Yang Kang, Li Wei-Fang, Yu Jun-Feng, Yi Cheng, Huang Wei-Feng
Department of Urology, The First People's Hospital Of Yichang, China Three Gorges University, Yichang, Hubei, China; Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, Hubei, China.
Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, Hubei, China.
J Surg Res. 2017 Jun 15;214:69-78. doi: 10.1016/j.jss.2017.02.067. Epub 2017 Mar 6.
Renal ischemia/reperfusion (I/R)-induced acute kidney injury remains to be a troublesome condition in clinical practice. Although the exact molecular mechanisms underlying renal I/R injury are incompletely understood, the deleterious progress of renal I/R injury involves inflammation, apoptosis, and oxidative stress. Diosmetin is a member of the flavonoid glycosides family, which suppresses the inflammatory response and cellular apoptosis and enhances antioxidant activity. The purpose of this study was to investigate the protective effect of diosmetin on I/R-induced renal injury in mice.
Thirty BALB/c mice were randomly divided into five groups. Four groups of mice received diosmetin (0.25, 0.5, and 1 mg/kg) or vehicle (I/R group) before ischemia. Another group received vehicle without ischemia to serve as a negative control (sham-operated group). Twenty-four hours after reperfusion, serum and renal tissues were harvested to evaluate renal function and histopathologic features. In addition, the expression of inflammation-related proteins, apoptotic molecules, and antioxidant enzymes was analyzed.
Compared with sham mice, the I/R group significantly exacerbated renal function and renal tube architecture and increased the inflammatory response and renal tubule apoptosis. Nevertheless, pretreatment with diosmetin reversed these changes. In addition, diosmetin treatment resulted in a marked increase in antioxidant protein expression compared with I/R mice.
The renoprotective effects of diosmetin involved suppression of the nuclear factor-κB and mitochondrial apoptosis pathways, as well as activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. Diosmetin has significant potential as a therapeutic intervention to ameliorate renal injury after renal I/R.
肾缺血/再灌注（I/R）诱导的急性肾损伤在临床实践中仍然是一个棘手的问题。尽管肾I/R损伤的确切分子机制尚未完全明确，但肾I/R损伤的有害进展涉及炎症、凋亡和氧化应激。香叶木素是黄酮苷类家族的成员，可抑制炎症反应和细胞凋亡，并增强抗氧化活性。本研究的目的是探讨香叶木素对小鼠I/R诱导的肾损伤的保护作用。
30只BALB/c小鼠随机分为五组。四组小鼠在缺血前接受香叶木素（0.25、0.5和1mg/kg）或溶剂（I/R组）。另一组接受无缺血的溶剂作为阴性对照（假手术组）。再灌注24小时后，收集血清和肾组织以评估肾功能和组织病理学特征。此外，分析炎症相关蛋白、凋亡分子和抗氧化酶的表达。
与假手术小鼠相比，I/R组显著加重了肾功能和肾小管结构损伤，并增加了炎症反应和肾小管凋亡。然而，香叶木素预处理可逆转这些变化。此外，与I/R小鼠相比，香叶木素治疗导致抗氧化蛋白表达显著增加。
香叶木素的肾脏保护作用涉及抑制核因子κB和线粒体凋亡途径，以及激活核因子红细胞2相关因子2/血红素加氧酶-1途径。香叶木素作为一种治疗干预措施，在改善肾I/R后的肾损伤方面具有巨大潜力。
