liver fibrosis in mice,and the mechanism may be related to the regulation of liver circadian clock genes. |
|
|
|
|
|
|
|
