基于IL-6/JAK2/STAT3信号通路研究岩白菜素对急性肝损伤大鼠的保护作用

doi:10.16333/j.1001-6880.2021.9.001

摘要/Abstract

摘要：

基于IL-6/JAK2/STAT3信号通路探讨岩白菜素对四氯化碳（CCl₄）致大鼠急性肝损伤的保肝作用及其作用机制。60只SD大鼠随机分为正常组、模型组、水飞蓟素（120 mg/kg）组、岩白菜素低、中、高（20、40、80 mg/kg）剂量组，每组10只。水飞蓟素组、岩白菜素各剂量组大鼠按照10 mL/kg灌胃给药，正常组和模型组灌胃相应体积溶剂，每日1次，连续1周。末次给药2 h后，除正常组以外，其余各组腹腔注射25%四氯化碳（CCl₄）橄榄油溶液2 mL/kg，建立急性肝损伤大鼠模型。禁食不禁水，16 h后眼球取血，并收集肝脏。生化法测定血清中谷丙转氨酶（ALT）、谷草转氨酶（AST）、白蛋白（ALB)、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）以及超氧化物歧化酶（SOD）的水平或活性。酶联免疫吸附法（ELISA）测定检测肝组织中白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）和白细胞介素-1β（IL-1β）的含量。采用HE染色观察肝组织的病理变化程度，免疫组化（IHC）观察肝组织中IL-6的表达水平，蛋白免疫印迹法（Western blot）检测IL-6/JAK2/STAT3通路相关蛋白的表达水平。实验结果表明，与模型组相比，岩白菜素各剂量组和水飞蓟素组大鼠肝组织炎症坏死和IL-6表达不同程度的减轻。岩白菜素可显著降低血清中的ALT、AST、MDA和肝组织中TNF-α、IL-6和IL-1β活性或水平，上调血清中ALB、SOD和GSH-Px的活性或水平，并且抑制IL-6/JAK2/STAT3通路相关蛋白的表达。综上所述，岩白菜素对CCl₄致急性肝损伤大鼠具有保护作用，其保肝机制可能与IL-6/JAK2/STAT信号通路介导的炎症反应和抗氧化有关。

关键词: 岩白菜素, 急性肝损伤, 四氯化碳, 炎症反应, IL-6/JAK2/STAT3信号通路

Abstract:

To explore the hepatoprotective effect and mechanism of bergenin on acute liver injury induced by CCl₄ in rats based on IL-6/JAK2/STAT3 signal pathway.A total of 60 SD rats were randomly divided into normal group,model group,silymarin group (120 mg/kg),and bergenin low,middle and high dose (20,40,80 mg/kg) groups with 10 rats in each group.Rats in silymarin group and bergenin groups were given intragastric administration according to 10 mL/kg,while normal group and model group were given corresponding volume of solvent once a day for a week.Two hours after the last administration,except the normal group,the other groups were intraperitoneally injected with 25% CCl₄ olive oil solution 2 mL/kg,to establish the rat model of acute liver injury.After fasting,the blood was taken from the eyeball and the liver was collected after 16 hours of fasting.The levels or activities of alanine transaminase(ALT),aspartate transaminase(AST),albumin(ALB),malondialdehyde (MDA),glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in serum were determined by biochemical method.The contents of interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in liver tissue were measured by enzyme-linked immunosorbent assay (ELISA).The pathological changes of liver tissue were observed by HE staining,and the expression level of IL-6 in liver tissue was observed by immunohistochemical (IHC).The protein expression levels of JAK2,p-JAK2,STAT3,p-STAT3,NF-κB p65 and p-NF-κB p65 were detected by Western blot.The results showed that inflammation,necrosis and IL-6 expression of liver tissue were reduced in different doses of bergenin and silymarin groups compared with model group,bergenin significantly reduced the activities or levels of ALT,AST,MDA in serum,TNF-α,IL-6 and IL-1β in liver tissue,up-regulated the activities or levels of ALB,SOD and GSH-Px in serum,and inhibited the expression of proteins related to IL-6/JAK2/STAT3 pathway.In conclusion,bergenin has a protective effect on acute liver injury induced by CCl₄ in rats,and the liver protection mechanism may be related to the inflammatory response and antioxidant mediated by IL-6/JAK2/STAT3 signaling pathway.

Key words: bergenin, acute liver injury, CCl₄, inflammatory response, IL-6/JAK2/STAT3 signal pathway

中图分类号: R965.1

蓝颖, 张可锋, 连苑宇, 陈俊杰, 杨超越, 王跃峰, 高雅. 基于IL-6/JAK2/STAT3信号通路研究岩白菜素对急性肝损伤大鼠的保护作用[J]. 天然产物研究与开发, 2021, 33(9): 1445-1451.

LAN Ying, ZHANG Ke-feng, LIAN Yuan-yu, CHEN Jun-jie, YANG Chao-yue, WANG Yue-feng, GAO Ya. Study on the protective effect of bergenin on acute liver injury in rats based on IL-6/JAK2/STAT3 signaling pathway[J]. NATURAL PRODUCT RESEARCH AND DEVELOPMENT, 2021, 33(9): 1445-1451.

[1]	沈锦煌, 冯是标, 杨娜娜, 马新华, 钟添华, 张永红. 畲药十二时辰总皂苷对CCl₄致小鼠肝纤维化的保护作用[J]. 天然产物研究与开发, 2023, 35(增刊1): 10-15.
[2]	马梦鸽, 宋忠兴, 陈琳, 唐志书, 孔鑫, 段金廒. 红花叶总黄酮提取纯化工艺优化及抗急性肝损伤活性研究[J]. 天然产物研究与开发, 2023, 35(1): 108-117.
[3]	韦磊, 王绚, 陈雄, 湛雯, 韩望. 汉黄芩素缓解高脂饮食喂养ApoE^-/-小鼠的动脉粥样硬化和NF-κB介导的动脉炎症反应[J]. 天然产物研究与开发, 2021, 33(5): 750-757.
[4]	刘睿, 邵瑾, 赵彤, 何蕾, 马慧萍, 景临林. 荠苧黄酮通过抑制氧化应激和炎症改善高原缺氧诱导的小鼠脑组织损伤[J]. 天然产物研究与开发, 2020, 32(8): 1413-1418.
[5]	李梓萌, 周僮, 高雅, 徐杰, 连苑宇, 冼红良, 李迎迎, 张可锋. 龙胆苦苷对大鼠肝纤维化Sonic Hedgehog信号通路的影响[J]. 天然产物研究与开发, 2020, 32(6): 946-952.
[6]	连苑宇, 徐杰, 朱田田, 马晓辉, 曹后康, 张可锋, 韦日明, 高雅. 基于SIRT6/NF-κB信号通路研究杠板归总黄酮对急性肝损伤大鼠的保护作用[J]. 天然产物研究与开发, 2020, 32(11): 1818-1825.
[7]	卢超, 石孟琼, 张媛媛, 罗恒, 陈腊年, 任俊红, 舒恒, 张继红. 芪苈参萸益心方通过减轻炎症反应、溶酶体功能和抑制NLRP3炎症小体激活来发挥对心肌梗死大鼠的保护作用 [J]. 天然产物研究与开发, 2020, 32(11): 1833-1843.
[8]	许琼梅, 高雅, 李梓萌, 韦日明, 马晓辉, 晋玲, 张可锋. 龙胆苦苷对非酒精性脂肪肝TLR-4/NF-κB和AMPK/Nrf2通路的影响[J]. 天然产物研究与开发, 2020, 32(10): 1652-1658.
[9]	董惠娟, 郭羽轩, 王鑫, 史浩楠, 刘涛, 赵军. 睡莲花总黄酮对CCl₄致小鼠肝纤维化的保护作用[J]. 天然产物研究与开发, 2020, 32(10): 1754-1760.
[10]	韩贵芳1，张长城1，陈茜1，马娜1，袁丁1,2，赵海霞1*. 淫羊藿总黄酮通过AMPK/SIRT1/NFκB信号通路减轻自然衰老大鼠睾丸组织炎症反应[J]. 天然产物研究与开发, 2018, 30(9): 1489-1493.
[11]	张可锋1,2，许琼梅1，曹后康1，陈春1，张帆1，李家妮1，晋玲2*. 七味净肝灵对酒精性肝损伤大鼠的保护作用研究[J]. 天然产物研究与开发, 2018, 30(8): 1306-1311.
[12]	葸博婷1，钟明利1，曹后康1，管玉满1，陈毅飞1，晋玲2，张可锋1,2. 金线风总黄酮对四氯化碳致急性肝损伤小鼠的保护作用及机制研究[J]. 天然产物研究与开发, 2018, 30(7): 1208-1213.
[13]	吴黉坦1,2，张友珍2，黄立森1,2，庞海月1,2，陈煜沛1,2，王贵弘1,2，叶子坚1，刘华欣3,4. 金边桑叶多酚提取物抗氧化及肝保护作用研究[J]. 天然产物研究与开发, 2018, 30(6): 944-950.
[14]	吴庆1 ，曹文富1,2*，马琳1，张永越1，田晟1，李荣亨3. 益气法制剂对CCL4所致肝纤维化大鼠TGF-β1/Smad信号通路的影响[J]. 天然产物研究与开发, 2018, 30(4): 634-639.
[15]	黄思茂1，高雅1，曹后康1，葸博婷1，王刚1，马冬梅1，张可锋1,2*. 过墙风总黄酮对四氯化碳致急性肝损伤小鼠的保护作用及机制研究[J]. 天然产物研究与开发, 2018, 30(2): 212-217.

基于IL-6/JAK2/STAT3信号通路研究岩白菜素对急性肝损伤大鼠的保护作用

Study on the protective effect of bergenin on acute liver injury in rats based on IL-6/JAK2/STAT3 signaling pathway

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价