Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (7): 21-27.doi: 10.6040/j.issn.1671-7554.0.2017.493

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Protective effects of DRSAb on ischemia reperfusion induced renal injury in rats

SUN Jingjing, ZHANG Jiangwei, KUANG Peidan, ZHANG Ying, XUE Wujun, ZHENG Jin   

  1. Department of Kidney Transplant, First Affiliated Hospital of Xian Jiaotong University, Xian 710061, Shaanxi, China
  • Published:2022-09-27

Abstract: Objective To explore the protective effects of Na+/K+-ATPase DR region specific antibody(DRSAb)on ischemia/reperfusion induced renal injury and its mechanism. Methods Spragur-Dawley(SD)male rats were immunized with synthesised DR region peptides to prepare DRSAb. The biological activity of DRSAb was detected with Western blotting, and the mechanism of cell signal transduction was determined with flow cytometry. The activity of HK-2 cells was assessed with MTT. The protective effect of DRSAb on ischemia-reperfusion injury in rat kidney was evaluated with animal models of ischemia-reperfusion injury. Results The results showed that 90.02% of HK-2 cells could bind with DRSAb. The DRSAb immune sera could significantly enchance the tolerance of HK-2 cells to hypoxia, compared with control seara(OD: 0.50±0.03 vs 0.10±0.02, P<0.001). DRSAb could activate PI3K/AKT and PKCε kinase(P<0.001), which could be inhibited by LY294002 and PEAVSLKPT(P<0.001). Animal experiments indicated that DRSAb group demonstrated a significant improvement in renal function with a lower serum creatinine(sCr)and blood urea nitrogen(BUN)levels 3-6 days postoperative compared with the Control group(P<0.001). Histological evaluation showed that the Control group had visible vascular congestion, epithelial cell swelling and extensive tubular necrosis. 山 东 大 学 学 报 (医 学 版)56卷7期 -孙晶晶,等. DRSAb对缺血再灌注损伤大鼠肾脏的保护作用 \=-However, DRSAb group only had slight vascular congestion, mild epithelial cell edema, and no tubular necrosis. Conclusion DRSAb has protective effects against renal ischemia/reperfusion injury in rats, which is associated with the activiation of PI3K/AK and PKCε signalling pathways.

Key words: Ischemia/reperfusion, Na+/K+-ATPase, DR region specific antibody, PI3K/AKT, PKCε

CLC Number: 

  • R392.7
[1] Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment [J]. J Renal Inj Prev, 2015, 4(2): 20-27.
[2] Yue TL, Wang C, Gu JL, et al. Inhibition of extracellular signal-regulated kinase enhances Ischemia/Reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart[J]. Circ Res, 2000, 86(6): 692-699.
[3] Huang P, Sun Y, Yang J, et al. The ERK1/2 signaling pathway is involved in sulfur dioxide preconditioning-induced protection against cardiac dysfunction in isolated perfused rat heart subjected to myocardial ischemia/reperfusion[J]. Int J Mol Sci, 2013, 14(11): 22190-22201.
[4] Hausenloy DJ, Yellon DM. Survival kinases in ischemic preconditioning and postconditioning[J]. Cardiovasc Res, 2006,70(2): 240-253.
[5] Yao H, Han X, Han X. The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway[J]. Am J Cardiovasc Drugs, 2014, 14(6): 433-442.
[6] 易善红. 人促红细胞生成素对肾脏缺血再灌注的保护作用[J]. 免疫学杂志, 2007, 23(1): 49-51. YI Shanhong. Protective activity of human erythropoietin against renal ischemia-reperfusion injury[J]. Immunological Journal, 2007, 23(1): 49-51.
[7] Zheng J, Koh X, Hua F, et al. Cardioprotection induced by Na+/K+ ATPase activation involves extracellular Signal regulated kinase1/2 and phosphoinositide 3-kinase /AKT pathway[J]. Cardiovasc Res, 2011, 89(1): 51-59.
[8] Gong HL, Sun JJ, Xue WJ, et al. Protective effect of truncated Na+/K+-ATPase b on ischemia/reperfusion-induced renal injury in rats [J]. Exp Biol Med(Maywood), 2014,239(6):677-685.
[9] Aizman O, Aperia A. Na(+)/K(+)-ATPase as a signal transducer[J]. Ann N Y Acad Sci, 2003, 986(1): 489-496.
[10] Xu KY, Takimoto E, Fedarko NS. Activation of(Na+/+ K+)-ATPase induces positive inotropy in intact mouse heart in vivo[J]. Biochem Biophys Res Commun, 2006, 349(2): 582-587.
[11] Guerreroorriach JL, Belmonte JJE, Fernandez AR, et al. Cardioprotection with halogenated gases: how does it occur? [J]. Drug Des Devel Ther, 2017, 16(11): 837-849.
[12] Lee SG, Su ZZ, Emdad L, et al. Astrocyte elevated gene-1 activates cell survival pathways through PI3K-Akt signaling [J]. Oncogene, 2008, 27(8): 1114-1121.
[13] Ma ZG, Xia HQ,Cui SL, et al. Attenuation of renal ischemic reperfusion injury by salvianolic acid B via suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway [J]. Braz J Med Biol Res, 2017, 50(6): e5954. doi: 10.1590/1414-431X20175954.
[14] Chen XD, Su MY, Chen TT, et al. Oxidative stress affects retinal pigment epithelial cell survival through epidermal growth factor receptor/AKT signaling pathway[J]. Int J Ophthalmol, 2017, 10(4): 507-514.
[15] Guo XQ, Cao YL, Hao F, et al. Tangeretin alters neuronal apoptosis and ameliorates the severity of seizures in experimental epilepsy-induced rats by modulating apoptotic protein expressions, regulating matrix metalloproteinases, and activating the PI3K/Akt cell survival pathway [J]. Adv Med Sci, 2017, 62(2): 246-253.
[16] Yao H, Han X, Han X. The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway [J]. Am J Cardiovasc Drugs, 2014, 14(6): 433-442.
[17] Madonna R, Bolli R, Rokosh G, et al. Targeting phosphatidylinositol 3-kinase-Akt through hepatocyte growth factor for cardioprotection [J]. J Cardiovasc Med, 2013, 14(4): 249-253.
[18] Yu ZH, Cai M, Xiang J, et al. PI3K/Akt pathway contributes to neuroprotective effect of Tongxinluo against focal cerebral ischemia and reperfusion injury in rats [J]. J Ethnopharmacol, 2016, 2(181): 8-19.
[19] Peng Y, Pu J, Tang C, et al. Curcumin inhibits heat-induced apoptosis by suppressing NADPH oxidase 2 and activating theAkt/mTOR signaling pathway in bronchial epithelial cells[J]. Cell Physiol Biochem, 2017, 41(5): 2091-2103.
[20] Antal CE, Newton AC. Tuning the signaling output of protein kinase C.[J]. Biochem Soc Trans, 2014, 42(6): 1477-1483.
[21] Kang JH, Toita R, Kim CW, et al. Protein kinase C(PKC)isozyme-specific substrates and their design[J]. Biotechnol Adv, 2012, 30(6): 1662-1672.
[22] Newton AC, Antal CE, Steinberg SF. Protein kinase C mechanisms that contribute to cardiac remodeling[J]. Clin Sci, 2016, 130(17): 1499-1510.
[23] Ferreira JC, Brum PC, Mochly-Rosen D.βIIPKC and εPKC isozymes as potential pharmacological targets in cardiac hypertrophy and heart failure [J]. J Mol Cell Cardiol, 2011, 51(4): 479-484.
[24] Newton AC, Brognard J. Reversing the paradigm:protein kinase C as a tumor suppressor[J]. Trends Pharmacol Sci, 2017, 38(5): 438-447.
[25] Simkhovich BZ, Przyklenk K, Kloner RA. Role of protein kinase C in ischemic “conditioning”: from first evidence to current perspectives[J]. J Cardiovasc Pharmacol Ther, 2013, 18(6): 525-532.
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