丹参酮IIA对CCl4诱导小鼠急性肝损伤的保护作用

doi:10.13418/j.issn.1001-165x.2022.6.08

中国临床解剖学杂志 ›› 2022, Vol. 40 ›› Issue (6): 671-676.doi: 10.13418/j.issn.1001-165x.2022.6.08

丹参酮IIA对CCl4诱导小鼠急性肝损伤的保护作用

李青青，熊佳慧，温玉清，杨红胜，李金斗，方萌，刘宇炜*

江汉大学医学院，武汉 430056

收稿日期:2022-06-30 出版日期:2022-11-25 发布日期:2022-12-12
通讯作者: 刘宇炜，医学博士,教授，E-mail：liuyuwei@jhun.edu.cn
作者简介:李青青(1996-)，女，福建福州人，硕士研究生，研究方向：肝纤维化作用机制及其治疗研究，E-mail：seyi-lee@163.com
基金资助:
国家自然科学基金面上项目(31371090)；湖北省卫生健康科研基金(WJ2021M217)；江汉大学2022年度大学生科研重点项目(2022zd053；2022zd059)

Protective effect of tanshinone IIA on CCl4-induced acute liver injury in mice

Li Qingqing, Xiong Jiahui, Wen Yuqing, Yang Hongsheng, Li Jindou, Fang Meng, Liu Yuwei*

School of Medicine, Jianghan University, Wuhan 430056, China

Received:2022-06-30 Online:2022-11-25 Published:2022-12-12

摘要/Abstract

摘要： 目的研究丹参酮IIA(tanshinone ⅡA, Tan ⅡA)对CCl4诱导小鼠急性肝损伤的抗氧化、保护作用及其可能的作用机制。方法将C57BL/6J小鼠随机分成正常组、CCl4组以及Tan ⅡA保护组(Tan ⅡA 20 mg/kg+CCl4)，每组10只。腹腔注射CCl4构建小鼠急性肝损伤模型。计算各组小鼠的肝脏指数，检测血清AST和ALT活性，测定肝组织SOD活性及GSH、MDA含量，HE染色观察肝组织病理变化，免疫组织化学法和Western blot检测肝组织PI3K、p-PI3K、Akt、p-Akt、Nrf2和HO-1蛋白表达水平。结果与CCl4组相比，Tan ⅡA保护组肝脏指数显著下降(P<0.01)，血清AST(P<0.01)和ALT活性降低(P<0.05)，肝组织SOD活性(P<0.01)及GSH含量升高(P<0.05)，MDA含量降低(P<0.05)，肝组织病理变化得到显著改善。同时，Tan ⅡA使肝组织p-PI3K和p-Akt表达水平明显升高(P<0.01)，显著诱导Nrf2转位入核(P<0.01)，促使其下游靶蛋白HO-1表达水平明显升高(P<0.01)。结论 Tan ⅡA能够显著改善CCl4诱导的急性肝损伤，其机制可能与PI3K/Akt/Nrf2/HO-1信号通路有关。

关键词: , 丹参酮IIA, , , 急性肝损伤, , , PI3K/Akt/Nrf2/HO-1通路, , , 抗氧化

Abstract: Objective To investigate the antioxidant and protective effect of tanshinone IIA (Tan ⅡA) on CCl4-induced acute liver injury in mice and its possible mechanism. Methods C57BL/6J mice were randomly divided into a control group, a CCl4 group and a Tan ⅡA protective group (Tan ⅡA 20 mg/kg+CCl4), with 10 mice in each group. Acute liver injury model was induced by intraperitoneal injection of CCl4 in mice. The liver indices were calculated, the activities of serum AST and ALT were detected, the activity of SOD and the contents of GSH and MDA in liver tissue were measured, and the pathological changes of liver tissue were observed by HE staining. The expression levels of PI3K, p-PI3K, Akt, p-Akt, Nrf2 and HO-1 proteins in liver tissue were detected by immunohistochemistry and Western blot. Results Compared with the CCl4 group, in the Tan ⅡA protective group, the liver indices was significantly decreased (P<0.01), the activities of serum AST (P<0.01) and ALT (P<0.05) was reduced, the activity of SOD (P<0.01) and the content of GSH (P<0.05) were increased while decreasing the content of MDA (P<0.05) in liver tissue, and the pathological changes of liver tissue was significantly improved. In addition, Tan ⅡA could significantly increase the expression levels of p-PI3K and p-Akt (P<0.01) in liver tissue, while significantly inducing Nrf2 translocation into nucleus (P<0.01), which significantly increased the expression level of its downstream target protein HO-1 (P<0.01). Conclusions Tan ⅡA can significantly ameliorate CCl4-induced acute liver injury. Its mechanism may be related to PI3K/Akt/Nrf2/HO-1 signaling pathway.

Key words: Tanshinone ⅡA, , , Acute liver injury, , , PI3K/Akt/Nrf2/HO-1 pathway, , , Antioxidation

中图分类号:

R285.5

李青青, 熊佳慧, 温玉清, 杨红胜, 李金斗, 方萌, 刘宇炜. 丹参酮IIA对CCl4诱导小鼠急性肝损伤的保护作用[J]. 中国临床解剖学杂志, 2022, 40(6): 671-676.

Li Qingqing, Xiong Jiahui, Wen Yuqing, Yang Hongsheng, Li Jindou, Fang Meng, Liu Yuwei. Protective effect of tanshinone IIA on CCl4-induced acute liver injury in mice[J]. Chinese Journal of Clinical Anatomy, 2022, 40(6): 671-676.

参考文献 17

[1]	Ammar H, Fontana RJ. The diagnosis and management of idiosyncratic drug-induced liver injury[J]. Liver Int, 2019, 39(1): 31-41. DOI: 10.1111/liv.13931.
[2]	Al-Harbi NO, Imam F, Naddem A, et al. Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin[J]. Int Immunopharmacol, 2014, 21(2):383-388. DOI: 10.1016/j.intimp. 2014. 05.014.
[3]	岳淑雯, 陈真. 急性肝损伤模型及信号通路研究进展[J]. 药学研究, 2019, 38(1): 49-52. DOI: 10.13506/j.cnki.jpr.2019.01.013.
[4]	Wu CT, Deng JS, Huang WC, et al. Salvianolic acid C against acetaminophen-induced acute liver injury by attenuating inflammation, oxidative stress, and apoptosis through inhibition of the Keap1/Nrf2/HO-1 signaling[J]. Oxid Med Cell Longev, 2019, 2019: 1-13. DOI: 10.1155/2019/9056845.
[5]	Zhang X, Kuang G, Wan J, et al. Salidroside protects mice against CCl4-induced acute liver injury via down-regulating CYP2E1 expression and inhibiting NLRP3 inflammasome activation[J]. Int Immunopharmacol, 2020, 85(6): 106662. DOI: 10.1016/j.intimp.2020.106662.
[6]	谢一潋, 杨乃彬, 王丽萍, 等. 姜黄素通过激活肝细胞自噬减轻脂多糖/D-氨基半乳糖诱导的大鼠急性肝损伤[J]. 中国病理生理杂志, 2020, 36(5): 860-864. DOI: 10.3969/j.issn.1000-4718.2020.05.013.
[7]	Liu Y, Wen P, Zhang X, et al. Breviscapine ameliorates CCl4-induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation[J]. Int J Mol Med, 2018, 42(2):755-768. DOI: 10.3892/ijmm.2018.3651.
[8]	关翠雯, 金晶, 李佳, 等. 丹参酮IIA激活Nrf2/ARE通路保护雷公藤甲素所致急性肝损伤[J]. 药学学报, 2013, 48(9): 1397-1402. DOI: 10.16438/j.0513-4870.2013.09.009.
[9]	Al-Dossari MH, Fadda LM, Attia HA, et al. Curcumin and selenium prevent lipopolysacch-aride/diclofenac-induced liver injury by suppressing inflammation and oxidative stress[J]. Biol Trace Elem Res, 2020, 196(1): 173-183. DOI: 10.1007/s12011-019-01910-4.
[10]	Weber LWD, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model[J]. Crit Rev Toxicol, 2003, 33(2): 105-136. DOI: 10.1080/713611034.
[11]	Ding C, Zhao Y, Chen X, et al. Taxifolin, a novel food, attenuates acute alcohol-induced liver injury in mice through regulating the NF-κB-mediated inflammation and PI3K/Akt signalling pathways[J]. Pharm Biol, 2021, 59(1): 868-879. DOI: 10.1080/13880209.2021.1942504.
[12]	王治博, 宋顺宗, 张子波. 黑米花色苷通过激活Nrf2/HO-1信号通路保护四氯化碳所致急性肝损伤的机制[J]. 时珍国医国药, 2019, 30(05): 1097-1100. DOI: 10.3969/j.issn.1008-0805.2019.05.022.
[13]	Rabie MA, Zaki HF, Sayed HM. Telluric acid ameliorates hepatic ischemia reperfusion-induced injury in rats: Involvement of TLR4, Nrf2, and PI3K/Akt signaling pathways[J]. Biochem Pharmacol, 2019, 168: 404-411. DOI: 10.1016/j.bcp.2019.08.001.
[14]	Jin Y, Tao X, Shi Y, et al. Salvianolic acid B exerts a protective effect in acute liver injury by regulating the Nrf2/HO-1 signaling pathway[J]. Can J Physiol Pharmacol, 2020, 98(3): 162-168. DOI: 10.1139/cjpp-2019-0349.
[15]	Guo F, Zhuang X, Han M, et al. Polysaccharides from enteromorpha prolifera protect against carbon tetrachloride-induced acute liver injury in mice via activation of Nrf2/HO-1 signaling, and suppression of oxidative stress, inflammation and apoptosis[J]. Food Funct, 2020, 11(5): 4485-4498. DOI: 10.1039/d0fo00575d.
[16]	Li J, Wang T, Liu P, et al. Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD[J]. Food Funct, 2021, 12(9): 3898-3918. DOI: 10.1039/d0fo02736g.
[17]	Lee C, Bak J, Yoon S, et al. Protective effect of oligonol on dimethylnitrosamine-induced liver fibrosis in rats via the JNK/NF-κB and PI3K/Akt/Nrf2 signaling pathways[J]. Antioxidants (Basel), 2021, 10(3): 366. DOI: 10.3390/antiox10030366.

丹参酮IIA对CCl4诱导小鼠急性肝损伤的保护作用

Protective effect of tanshinone IIA on CCl4-induced acute liver injury in mice

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 17

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	江剑宏, 段仁鹏, 李晓锋. 国人胆道三维重建解剖变异应用研究[J]. 中国临床解剖学杂志, 2024, 42(1): 1-4.
[2]	郭红志, 王瑜, 张加琪, 梁海彬, 马梓玮, 冯伟, 吴忧, 司子燚. 血管铸型结合CT三维模型评估先兆子痫胎盘血管结构[J]. 中国临床解剖学杂志, 2024, 42(1): 5-10.
[3]	李佳伟, 张静, 李灿然, 兰文杰, 籍庆余, 郭志勇, 张云凤, 刘启, 陈清威, 李筱贺. 蒙古族人群股骨近端解剖参数X线测量[J]. 中国临床解剖学杂志, 2024, 42(1): 11-16.
[4]	李琨, 张燕, 郭冉, 郝咪咪, 吴轩宇, 徐艺芳, 王超群, 马文童, 张灵淇, 杨宏宇, 李志军, 张少杰, 王星. 儿童及青少年枕颈角与后枕颈角数字化测量及其临床意义[J]. 中国临床解剖学杂志, 2024, 42(1): 17-20.
[5]	李文, 杨思艺, 黄蕾, 卿霁雯, 蒋松涛, 张磊. 基于MRI探讨Lisfranc韧带的形态学特点及临床意义[J]. 中国临床解剖学杂志, 2024, 42(1): 21-25.
[6]	李凡凡, 徐阳, 王晓旭. 紫草素调节Nrf2/HO-1信号通路对实验性大鼠肉芽肿性小叶性乳腺炎的治疗作用研究[J]. 中国临床解剖学杂志, 2024, 42(1): 26-32.
[7]	王兴航, 丁佳媛, 李放, 包翠芬, 阎丽菁. 人参皂苷Rg1通过抑制NLRP3炎症小体途径减轻氧糖剥夺/复供后小胶质细胞炎症反应[J]. 中国临床解剖学杂志, 2024, 42(1): 33-41.
[8]	程莹莹, 武建军, 蔡海燕, 焦旭文, 马江波, 丁银秀. 体外炎性诱导星形胶质细胞激活及功能分析[J]. 中国临床解剖学杂志, 2024, 42(1): 42-46.
[9]	祁志, 杨力, 贾秋叶, 陈浩伦, 段兆达, 吴春云. 依达拉奉经MAPKs通路对脂多糖激活的小胶质细胞Sirt3表达调控[J]. 中国临床解剖学杂志, 2024, 42(1): 47-53.
[10]	张晶晶, 王洪新. 黄芩苷通过PDGF/P38 MAPK信号通路对肺动脉高压大鼠的保护作用[J]. 中国临床解剖学杂志, 2024, 42(1): 54-58.
[11]	乐钦, 陈荣丽, 熊婧熙, 王婷怡, 蔡志恒, 易秋实, 曾心怡. 白芨多糖对大鼠跨区皮瓣choke区的影响[J]. 中国临床解剖学杂志, 2024, 42(1): 59-64.
[12]	李笑予, 张磊, 付磊, 李东波, 汪国友. 三步接骨法治疗Sanders Ⅱ型跟骨骨折的有限元研究[J]. 中国临床解剖学杂志, 2024, 42(1): 65-70.
[13]	吴研飞, 马剑雄, 卢斌, 王颖, 柏豪豪, 靳洪震, 马信龙. CT后处理技术重建CT值与终板抗压强度的相关性研究[J]. 中国临床解剖学杂志, 2024, 42(1): 71-76.
[14]	庄万强, 唐毅, 骆勇刚, 张辉. 关节镜联合胫骨高位截骨术对髌骨位置及髌股关节功能影响的早中期回顾性研究[J]. 中国临床解剖学杂志, 2024, 42(1): 77-82.
[15]	罗鹰, 窦伟誉, 吴小杭, 陈璟昆, 彭昌贵, 潘剑英 . 微创海马钢板内固定治疗跟骨骨折并发症的影响因素[J]. 中国临床解剖学杂志, 2024, 42(1): 83-88.