Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China.
Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China.
J Surg Res. 2014 Mar;187(1):289-96. doi: 10.1016/j.jss.2013.10.008. Epub 2013 Oct 10.
Ischemia-reperfusion injury (IRI) has been considered as the major cause of acute kidney injury and can result in poor long-term graft function. Functional recovery after IRI is impaired in the elderly. In the present study, we aimed to compare kidney morphology, function, oxidative stress, inflammation, and development of renal fibrosis in young and aged rats after renal IRI.
Rat models of warm renal IRI were established by clamping left pedicles for 45 min after right nephrectomy, then the clamp was removed, and kidneys were reperfused for up to 12 wk. Biochemical and histologic renal damage were assessed at 12 wk after reperfusion. The immunohistochemical staining of monocyte macrophage antigen-1 (ED-1) and transforming growth factor beta 1 (TGF-β1) and messenger RNA level of TGF-β1 in the kidney were analyzed.
Renal IRI caused significant increases of malondialdehyde and 8-hydroxydeoxyguanosine levels and a decrease of superoxide dismutase activity in young and aged IRI rats; however, these changes were more obvious in the aged rats. IRI resulted in severe inflammation and tubulointerstitial fibrosis with decreased creatinine (Cr) clearance and increased histologic damage in aged rats compared with young rats. Moreover, we measured the ratio of Cr clearance between young and aged IRI rats. It demonstrated that aged IRI rats did have poor Cr clearance compared with the young IRI rats. ED-1 and TGF-β1 expression levels in the kidney were significantly higher in aged rats than in young rats after IRI.
Aged rats are more susceptible to IRI-induced renal failure, which may associate with the increased oxidative stress, increased histologic damage, and increased inflammation and tubulointerstitial fibrosis. Targeting oxidative stress and inflammatory response should improve the kidney recovery after IRI.
缺血再灌注损伤（IRI）被认为是急性肾损伤的主要原因，并可能导致移植肾功能不良。老年人的 IRI 后功能恢复受损。在本研究中，我们旨在比较年轻和老年大鼠肾 IRI 后肾脏形态、功能、氧化应激、炎症和肾纤维化发展的差异。
通过右肾切除后夹闭左侧蒂 45 分钟建立大鼠温热肾 IRI 模型，然后去除夹闭，肾脏再灌注长达 12 周。再灌注后 12 周评估生化和组织学肾损伤。分析单核巨噬细胞抗原-1（ED-1）和转化生长因子β 1（TGF-β1）的免疫组织化学染色和肾脏中 TGF-β1 的信使 RNA 水平。
肾 IRI 导致年轻和老年 IRI 大鼠丙二醛和 8-羟基脱氧鸟苷水平升高，超氧化物歧化酶活性降低；但老年大鼠的这些变化更为明显。与年轻大鼠相比，IRI 导致老年大鼠炎症和肾小管间质纤维化更严重，肌酐（Cr）清除率降低，组织学损伤增加。此外，我们测量了年轻和老年 IRI 大鼠之间的 Cr 清除率比值。结果表明，与年轻 IRI 大鼠相比，老年 IRI 大鼠的 Cr 清除率确实较差。IRI 后老年大鼠肾脏中 ED-1 和 TGF-β1 的表达水平明显高于年轻大鼠。
老年大鼠对 IRI 引起的肾衰竭更为敏感，这可能与氧化应激增加、组织学损伤增加、炎症和肾小管间质纤维化增加有关。针对氧化应激和炎症反应可能会改善 IRI 后的肾脏恢复。
