Role of SIRT1/Klotho signaling pathway in renal injury induced by myocardial ischemia-reperfusion in diabetic rats
10.3760/cma.j.cn131073-20240805-00416
- VernacularTitle:SIRT1/Klotho信号通路在糖尿病大鼠心肌缺血再灌注诱发肾损伤中的作用
- Author:
Jiahui CUI
1
;
Zhen QIU
1
;
Zhongyuan XIA
1
Author Information
1. 武汉大学人民医院麻醉科，武汉 430060
- Publication Type:Journal Article
- Keywords:
Sirtuin 1;
Klotho proteins;
Diabetes mellitus;
Myocardial reperfusion injury;
Acute kidney injury
- From:
Chinese Journal of Anesthesiology
2025;45(4):469-473
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of silent information regulator factor 2-related enzyme 1 (SIRT1)/Klotho signaling pathway in renal injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods:Forty SPF healthy male rats, aged 6-8 weeks, weighing 140-170 g, were divided into 5 groups ( n=8 each) by the random number table method: non-diabetic sham operation group (NS group), non-diabetic I/R group (NIR group), diabetic sham operation group (DS group), diabetic I/R group (DIR group), and diabetic I/R + SIRT1 inhibitor EX-527 group (DIR+ EX-527 group). Diabetes mellitus was induced by intraperitoneal streptozotocin 60 mg/kg. The myocardial I/R was produced by temporary ligation of the left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion. EX-527 5 mg/kg was intraperitoneally injected before ischemia and at 10 min before reperfusion in DIR+ EX-527 group. Serum levels of lactic dehydrogenase (LDH), cardiac troponin I (cTnI), malondialdehyde (MDA), superoxide dismutase (SOD), blood urea nitrogen (BUN) and creatinine (Cr) were determined at the end of reperfusion. Renal tissues were collected for observation of the pathological changes and for detection of the expression of SIRT1, Klotho, and interleukin-1 β (IL-1β) by Western blot. Results:Compared with NS group, the serum levels of LDH, cTnI, BUN and MDA were significantly increased, the serum levels of SOD were decreased, the expression of Klotho and SIRT1 was down-regulated, the expression of IL-1β was up-regulated ( P<0.05), and the pathological damage to renal tissues was marked in NIR group and DS group. Compared with DS group and NIR group, the serum levels of LDH, cTnI, BUN, Cr and MDA were significantly increased, the serum levels of SOD were decreased, the expression of Klotho and SIRT1 was down-regulated, the expression of IL-1β was up-regulated ( P<0.01), and the pathological damage to renal tissues was aggravated in DIR gruop. Compared with DIR gruop, the serum levels of LDH, cTnI, BUN, Cr and MDA were significantly increased, the level of serum SOD was decreased, the expression of Klotho and SIRT1 was down-regulated, the expression of IL-1β was up-regulated ( P<0.01), and the pathological damage to renal tissues was aggravated in DIR+ EX-527 group. Conclusions:Weakened activation of SIRT1/Klotho signaling pathway may be involved in the mechanism of myocardial I/R-induced renal injury in diabetic rats.
