白藜芦醇通过调节SIRT1/NF-κB通路减轻力竭训练致大鼠肾的炎症反应

Resveratrol Reduces Renal Inflammatory Response Induced by Exhaustive Exercise in Rats by Regulating SIRT1/NF-κB Pathway

白藜芦醇是天然存在的沉默信息调节因子2相关酶1(sirtuin1,SIRT1)小分子激动剂,其肾的保护作用已在多种肾疾病动物模型中得到了验证。然而,白藜芦醇是否能够改善力竭训练导致的大鼠肾损伤,以及是否通过SIRT1/NF-κB信号通路调节运动性肾损伤大鼠肾炎症反应,尚缺乏系统研究。本研究将32只SD大鼠随机分为安静对照组(Con组),白藜芦醇组(Rsv组),力竭运动组(Ex组),力竭运动+白藜芦醇组(Ex+Rsv组)。Rsv和Ex+Rsv组每天灌胃50 mg/kg体重剂量的白藜芦醇, Ex和Ex+Rsv组进行4周力竭训练,最后1次训练后24 h取材。本研究结果显示,与Con组相比,Ex组大鼠Scr(175.66±16.08 vs.153.34±8.67,P<0.01)、BUN(6.67±0.53 vs.5.37±0.19,P<0.01)和尿NGAL(9.01±0.18 vs.7.48±0.31,P<0.01)水平均显著升高,Ex组大鼠肾组织NF-κB P65在蛋白质水平表达显著升高(0.77±0.10 vs. 0.27±0.03,P<0.01);各组大鼠肾组织SIRT1在蛋白质水平表达上,Rsv组显著高于Con组(0.90±0.14 vs. 0.43±0.15,P<0.05),Ex+Rsv组显著高于Ex组(1.0±0.28 vs. 0.38±0.12,P<0.01);与Ex组相比,Ex+Rsv组大鼠肾组织NF-κB P65(0.57±0.13 vs. 0.77±0.10,P<0.05)和Ac-NF-κB P65(0.52±0.13 vs. 0.78±0.11,P<0.05)在蛋白质水平表达显著降低。以上结果表明,4周大强度力竭运动导致大鼠出现运动性肾损伤,并激活大鼠肾NF-κB的表达。白藜芦醇可显著提高大鼠肾组织SIRT1在蛋白质水平的表达,并增加脱乙酰化作用,降低NF-κB P65蛋白质乙酰化修饰水平,进一步降低NF-κB的表达。白藜芦醇减轻力竭训练致大鼠肾的炎症反应的机制可能与SIRT1/NF-κB通路有关。

Resveratrol is a naturally sirtuin1 activator, its renal protective effects have been validated in a variety of animal models of kidney disease. However, there is still no systematic study on the effects of resveratrol in rat kidney damage caused by exhaustive training, and its signaling regulation of renal inflammatory response. In this study, 32 SD rats were randomly divided into: control group(Con), resveratrol group(Rsv), exhaustive exercise group(Ex), and exhaustive exercise + resveratrol group(Ex+Rsv). Rsv and Ex+Rsv groups were given resveratrol(50 mg/kg body weight) by gavage. Ex and Ex+Rsv groups were subjected to exhaustive training for 4 weeks. Anesthesia was applied at 24 hours after the last training. The results showed that Scr(175.66 ± 16.08 vs. 153.34 ± 8.67, P < 0.01), BUN(6.67 ± 0.53 vs. 5.37 ± 0.19, P < 0.01) and urinary NGAL(9.01 ± 0.18 vs. 7.48 ± 0.31, P < 0.01) in the Ex group were significantly increased as compared with the Con group. Furthermore, the expression of NF-κB P65(0.77 ± 0.10 vs. 0.27 ± 0.03, P< 0.01) was also significantly increased in Ex group;the expression of SIRT1 in Rsv group was significantly higher than that in Con group(0.90 ± 0.14 vs. 0.43 ± 0.15, P< 0.05), Ex+Rsv group was significantly higher than Ex group(1.0 ± 0.28 vs. 0.38 ± 0.12, P < 0.01);Compared with the Ex group, the NF-κB P65(0.57 ± 0.13 vs. 0.77 ± 0.10, P < 0.05) and Ac-NF-κB P65(0.52 ± 0.13 vs. 0.78 ± 0.11, P< 0.05) in Ex+Rsv showed a significant decrease in protein level. The above results indicate that high-intensity exhaustive exercise leads to renal injury in rats and activates the expression of NF-κB in rat kidney. Resveratrol can significantly increase the expression of SIRT1 at the protein level and increase the deacetylation to reduce the level of acetylation of NF-κB P65 protein, further reducing the expression of NF-κB. The mechanism by which resveratrol reduces the inflammatory response induced by exhaustive training in rats may be related to the SIRT1/NF-κB pathway.