肾小管上皮细胞线粒体氧化损伤在肾间质纤维化中的作用及机制

Effect and mechanism of mitochondria oxidative damage in renal tubular epithelial cells on renal interstitial fibrosis

目的探讨肾小管上皮细胞线粒体氧化损伤在肾间质纤维化中的作用机制。方法2015年6～12月期间，于本地动物实验中心选取60只健康雄性大鼠，根据处理方法的不同将其分为实验组和对照组，其中实验组行左侧输尿管结扎术．对照组则仅接受左侧输尿管游离，14d后对两组大鼠的左侧肾脏中线粒体相关基因的表达情况、肾脏功能等参数进行检测分析。结果实验组大鼠术后14dmtDNA（1．49±0．12）、NRF1（1．87±0．17）、PGC1a（1．76±0．21）、Drp1（2．49±0．24）、Mfn2（2．45±0．27）的表达水平均明显高于对照组（1．07±0.23、1．11±0．29、1．05±0．32、1．14±0．35．1．17±0．14），差异具有统计学意义（P〈0．05）；术后14d，实验组大鼠肾脏组织中的cox（2．61±0．27）明显高于对照组的（1．07±0．19），SOD较对照组明显降低（0．55±0．16 vs 1．07±0．18），其RIF指数（22．76±1．39）明显高于对照组的（0．81±0．16），差异具有统计学意义（P〈0．05）。结论在肾间质纤维化中肾小管上皮细胞线粒体氧化损伤发挥着十分重要的作用，缺氧所造成的线粒体氧化损伤会造成肾小管功能受损，引起大量致纤维因子的产生，并从多途径引起肾间质纤维化。

Objective To discuss the effect and mechanism of mitochondria oxidative damage in renal tubular epithelial cells on renal interstitial fibrosis. Methods A total of 60 health male rats were selected from a local animal experimental center from June to December 2015 and divided into study group and control group. Rats in the study group were given left ureteral obstruction, while those in the control group were only given left ureteral mobilization. Parameters in- cluding the expression of genes in mitochondria and renal function of the left kidney were detected and analyzed after 14 days. Results At 14 d after surgery, the expression levels of mtDNA （1.49±0.12）, regenerating gene （1.87±0.17）, interrupted gene（1.76±0.21）, and fusion gene（2.49±0.24, 2.45±0.27） in the study group were all significantly higher than those （1.07±0.23, 1.11±0.29, 1.05±0.32, 1.14±0.35, and 1.17±0.14） in the control group （P〈0.05）. The level of COX （2.61±0.27） in kidney tissues in the study group was significantly higher than that （1.07±0.19） in the control group, while the level of SOD was significantly lower than the control group（0.55±0.16 vs 1.07±0.18）. The RIF index （22.76± 1.39） in the study group was significantly higher than that （0.81±0.16） in the control group （P〈0.05）. Conclusion Mitochondria oxidative damage in renal tubular epithelial cells has a significant effect on renal interstitial fibrosis. Mitochondria oxidative damage caused by anoxia may lead to functional impairment of kidney tubules, inducing a large number of fibrosis factors and resulting in renal interstitial fibrosis from multiple pathways.