Curcumin antagonized CCl4-induced liver fibrosis in mice by activating SIRT1
SHEN Changjun1 ZHANG Shuai1 LI Haopeng2 HOU Chen3 CHEN Jie4
1.The Second Ward of General Surgery, Yan′an People′s Hospital, Shannxi Province, Yan′an 716000, China;
2.Department of Orthopedics, the Second Affiliated Hospital of Xi′an Jiaotong University, Shannxi Province, Xi′an 710032, China;
3.the Third Department of Neurology, the Third Affiliated Hospital of Xi′an Jiaotong University Shaanxi Provincial People′s Hospital, Shannxi Province, Xi′an 710032, China;
4.Department of Burns and Cutaneous Surgery, the Second Affiliated Hospital of Xi′an Medical College Xijing Hosptital, Air Force Medical University, Shannxi Province, Xi′an 710032, China
Abstract:Objctive To investigate the activity of silencing information regulator 1 (SIRT1) in the liver of carbon tetrachloride (CCl4) induced liver fibrosis in mice, and to investigate the effect of curcumin on liver fibrosis and its molecular mechanism. Methods Twenty-four C57BL/6 mice were randomly divided into normal group, model group and Curcumin treatment group, with 8 mice in each group. Hepatic fibrosis model was prepared by intraperitoneal injection of CCl4. After the modeling, the curcumin treatment group was given 0.5% Carboxymethyl Cellulose Sodium Curcumin Suspension by gavage. The model group and the normal group were given 0.5% Sodium Carboxymethyl Cellulose by gavage, the mice were killed after 6 weeks. HE staining was used to detect the pathological changes of mouse liver. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and activity of SIRT1 were detected. Transforming growth factor β1 (TGF -β1), α-smooth muscle actin (α-SMA), collagen typeⅠ (Coll Ⅰ) mRNA expression, and Cleaved - caspase3, Coll Ⅰ protein expression. Results The expression levels of ALT, AST, IL-6 and TNF-α in serum of the model group were all significant higher than those of the normal group (all P < 0.01). The expression levels of ALT, AST, IL-6 and TNF-α in the treatment group were all lower than those in the model group, and the differences were highly statistically significant (all P < 0.01). The enzyme activity of SIRT1 in the liver cells of the model group was lower than that of the normal group, and the difference was highly statistically significant (P < 0.01). The enzyme activity of SIRT1 in the treatment group was significantly higher than that in the model group, and the difference was highly statistically significant (P < 0.01). Model group in the liver tissue, TGF-β1, α-SMA mRNA and Coll Ⅰ expression of amount of expression were significantly higher than those of normal group, Cleaved-caspase3 was significantly lower than that of normal group, with highly statistically significant differences (all P < 0.01). The mRNA expression of TGF-β1, α-SMA and Coll Ⅰ expression quantity in the treatment group were lower than those in the model group, Cleaved-caspase3 was significantly higher than that of model group, with highly statistically significant differences (all P < 0.01). Conclusion Curcumin has an inhibitory effect on CCl4-induced liver fibrosis, and the mechanism may be to up-regulate the activity of SIRT1, thereby reducing the inflammatory response, inhibiting the activation of hepatic stellate cells, and antagonizing liver fibrosis.