Protective effect and mechanism of tanshinone <b>Ⅱ</b> A on liver ischemia-reperfusion injury in mouse_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Wenping , ZHANG Yongchuan ,  ZHANG Yinglin

Department of Hepatopancreatobiliary Surgery, The Third Hospital of Mianyang(Sichuan Mental Health Center), Mianyang, Sichuan 621000, P. R. China;

Corresponding author：

ZHANG Yinglin, Email: zhangyinglin2018@126.com

Keywords：

tanshinone ⅡA; ischemia-reperfusion injury; high mobility group box 1; advanced glycosylation end-product specific receptor; Toll like receptor 4

DOI：

10.7507/1007-9424.201907023

Video：

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Objective To observe the protective effect of tanshinone Ⅱ A on the mouse liver ischemia-reperfusion injury (IRI) model and preliminarily explore its mechanism of alleviating liver injury.Methods The IRI mouse model was established after the pre-treating with tanshinone Ⅱ A. Then, the serum and liver tissue of mice were collected to detect the changes of liver function, histopathology, liver cell apoptosis, and inflammatory factors. In addition, the protein expression levels of high mobility group box 1 (HMGB1), advanced glycosylation end-product specific receptor (RAGE), and Toll like receptor 4 (TLR4) in the liver tissues were detected by the Western blot method.Results All data were analyzed by the homogeneity of variance test. The results of factorial design showed that the levels of ALT and AST in the serum, the pathological score and apoptosis index, the inflammatory response, as well as the expressions of HMGB1, TLR4 and RAGE proteins in the liver tissues were decreased significantly (P<0.05) in the sham operatation plus tanshinone Ⅱ A mice, which were increased significantly (P<0.05) in the IRI mice, which were antagonized synergistically by the tanshinone ⅡA and IRI (P<0.05).Conclusions Tanshinone ⅡA could reduce the liver IRI and inflammatory response in mouse. These effects might be related to the down-regulations of TLR4, HMGB1, and RAGE expressions.

Citation： LIU Wenping, ZHANG Yongchuan, ZHANG Yinglin. Protective effect and mechanism of tanshinone Ⅱ A on liver ischemia-reperfusion injury in mouse. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(3): 298-303. doi: 10.7507/1007-9424.201907023 Copy

1.	Zhan C, Dai X, Shen G, et al. Preoperative short-term fasting protects liver injury in patients undergoing hepatectomy. Ann Transl Med, 2018, 6(23): 449.
2.	Jassem W, Xystrakis E, Ghnewa YG, et al. Normothermic machine perfusion (NMP) inhibits proinflammatory responses in the liver and promotes regeneration. Hepatology, 2019, 70(2): 682-695.
3.	金光鑫, 乔鹏飞, 胡彦华, 等. 同种异体骨髓间充质干细胞保护大鼠肝脏热缺血再灌注损伤的研究. 中国普外基础与临床杂志, 2013, 20(1): 60-65.
4.	Yang Y, Liu L, Zhang X, et al. Tanshinone Ⅱ A prevents rifampicin-induced liver injury by regulating BSEP/NTCP expression via epigenetic activation of NRF2. Liver Int, 2019 Sep 30. doi: 10.1111/liv.14262.
5.	Li X, Wu Y, Zhang W, et al. Pre-conditioning with tanshinone Ⅱ A attenuates the ischemia/reperfusion injury caused by liver grafts via regulation of HMGB1 in rat Kupffer cells. Biomed Pharmacother, 2017, 89: 1392-1400.
6.	Bastos-Neves D, Salvalaggio PRO, Almeida MD. Risk factors, surgical complications and graft survival in liver transplant recipients with early allograft dysfunction. Hepatobiliary Pancreat Dis Int, 2019 Feb 25. pii: S1499-3872(19)30032-3.
7.	Ze X, Jia J, Li X, et al. Tanshinone Ⅱ A promotes the proliferation of WB-F344 hepatic oval cells via Wnt/β-catenin signaling. Mol Med Rep, 2016, 13(2): 1501-1508.
8.	Qin F, Ma Y, Li X, et al. Efficacy and mechanism of tanshinone Ⅱ A liquid nanoparticles in preventing experimental postoperative peritoneal adhesions in vivo and in vitro. Int J Nanomedicine, 2015, 10: 3699-3716.
9.	Meng Z, Si CY, Teng S, et al. Tanshinone Ⅱ A inhibits lipopolysaccharide-induced inflammatory responses through the TLR4/TAK1/NF-κB signaling pathway in vascular smooth muscle cells. Int J Mol Med, 2019, 43(4): 1847-1858.
10.	Quan M, Lv Y, Dai Y, et al. Tanshinone Ⅱ A protects against lipopolysaccharide-induced lung injury through targeting Sirt1. J Pharm Pharmacol, 2019, 71(7): 1142-1151.
11.	Xiong CQ, Zhou HC, Wu J, et al. The protective effects and the involved mechanisms of tanshinone Ⅱ A on sepsis-induced brain damage in mice. Inflammation, 2019, 42(1): 354-364.
12.	苏慕霞, 谭苑芬, 叶冰. 总丹参酮抑制 LPS 诱导巨噬细胞炎症反应的作用机制研究. 中药材, 2018, 41(4): 986-989.
13.	Pan Y, Qian JX, Lu SQ, et al. Protective effects of tanshinone Ⅱ A sodium sulfonate on ischemia-reperfusion-induced myocardial injury in rats. Iran J Basic Med Sci, 2017, 20(3): 308-315.
14.	Xu YM, Ding GH, Huang J, et al. Tanshinone Ⅱ A pretreatment attenuates ischemia/reperfusion-induced renal injury. Exp Ther Med, 2016, 12(4): 2741-2746.
15.	刘月秋, 刘辉. 丹参酮 Ⅱ A 对大鼠脑缺血再灌注损伤的作用及机制研究. 中国中医急症, 2016, 25(12): 2283-2285, 2295.
16.	Wang Y, Ni Q, Ye Q, et al. Tanshinone Ⅱ A activates autophagy to reduce liver ischemia-reperfusion injury by MEK/ERK/mTOR pathway. Pharmazie, 2018, 73(7): 396-401.
17.	Gao M, Ou H, Jiang Y, et al. Tanshinone Ⅱ A attenuates sepsis-induced immunosuppression and improves survival rate in a mice peritonitis model. Biomed Pharmacother, 2019, 112: 108609.
18.	Meng ZJ, Wang C, Meng LT, et al. Sodium tanshinone Ⅱ A sulfonate attenuates cardiac dysfunction and improves survival of rats with cecal ligation and puncture-induced sepsis. Chin J Nat Med, 2018, 16(11): 846-855.
19.	Yu R, Jiang S, Tao Y, et al. Inhibition of HMGB1 improves necrotizing enterocolitis by inhibiting NLRP3 via TLR4 and NF-κB signaling pathways. J Cell Physiol, 2019, 234(8): 13431-13438.
20.	栾正刚, 郭仁宣. HMGB1 mRNA 表达对急性坏死性胰腺炎大鼠肠黏膜 ZO-1 mRNA 及其蛋白表达的影响. 中国普外基础与临床杂志, 2013, 20(3): 265-270.
21.	王国良, 兑丹华, 白亮, 等. TAP 诱导大鼠胰腺腺泡细胞释放 HMGB1 的研究. 中国普外基础与临床杂志, 2012, 19(10): 1074-1078.
22.	Sherif IO, Al-Shaalan NH. Vildagliptin attenuates hepatic ischemia/reperfusion injury via the TLR4/NF-κB signaling pathway. Oxid Med Cell Longev, 2018, 2018: 3509091.
23.	Ekanayaka SA, McClellan SA, Peng X, et al. HMGB1 antagonist, box A, reduces TLR4, RAGE, and inflammatory cytokines in the cornea of P. aeruginosa-infected mice. J Ocul Pharmacol Ther, 2018 Nov 8. doi: 10.1089/jop.2018.0073.
24.	Deng M, Tang Y, Li W, et al. The endotoxin delivery protein HMGB1 mediates caspase-11-dependent lethality in sepsis. Immunity, 2018, 49(4): 740-753.
25.	Yang H, Liu H, Zeng Q, et al. Inhibition of HMGB1/RAGE-mediated endocytosis by HMGB1 antagonist box A, anti-HMGB1 antibodies, and cholinergic agonists suppresses inflammation. Mol Med, 2019, 25(1): 13.

1. Zhan C, Dai X, Shen G, et al. Preoperative short-term fasting protects liver injury in patients undergoing hepatectomy. Ann Transl Med, 2018, 6(23): 449.
2. Jassem W, Xystrakis E, Ghnewa YG, et al. Normothermic machine perfusion (NMP) inhibits proinflammatory responses in the liver and promotes regeneration. Hepatology, 2019, 70(2): 682-695.
3. 金光鑫, 乔鹏飞, 胡彦华, 等. 同种异体骨髓间充质干细胞保护大鼠肝脏热缺血再灌注损伤的研究. 中国普外基础与临床杂志, 2013, 20(1): 60-65.
4. Yang Y, Liu L, Zhang X, et al. Tanshinone Ⅱ A prevents rifampicin-induced liver injury by regulating BSEP/NTCP expression via epigenetic activation of NRF2. Liver Int, 2019 Sep 30. doi: 10.1111/liv.14262.
5. Li X, Wu Y, Zhang W, et al. Pre-conditioning with tanshinone Ⅱ A attenuates the ischemia/reperfusion injury caused by liver grafts via regulation of HMGB1 in rat Kupffer cells. Biomed Pharmacother, 2017, 89: 1392-1400.
6. Bastos-Neves D, Salvalaggio PRO, Almeida MD. Risk factors, surgical complications and graft survival in liver transplant recipients with early allograft dysfunction. Hepatobiliary Pancreat Dis Int, 2019 Feb 25. pii: S1499-3872(19)30032-3.
7. Ze X, Jia J, Li X, et al. Tanshinone Ⅱ A promotes the proliferation of WB-F344 hepatic oval cells via Wnt/β-catenin signaling. Mol Med Rep, 2016, 13(2): 1501-1508.
8. Qin F, Ma Y, Li X, et al. Efficacy and mechanism of tanshinone Ⅱ A liquid nanoparticles in preventing experimental postoperative peritoneal adhesions in vivo and in vitro. Int J Nanomedicine, 2015, 10: 3699-3716.
9. Meng Z, Si CY, Teng S, et al. Tanshinone Ⅱ A inhibits lipopolysaccharide-induced inflammatory responses through the TLR4/TAK1/NF-κB signaling pathway in vascular smooth muscle cells. Int J Mol Med, 2019, 43(4): 1847-1858.
10. Quan M, Lv Y, Dai Y, et al. Tanshinone Ⅱ A protects against lipopolysaccharide-induced lung injury through targeting Sirt1. J Pharm Pharmacol, 2019, 71(7): 1142-1151.
11. Xiong CQ, Zhou HC, Wu J, et al. The protective effects and the involved mechanisms of tanshinone Ⅱ A on sepsis-induced brain damage in mice. Inflammation, 2019, 42(1): 354-364.
12. 苏慕霞, 谭苑芬, 叶冰. 总丹参酮抑制 LPS 诱导巨噬细胞炎症反应的作用机制研究. 中药材, 2018, 41(4): 986-989.
13. Pan Y, Qian JX, Lu SQ, et al. Protective effects of tanshinone Ⅱ A sodium sulfonate on ischemia-reperfusion-induced myocardial injury in rats. Iran J Basic Med Sci, 2017, 20(3): 308-315.
14. Xu YM, Ding GH, Huang J, et al. Tanshinone Ⅱ A pretreatment attenuates ischemia/reperfusion-induced renal injury. Exp Ther Med, 2016, 12(4): 2741-2746.
15. 刘月秋, 刘辉. 丹参酮 Ⅱ A 对大鼠脑缺血再灌注损伤的作用及机制研究. 中国中医急症, 2016, 25(12): 2283-2285, 2295.
16. Wang Y, Ni Q, Ye Q, et al. Tanshinone Ⅱ A activates autophagy to reduce liver ischemia-reperfusion injury by MEK/ERK/mTOR pathway. Pharmazie, 2018, 73(7): 396-401.
17. Gao M, Ou H, Jiang Y, et al. Tanshinone Ⅱ A attenuates sepsis-induced immunosuppression and improves survival rate in a mice peritonitis model. Biomed Pharmacother, 2019, 112: 108609.
18. Meng ZJ, Wang C, Meng LT, et al. Sodium tanshinone Ⅱ A sulfonate attenuates cardiac dysfunction and improves survival of rats with cecal ligation and puncture-induced sepsis. Chin J Nat Med, 2018, 16(11): 846-855.
19. Yu R, Jiang S, Tao Y, et al. Inhibition of HMGB1 improves necrotizing enterocolitis by inhibiting NLRP3 via TLR4 and NF-κB signaling pathways. J Cell Physiol, 2019, 234(8): 13431-13438.
20. 栾正刚, 郭仁宣. HMGB1 mRNA 表达对急性坏死性胰腺炎大鼠肠黏膜 ZO-1 mRNA 及其蛋白表达的影响. 中国普外基础与临床杂志, 2013, 20(3): 265-270.
21. 王国良, 兑丹华, 白亮, 等. TAP 诱导大鼠胰腺腺泡细胞释放 HMGB1 的研究. 中国普外基础与临床杂志, 2012, 19(10): 1074-1078.
22. Sherif IO, Al-Shaalan NH. Vildagliptin attenuates hepatic ischemia/reperfusion injury via the TLR4/NF-κB signaling pathway. Oxid Med Cell Longev, 2018, 2018: 3509091.
23. Ekanayaka SA, McClellan SA, Peng X, et al. HMGB1 antagonist, box A, reduces TLR4, RAGE, and inflammatory cytokines in the cornea of P. aeruginosa-infected mice. J Ocul Pharmacol Ther, 2018 Nov 8. doi: 10.1089/jop.2018.0073.
24. Deng M, Tang Y, Li W, et al. The endotoxin delivery protein HMGB1 mediates caspase-11-dependent lethality in sepsis. Immunity, 2018, 49(4): 740-753.
25. Yang H, Liu H, Zeng Q, et al. Inhibition of HMGB1/RAGE-mediated endocytosis by HMGB1 antagonist box A, anti-HMGB1 antibodies, and cholinergic agonists suppresses inflammation. Mol Med, 2019, 25(1): 13.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Protective effect and mechanism of tanshinone Ⅱ A on liver ischemia-reperfusion injury in mouse

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