Chen Zhiyuan, Liu Xiuheng, Yu Gang, Chen Hui, Wang Lei, Wang Zhishun, Qiu Tao, Weng Xiaodong
a Department of Urology , Renmin Hospital of Wuhan University , Wuhan, Hubei Province , P.R. China.
Ren Fail. 2016 Jun;38(5):822-30. doi: 10.3109/0886022X.2016.1143757. Epub 2016 Feb 24.
Tubulointerstitium inflammation is a common pathway aggravating chronic kidney disease (CKD) progression and the mechanism is partly associated with excessive activation of toll-like receptor 4 (TLR4) in tubulointerstitium. Ozone therapy is demonstrated to alleviate inflammation in some experiments. The aim of this study is to examine whether ozone therapy could ameliorate chronic tubulointerstitium inflammation by suppressing TLR4 in adenine-induced CKD rats. Sprague-Dawley rats were fed with 0.75% adenine-containing diet to induce CKD and tubulointerstitium inflammation injury. Ozone therapy (1.1 mg/kg) was simultaneously administrated by rectal insufflations (i.r.). After 4 weeks, serum and kidney samples were collected for detection. Renal function and systemic electrolyte were detected. Renal pathological changes were assessed by hematoxylin-eosin (H&E) staining and Masson trichrome (MT) staining. Immunohistochemistry, Western blot and Real-time PCR were applied to evaluate tubulointerstitium inflammation as well as the expression of TLR4 and phosphorylated nuclear factor kappa B P65 (p-NF-κB P65) in rats. The results showed ozone therapy improved serious renal insufficiency, systemic electrolyte disorder and tubulointerstitium morphology damages in adenine-induced CKD rats. In addition, ozone therapy suppressed excessive activation of TLR4 and p-NF-κB P65 in the tubulointerstitium of adenine-induced CKD rats, accompanied by the reduction of inflammation-related cytokines including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). The protein expression of TLR4 was positively correlated with the protein expression levels of MCP-1 (r = 0.7863, p < 0.01) and TNF-α (r = 0.7547, p < 0.01) in CKD rats. These findings indicated ozone therapy could attenuate tubulointerstitium inflammation injury in adenine-induced CKD rats and the mechanism might associate with the mediation of TLR4.
肾小管间质炎症是加重慢性肾脏病（CKD）进展的常见途径，其机制部分与肾小管间质中Toll样受体4（TLR4）的过度激活有关。在一些实验中，臭氧疗法被证明可减轻炎症。本研究的目的是探讨臭氧疗法是否能通过抑制腺嘌呤诱导的CKD大鼠中的TLR4来改善慢性肾小管间质炎症。将Sprague-Dawley大鼠喂以含0.75%腺嘌呤的饮食以诱导CKD和肾小管间质炎症损伤。通过直肠注入（i.r.）同时给予臭氧疗法（1.1mg/kg）。4周后，收集血清和肾脏样本进行检测。检测肾功能和全身电解质。通过苏木精-伊红（H&E）染色和Masson三色（MT）染色评估肾脏病理变化。应用免疫组织化学、蛋白质印迹法和实时定量PCR评估大鼠肾小管间质炎症以及TLR4和磷酸化核因子κB P65（p-NF-κB P65）的表达。结果显示，臭氧疗法改善了腺嘌呤诱导的CKD大鼠严重的肾功能不全、全身电解质紊乱和肾小管间质形态损伤。此外，臭氧疗法抑制了腺嘌呤诱导的CKD大鼠肾小管间质中TLR4和p-NF-κB P65的过度激活，同时炎症相关细胞因子包括单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）减少。在CKD大鼠中，TLR4的蛋白表达与MCP-1（r = 0.7863，p < 0.01）和TNF-α（r = 0.7547，p < 0.01）的蛋白表达水平呈正相关。这些发现表明，臭氧疗法可减轻腺嘌呤诱导的CKD大鼠的肾小管间质炎症损伤，其机制可能与TLR4的介导作用有关。
Zotero 插件