Relaxin protects against renal ischemia-reperfusion injury.
Relaxin, a pregnancy hormone, has antiapoptotic and anti-inflammatory properties. The aim of this study was to determine the effects of relaxin on ischemia-reperfusion (IR)-induced acute kidney injury. Male rats underwent unilateral nephrectomy and contralateral renal IR (45 min of renal pedicle clamping). Rats were divided into three groups: 1) sham group, 2) IR group, and 3) IR-RLX group (rats treated with relaxin before ischemia). In this group, relaxin was infused at 500 ng/h via subcutaneous osmotic minipump for 24 h beginning 2 h before renal ischemia. At 24 h after reperfusion, renal function was assessed and kidneys were removed for analysis. There was no significant difference in blood pressure among the three groups. IR increased plasma levels of creatinine and urea nitrogen, and relaxin provided protection against the increases in these two parameters. Relaxin significantly decreased plasma TNF-α levels and renal TNF receptor 1 mRNA expression, compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in IR rats compared with the IR-RLX rats. RLX significantly reduced apoptotic cell counts compared with the IR group. Overexpression of caspase-3 observed in the IR kidneys was reduced in the IR-RLX group. The results demonstrated that relaxin provided protection against IR-induced renal injury by reducing apoptosis and inflammation.
Dept. of Medicine, Yaizu Municipal General Hospital, 1000, Dohbara, Yaizu, Shizuoka, 425-8505, Japan. ni100330@cy.tnc.ne.jp.
Takuya
T
Yoshida
Hiromichi
H
Kumagai
Tetsuya
T
Kohsaka
Naoki
N
Ikegaya
D058186:Acute Kidney Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D011897:Random Allocation; D051381:Rats; D012065:Relaxin / Q000494:pharmacology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D034421:Sus scrofa; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D014409:Tumor Necrosis Factor-alpha; D012065:Relaxin
apoptosis; caspase-3; relaxin