OBJECTIVES:This study aims to determine the effects of ozone therapy on restoring impaired Nrf2 activation to ameliorate chronic tubulointerstitial injury in rats with adenine-induced CKD. MATERIALS AND METHODS:Sprague-Dawley rats were fed with 0.75% adenine-containing diet to induce CKD and chronic tubulointerstitial injury. Ozone therapy was administered by rectal insufflation. After 4 weeks, serum and kidney samples were collected and analyzed. Renal function and systemic electrolyte level were detected. Pathological changes in kidney were assessed by hematoxylin-eosin staining and Masson trichrome staining. Nrf2 activation was detected by immunohistochemistry and Western blot analyses. The levels of SOD, CAT, GSH, PCO, and MDA were detected in the kidney. Immunohistochemistry, Western blot, and real-time PCR analyses were performed to evaluate the activation of the nuclear factor kappa B (NF-κB) P65 pathway and inflammation infiltration in the tubulointerstitium of the rats. RESULTS:Ozone therapy improved severe renal insufficiency and tubulointerstitial morphology injury as well as restored Nrf2 activation and inhibited the NF-κB pathway in rats with adenine-induced CKD. Ozone therapy also up-regulated anti-oxidation enzymes (SOD, CAT, and GSH) and down-regulated oxidation products (PCO and MDA), as well as inflammatory cytokines (IL-1β, IL-6, TNF-α, and ICAM-1) in the kidney. CONCLUSION:These findings indicated that ozone therapy could attenuate tubulointerstitial injury in rats with adenine-induced CKD by mediating Nrf2 and NF-κB.

译文

目的:本研究旨在确定臭氧治疗对恢复腺嘌呤诱发的CKD大鼠慢性肾小管间质损伤的Nrf2活化受损的影响。
材料与方法:给Sprague-Dawley大鼠喂食含0.75%腺嘌呤的饮食,以诱导CKD和慢性肾小管间质损伤。臭氧通过直肠吹入法进行治疗。 4周后,收集并分析血清和肾脏样品。检测肾功能和全身电解质水平。通过苏木精-伊红染色和Masson三色染色评估肾脏的病理变化。通过免疫组织化学和蛋白质印迹分析检测到Nrf2激活。在肾脏中检测到了SOD,CAT,GSH,PCO和MDA的水平。进行了免疫组织化学,蛋白质印迹和实时PCR分析,以评估大鼠肾小管间质中核因子κB(NF-κB)P65途径的激活和炎症浸润。
结果:臭氧治疗改善了腺嘌呤诱发的CKD大鼠的严重肾功能不全和肾小管间质形态损伤,并恢复了Nrf2活化并抑制了NF-κB通路。臭氧疗法还可以上调抗氧化酶(SOD,CAT和GSH)和下调氧化产物(PCO和MDA),以及炎性细胞因子(IL-1β,IL-6,TNF-α和ICAM) -1)在肾脏。
结论:这些发现表明,臭氧治疗可以通过介导Nrf2和NF-κB减轻腺嘌呤诱发的CKD大鼠肾小管间质损伤。

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