Abstract:【Objective】 To invest the effect of human C- reactive protein on autophagy in acute kidney injury . 【Methods】 In order to induce the production of human CRP in mice, 25 μ g/mL body volume was injected intraperitoneally 2 hours before operation (body blood volume was equal to the gram weight of mice multiplied by 0.08 ) of anti CD32 antibody, then the acute renal ischemia-reperfusion injury model was established in mice. The mice were divided into Sham group, wild type mice group (CRP-Wt-I/R group) and transgenic mice expressing human CRP gene group(CRP-Tg-I/R group); the changes of CRP in mice before and after renal ischemia-reperfusion injury 2 hours before and 0h、24h、72h after operation were compared, Kidney specimens were obtained at 24 h and 72 h after operation. After HE staining, the pathological changes of renal tissue were observed, the expression of autophagy associated protein Beclin-1 was detected by immunohistochemical method, and the autophagy of renal tissue was observed under transmission electron microscope.【Results】 At 24 hours and 72 hours after renal ischemia-reperfusion injury, the expression of Beclin-1 protein in renal tubular epithelial cells of the CRP-Tg-I/R group decreased significantly (P<0.01), and no autophagy was observed.【Conclusion】 Human CRP down-regulated autophagy activity in renal tissue of AKI.
嵇金陵, 汤钱球, 张小云. CD32抗体诱导产生的人CRP对小鼠急性肾损伤自噬的研究[J]. 医学临床研究, 2018, 35(8): 1513-1516.
JIJin-ling, TANGQian-qiu, ZHANGXiao-yun. Effect of Human C- reactive Protein Induced by Anti-CD32 Antibody on Autophagy of Acute Kidney Injury in Mice. JOURNAL OF CLINICAL RESEARCH, 2018, 35(8): 1513-1516.
[1] Mohammad BI, Rahem AK, Hadi NR,et al. Reno-protective effects of TAK-242 on acute kidney injury in a rat model[J].2018 ,503(1):304-308. [2] Inoue K, Kuwana H, Shimamura Y, et al. Cisplatin-induced macroautophagy occurs prior to apoptosis in proximal tubules in vivo[J].Clin Exp Nephrol,2010,14(2):112-122. [3] Schwarze K, Kribben A, Ritter O, et al . Autophagy activation in circulating proangiogenic cells (PACs) aggravates AKI in type I diabetes mellitus[J].Am J Physiol Renal Physiol,2018. [Epub ahead of print]. [4] Chang NC,Nguyen M,Germain M,et al.Antagonism of Beclin 1-dependent utophagy by BCL-2 at the endoplasmic reticulum require NAF-1[J].EMBO J,2010,29( 3) : 606-618. [5] 冉燕. C反应蛋白与白蛋白比值可预测急性肾损伤患者的不良预后[A].中国免疫学会.第十二届全国免疫学学术大会摘要汇编[C].中国免疫学会,2017:1. [6] 戴玉婷,朱学涛.急性肾损伤患者治疗前后血清hs-CRP、IL-8和TNF-α水平检测的临床意义[J].吉林医学,2015,36(16):3554-3555. [7] Szalai AJ, McCrory MA. Varied biologic functions of C-reactive protein:lessons learned from transgenic mice[J].Immunol Res,2002,26(1-3):279-287. [8] Pepys MB, Baltz M, Gomer K,et al. Serum amyloid P-component is an acute-phase reactant in the mouse[J].Nature,1979 ,278(5701):259-261. [9] Ciliberto G, Arcone R, Wagner EF, et al. Inducible and tissue-specific expression of human C-reactive protein in transgenic mice[J].EMBO J,1987 ,6(13):4017-4022. [10] Tang Y, Huang XR, Lv J, et al. C-reactive protein promotes acute kidney injury by impairing G1/S-dependent tubular epithelium cell regeneration[J].Clin Sci (Lond),2014 ,126(9):645-659. [11] Pegues MA, McCrory MA, Zarjou A, et al. C-reactive protein exacerbates renal ischemia-reperfusion injury[J].Am J Physiol Renal Physiol,2013,304(11):F1358- F1365. [12] Ma S, Evans RG, Iguchi N,et al. Sepsis-induced acute kidney injury: A disease of the microcirculation[J].Microcirculation,2018,16:e12483. [13] Harrois A, Grillot N, Figueiredo S,et al. Acute kidney injury is associated with a decrease in cortical renal perfusion during septic shock[J].Crit Care,2018 ,22(1):161. [14] Kaushal GP, Shah SV. Autophagy in acute kidney injury[J].Kidney Int,2016 ,89(4):779-791. [15] Lai W, Tang Y, Huang XR, et al.C-reactive protein promotes acute kidney injury via Smad3-dependent inhibition of CDK2/cyclin E[J].Kidney Int,2016 ,90(3):610-626. [16] Wu Y, Zhang Y, Wang L,et al. The Role of Autophagy in Kidney Inflammatory Injury via the NF-κB Route Induced by LPS[J].Int J Med Sci,2015 ,12(8):655-667. [17] Herzog C, Yang C, Holmes A, et al. zVAD-fmk prevents cisplatin-induced cleavage of autophagy proteins but impairs autophagic flux and worsens renal function[J].Am J Physiol Renal Physiol,2012 ,303(8):F1239- F1250.