缺血后处理对缺血-再灌注大鼠肾脏转录因子Nrf2表达的影响

Effect of ischemic postprocessing on the expression of transcription factor Nrf2 in the kidney of rats with ischemia reperfusion injury

目的:研究缺血后处理对缺血-再灌注大鼠肾脏转录因子红细胞系-2相关因子2(Nrf2)表达的影响,探讨Nrf2在缺血-再灌注中的作用及其意义。方法:SD大鼠30只分三组:假手术C组、缺血-再灌注(I-R)组、缺血后处理(IPO)组。于再灌注2h处死大鼠,取血检测血清肌酐(Cr)、尿素氮(BUN)及胱抑素C(Cys C)的水平,并测定血清超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。应用RT-PCR及Western-blot方法定量分析Nrf2,血红素氧合酶1(H0-1),y-谷氨酞半肤氨酸合成酶(-GCS)蛋白在肾组织中的表达。结果:IPO组肾组织Cr,BUN,Cys C及MDA水平显著低于缺血再灌注组,SOD活性显著高于缺血再灌注组,Nrf2,H0-1,γ-GCS蛋白在肾组织中的表达明显增多。结论:缺血后处理可能通过提高Nrf2在肾组织中的表达增多避免加重肾缺血再灌注损伤。

Objective To investigate the expression of Nrf2 on acute renal injury induced by IR and on the effectiveness of the IPO. Therefore,to elucidate the role of Nrf2. Method 30 SD male rats were divided randomly into three groups： sham operation group（ group C,n = 10）,ischemia- reperfusion group（ group I / R,n = 10）,ischemic postconditioning（ group IPO,n = 10）. ischemia- reperfusion model of renal and ischemic postconditioning model were used,BUN Cr and Cys C content in serum were also examined,and the levels of SOD,MDA in renal tissue were measured,the protein expression of Nrf2,γ- GCS and HO- 1 in renal tissue were detectedd by immunohistochemical and Western blotting technique. Results The degree of renal injury in group I / R was increased after 60 min of ischemia and 2 hours of reperfusion（ P〈0. 05） as well as of BUN,Cr and NAGL（ P〈0. 05）. The expression of Nrf2 HO- 1 and γ- GCS in group I / R was significantly higher than those in group C by immunohistochemical technology and Western blotting analysis（ P〈0. 05）. The level of MDA in group IR were significantly higher than that in group C in renal tissue（ P〈0. 05）,while the activity of SOD enzyme was significantly lower than that in group C（ P〈0. 05）. After ischemic postconditoning treatment,the degree of renal injury in group IPO was higher than that in group C（ P〈0. 05）,but lower than that in group IR（ P〈0. 05）,the serum BUN,Cr and Cys C were significantly reduced in group IPO（ P〈0. 05）. The expression of Nrf2 γ- GCS and HO- 1 in group IPO were significantly increased than those in group IR and group C by immunohistochemical and Western blotting analysis（ P〈0. 05）,the level of MDA in group IPO was significantly reduced than that in group IR（ P〈0. 05）,but higher than that in group C（ P〈0. 05）,the activity of SOD was significantly higher in group IPO than that in group IR（ P〈0. 05）,but lower than that in group C（ P〈0. 05）. Conclusion IPO intervention by improving the expression of Nrf2 in renal tissue can reduce the renal injury caused by isehemia- reperfusion.