A study on preventive mechanisms of resveratrol on injuried heart during hepatic ischemia/reperfusion injury in rats by regulating Notch signaling pathway

doi:10.13459/j.cnki.cjap.2016.04.017

Abstract

Abstract: Objective:To study the role of Notch1 signaling pathway in the myocardial protective effects of resveratrol pro-treatment after hepatic ischemia/reperfusion injury. Methods:Thirty-six healthy male SD rats were randomly divided into 3 groups:sham control (SC) group, hepatic ischemic/reperfusion (HIR) group, and pro-treatment resveratrol (Res) group,12 rats in each group. After each group with hepatic ischemia 40 min reperfusion 2 h (SC group placing equal time), the left ventricular function including left ventricular pressure (LVP), left ventricular systolic pressure (LVSP) and its derivate (±dp/dt) was measured; the serum activities of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) and tumor necrosis factorα(TNF-α) and interleukin-6(IL-6) were detected. The activity of myocardial su-peroxide dismutase(SOD) and contents of myocardial malonaldehyde (MDA) were determined; Notch intracellular domain (NICD) expressions were detected with Western blot; the mRNA levels of Notch1 and TNF-αwere detected by real-time PCR. Results:Compared with SC group, the left ventricular functions in the HIR group were significantly decreased. With decreasing the expression of NICD and Notchl, the activities of CK-MB, LDH, TNF-αand IL-6 in the serum were evidently increased(P<0.01), the activity of SOD in myocardum was decreased and contents of MDA in myocardum was enhanced (P<0.01). Compared with HIR group, the left ventricular functions were significantly en-hanced in Res group (P<0.01). The above mentioned parameters in the serum in the Res group were evidently improved (P<0.01), meanwhile the expression of NICD and Notchl were significantly enhanced whereas the expression of TNF-α was obviously decreased. Conclusion:The findings indicate that resveratrol has protective effect on myocardial injury during the hepatic ischemia/reperfusion, and its mecha-nisms may be related to anti-inflammation and anti-oxidative stress via Notch signaling pathway.

Key words: hepatic ischemia/reperfusion injury, resveratrol, Notch signaling pathway, inflammation, oxidative stress

LU Yan-zhen, WANG Jia, SONG Juan, LI Bao-hong, GUO Ya-ling, WANG Dong, ZHANG Cui-ying. A study on preventive mechanisms of resveratrol on injuried heart during hepatic ischemia/reperfusion injury in rats by regulating Notch signaling pathway[J]. CJAP, 2016, 32(4): 351-355.

References

[1] Dogan S, Aslan M. Hepatic ischemia-reperfusion injury and therapeutic strategies to alleviate cellular damage[J]. Hepatol Res, 2011, 41(2):103-117.
[2] Kuboki S, Shin T, Huber N, et al. Hepatocyte signaling through CXC chemokine receptor-2 is detrimental to liver re-covery after ischemia/reperfusion in mice[J]. Hepatology, 2008, 48(4):1213-1223.
[3] Li T, Zhao JM, Zhang Y, et al. Suppression of acute rejec-tive response following orthotopic liver transplantation in ex-perimental rats infected with Echinococcus multilocularis[J]. Chin Med J(Engl), 2011, 124(18):2818-2823.
[4] Li Y, Liu NF, Gu ZZ, et al. Coronary tortuosity is associat-ed with reversible myocardial perfusion defects in patients without coronary artery disease[J]. Chin Med J (Engl), 2012, 125(19):3581-3583.
[5] 马小娟, 王红梅, 张建龙, 等. 大鼠肝缺血再灌注损伤对心脏能量代谢和结构的影响及其机制[J]. 中国病理生理杂志, 2008, 24(7):1297-1301.
[6] Li H, Forstermann U. Red wine and cardiovascular health[J]. Circ Res, 2012, 111(8):959-961.
[7] Lamont KT, Somers S, Lacerda L, et al. Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol-and melatonin-induced cardioprotection[J]. J Pineal Res, 2011, 50(4):374-380.
[8] 孙玮明, 郑鸣之, 应磊, 等. 白藜芦醇在大鼠离体心脏低温保存中的保护作用及其机制[J]. 中国应用生理学杂志, 2014, 30(4):348-351.
[9] Zhou XL, Liu JC. Role of Notch signaling in the mammalian heart[J]. Braz J Med Biol Res, 2014, 47(1):1-10.
[10] Croquelois A, Domenighetti AA, Nemir M, et al. Control of the adaptive response of the heart to stress via the Notch1 re-ceptor pathway[J]. J Exp Med, 2008, 205(13):3173-3185.
[11] 杨阳, 段维勋, 王宁, 等. γ-分泌酶抑制剂对大鼠离体心脏缺血再灌注损伤的作用[J]. 中国体外循环杂志, 2013, 11(1):41-44.
[12] 杨阳, 金振晓, 段维勋, 等. 缺血再灌注前后人心肌组织中Notch信号通路相关分子的变化[J]. 中国体外循环杂志, 2010, 8(4):236-238.
[13] Gude NA, Emmanuel G, Wu W, et al. Activation of Notch-mediated protective signaling in the myocardium[J]. Circ Res, 2008, 102(9):1025-1035.
[14] Zhou XL, Wan L, Xu QR, et al. Notch signaling activation contributes to cardioprotection provided by ischemic precondi-tioning and postconditioning[J]. J Transl Med, 2013, 11:251.
[15] Yu HC, Qin HY, He F, et al. Canonical Notch pathway protects hepatocytes from ischemia/reperfusion injury in mice by repressing reactive oxygen species production through JAK2/STAT3 signaling[J]. Hepatology, 2011, 25(3):979-988.
[16] Bheeshmachar G, Purushotaman D, Sade H, et al. Evi-dence for a role for notch signaling in the cytokine-dependent survival of activated T cells[J]. J Immunol, 2006, 177(8):5041-5050.