姜黄素通过活化SIRT1拮抗CCl4诱导的小鼠肝脏纤维化

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摘要目的探讨沉默信息调节因子1（SIRT1）在四氯化碳（CCl4）致小鼠肝纤维化肝脏中的活性变化及姜黄素对肝纤维化的干预作用与分子机制。方法选取C57BL/6小鼠24只，随机分为正常组、模型组和姜黄素治疗组，每组8只。腹腔注射CCl4制备肝纤维化模型，建模后姜黄素治疗组给予0.5%羧甲基纤维素钠姜黄素悬液灌胃；模型组及正常组给予0.5%羧甲基纤维素钠灌胃，6周后处死小鼠。HE染色检测小鼠肝脏病理变化情况；检测各组血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、SIRT1活性；转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原（CollⅠ）mRNA表达，及Cleaved-caspase3、CollⅠ蛋白表达情况。结果模型组血清中ALT、AST、IL-6、TNF-α的表达量均显著高于正常组（均P ＜ 0.01），而治疗组血清ALT、AST、IL-6、TNF-α表达量均低于模型组，差异均有高度统计学意义（均P ＜ 0.01）；模型组肝脏组织细胞中SIRT1的酶活性低于正常组，差异有高度统计学意义（P ＜ 0.01）。治疗组SIRT1的酶活性明显高于模型组，差异有高度统计学意义（P ＜ 0.01）。模型组肝脏组织中TGF-β1、α-SMA的mRNA表达及CollⅠ表达量显著高于正常组，Cleaved-caspase3显著低于正常组，差异均有高度统计学意义（均P ＜ 0.01），治疗组TGF-β1、α-SMA的mRNA表达及CollⅠ表达量低于模型组，Cleaved-caspase3显著高于模型组，差异均有高度统计学意义（均P ＜ 0.01）。结论姜黄素对CCl4诱导的肝纤维化具有抑制作用，其机制可能是通过上调SIRT1活性，减轻炎性反应，抑制肝星状细胞的活化，拮抗肝脏纤维化。

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	申昌军1 张帅1 李浩鹏2 侯辰3 陈杰4

关键词 ：肝脏, 纤维化, 姜黄素, 炎性反应, 沉默信息调节因子1

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.

Key words： Liver Fibrosis Curcumin Inflammation Silencing information regulator 1

基金资助:陕西省重点研发计划项目（S2018-YF-YBSF-0676）；
陕西省科学技术研究发展计划项目（2016SF-024）。

作者简介: 申昌军（1983-），男，硕士；研究方向：肝脏纤维化。

引用本文:

申昌军1 张帅1 李浩鹏2 侯辰3 陈杰4. 姜黄素通过活化SIRT1拮抗CCl4诱导的小鼠肝脏纤维化[J]. 中国医药导报, 2020, 17(9): 11-15.
SHEN Changjun1 ZHANG Shuai1 LI Haopeng2 HOU Chen3 CHEN Jie4. Curcumin antagonized CCl4-induced liver fibrosis in mice by activating SIRT1. 中国医药导报, 2020, 17(9): 11-15.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2020/V17/I9/11

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