Ozgen Zeynep Erdogmus, Erdinc Meral, Kaya Meryem Seyda, Aktar Fesih, Ozekinci Selver Ozsener, Erdinc Levent, Uyar Emre
Department of Pharmacology, School of Pharmacy, Dicle University, Diyarbakir, Turkey.
Department of Pharmacology, School of Medicine, Dicle University, Diyarbakir, Turkey.
J Mol Histol. 2024 Dec 4;56(1):30. doi: 10.1007/s10735-024-10281-7.
We aimed to investigate the protective effects of low dose cyclosporin A (CsA) on ischemia-reperfusion (IR) injury in rat the kidney and on the apoptotic and necroptotic mechanisms involved. 1. Control group (received a single intraperitoneal (i.p.) dose of 1 ml sterile saline 15 min before the surgical procedure), 2. IR group (was subjected to 30 min of bilateral kidney ischemia followed by 90 min of reperfusion; and received a single i.p. dose of 1 ml sterile saline 15 min before the IR procedure, 3. IR + CsA group (received a single i.p. dose of 3 mg/kg CsA 15 min before the IR procedure. Renal functions (renal perfusion pressures, and serum urea-creatinine levels), kidney histological scores, MDA levels, and TNF-α, caspase-3, RIP1, RIP3, MLKL, CaMKII and CypD protein expressions were also measured. Renal perfusion pressures (PP), serum urea and creatinine levels, renal tissue MDA levels, and the protein expression levels of TNF-α, caspase-3, RIP1, RIP3, MLKL, CAMKII and CypD were significantly increased in the IR group compared to the control group (p < 0.05), Additionally, there were significant decreases in all the parameters in the IR + CsA group compared to those in the IR group (p < 0.05). Furthermore, histopathological analyses revealed significantly higher kidney injury scores in the IR group compared to the control group, and low dose CsA treatment improved the injury. A single low dose of CsA injection 15 min before IR, demonstrated a protective effect on bilateral renal IR injury and a reduction in apoptotic and necroptopic markers which is resulted in improvement of renal functions.
我们旨在研究低剂量环孢素A（CsA）对大鼠肾脏缺血再灌注（IR）损伤的保护作用以及相关的凋亡和坏死性凋亡机制。1. 对照组（在手术前15分钟腹腔内注射1毫升无菌生理盐水），2. IR组（双侧肾脏缺血30分钟，随后再灌注90分钟；在IR手术前15分钟腹腔内注射1毫升无菌生理盐水），3. IR + CsA组（在IR手术前15分钟腹腔内注射3毫克/千克CsA）。还测量了肾功能（肾灌注压和血清尿素 - 肌酐水平）、肾脏组织学评分、丙二醛（MDA）水平以及肿瘤坏死因子 - α（TNF - α）、半胱天冬酶 - 3（caspase - 3）、受体相互作用蛋白1（RIP1）、受体相互作用蛋白3（RIP3）、混合谱系激酶结构域样蛋白（MLKL）、钙调蛋白依赖性蛋白激酶II（CaMKII）和亲环蛋白D（CypD）的蛋白表达。与对照组相比，IR组的肾灌注压（PP）、血清尿素和肌酐水平、肾组织MDA水平以及TNF - α、caspase - 3、RIP1、RIP3、MLKL、CaMKII和CypD的蛋白表达水平显著升高（p < 0.05）。此外，与IR组相比，IR + CsA组的所有参数均显著降低（p < 0.05）。此外，组织病理学分析显示，与对照组相比，IR组的肾脏损伤评分显著更高，低剂量CsA治疗改善了损伤。在IR前15分钟单次注射低剂量CsA，对双侧肾脏IR损伤具有保护作用，并降低了凋亡和坏死性凋亡标志物，从而改善了肾功能。
