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远程肢体缺血预处理(rIPC)可激活抗氧化和抗凋亡基因,并抑制肾缺血/再灌注损伤中的促炎细胞因子基因。

Remote limb ischemic preconditioning (rIPC) activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in renal ischemia/reperfusion injury.

作者信息

Hussein Abdelaziz M, Harraz Ahmed M, Awadalla Amira, Barakat Nashwa, Khater Shery, Shokeir Ahmed A

机构信息

Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

出版信息

Gen Physiol Biophys. 2016 Jan;35(1):77-86. doi: 10.4149/gpb_2015035. Epub 2015 Nov 27.

Abstract

The mechanisms underlying the renoprotective effect for remote limb ischemic preconditioning (rIPC) against renal ischemia/reperfusion injury need further elucidation. In our work, one hundred and twenty male Sprague Dawley rats were randomized into 3 groups; sham, I/R group (left renal 45 min ischemia) and rIPC (as I/R group with 3 cycles of left femoral ischemic PC just before renal ischemia). Rats were sacrificed at 2 h, 24 h, 48 h and 7 days. Serum creatinine and urea were measured at the baseline and endpoints. Also, histopathological examination and assessment of the expression of inflammatory cytokines e.g. TNF-α, IL-1β and ICAM-1 and antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 in left kidney were done by the end of experiment. The results of this study demonstrated that, rIPC caused significant improvement in serum creatinine and BUN levels and in the expression of antioxidant genes and Bcl-2 antiapoptotic gene with significant attenuation of pro-inflammatory cytokines and histopathological damage score at all-time points compared to I/R group (p ≤ 0.05). In conclusion, inhibition of inflammatory cytokine (TNF-α, IL-1β and ICAM-1) formation and activation of antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 could be possible underlying mechanisms for the renoprotective effect of rIPC.

摘要

远程肢体缺血预处理(rIPC)对肾缺血/再灌注损伤的肾脏保护作用的潜在机制需要进一步阐明。在我们的研究中,120只雄性Sprague Dawley大鼠被随机分为3组;假手术组、I/R组(左肾缺血45分钟)和rIPC组(同I/R组,但在肾缺血前对左股动脉进行3个周期的缺血预处理)。分别在2小时、24小时、48小时和7天时处死大鼠。在基线和各终点测量血清肌酐和尿素。此外,在实验结束时对左肾进行组织病理学检查,并评估炎性细胞因子如TNF-α、IL-1β和ICAM-1以及抗氧化基因Nrf2、HO-1和NQO-1和抗凋亡基因Bcl-2的表达。本研究结果表明,与I/R组相比,rIPC在所有时间点均能显著改善血清肌酐和BUN水平,以及抗氧化基因和Bcl-2抗凋亡基因的表达,同时显著减轻促炎细胞因子水平和组织病理学损伤评分(p≤0.05)。总之,抑制炎性细胞因子(TNF-α、IL-1β和ICAM-1)的形成以及激活抗氧化基因Nrf2、HO-1和NQO-1以及抗凋亡基因Bcl-2可能是rIPC肾脏保护作用的潜在机制。

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