Aging aggravates long-term renal ischemia-reperfusion injury in a rat model.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China.
Xianlin
X
Xu
Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China.
Min
M
Fan
Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China. Electronic address: xuxianlin2013@126.com.
Xiaozhou
X
He
Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China.
Jipu
J
Liu
Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China.
Jiandi
J
Qin
Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou, China.
Jianan
J
Ye
D000080242:8-Hydroxy-2'-Deoxyguanosine; D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D012720:Severity of Illness Index; D013995:Time
D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
8-Hydroxydeoxyguanosine; Aged rats; Ischemia/reperfusion; Malondialdehyde; Oxidative stress; Reactive oxygen species; Transforming growth factor beta 1