Xie Da, Xu Yong, Jing Wang, Juxiang Zeng, Hailun Li, Yu Hu, Zheng Dong-Hui, Lin Yong-Tao
Department of Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Nephrology, Huai'an Hospital Affiliated to Xuzhou Medical University and Huai'an Second Hospital, Huai'an, China.
Oncotarget. 2017 Apr 11;8(15):24154-24162. doi: 10.18632/oncotarget.16530.
Renal ischemia-reperfusion (I/R) injury is one of the most common causes of acute renal failure, the prognosis of which remains poor and there still lacks of effective therapeutics available in the clinic. This study aimed at investigating the effects of Berberine nanoparticles (BBR-NP) on the ischemia-reperfusion injury of renal tubular epithelial cells and underlying the mechanisms. Our results showed that in a rat model of renal I/R injury, BBR and BBR-NP protected renal against injury both functionally (as assessed by serum urea nitrogen and creatinine level) and morphologically (as assessed by HE staining, transmission electron microscopy and TUNEL staining) in a dose-dependent manner, with the effects of BBR-NP superior to BBR alone. Mechanism investigation showed that BBR-NP reversed oxidative stress and subsequent apoptosis of renal cells, as demonstrated by the decreased expression of proteins involved in the oxidative stress and mitochondrial stress pathways. In conclusion, our study showed that BBR-NP is superior to BBR alone in protecting renal against I/R injury and explored the underlying mechanisms, which should be tested in further studies and might give impetus to the development of novel therapeutics based on BBR-NP against renal I/R.
肾缺血再灌注（I/R）损伤是急性肾衰竭最常见的病因之一，其预后仍然很差，临床上仍缺乏有效的治疗方法。本研究旨在探讨黄连素纳米颗粒（BBR-NP）对肾小管上皮细胞缺血再灌注损伤的影响及其潜在机制。我们的结果表明，在大鼠肾I/R损伤模型中，BBR和BBR-NP在功能上（通过血清尿素氮和肌酐水平评估）和形态学上（通过HE染色、透射电子显微镜和TUNEL染色评估）均以剂量依赖的方式保护肾脏免受损伤，且BBR-NP的效果优于单独使用BBR。机制研究表明，BBR-NP可逆转肾细胞的氧化应激及随后的凋亡，这可通过氧化应激和线粒体应激途径相关蛋白表达的降低得以证明。总之，我们的研究表明，BBR-NP在保护肾脏免受I/R损伤方面优于单独使用BBR，并探索了其潜在机制，这应在进一步研究中进行验证，可能会推动基于BBR-NP的新型治疗药物针对肾I/R的开发。
