Department of Biomedical Sciences, Pharmacology Division, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
Pharmacology. 2010;85(3):158-67. doi: 10.1159/000269779. Epub 2010 Feb 11.
We investigated the protective effect of telmisartan, an angiotensin II receptor antagonist, against ischemia/reperfusion renal injury in rats. Bilateral ischemia was induced by clamping both renal vascular pedicles for 45 min followed by reperfusion for 3 h. Untreated rats exposed to ischemia/reperfusion showed significant elevations in blood urea nitrogen and serum creatinine levels, renal tissue levels of malondialdehyde, tumor necrosis factor-alpha and nitric oxide, and caspase-3 activity. This was associated with significant decreases in renal reduced glutathione level, catalase and superoxide dismutase activities. Also, significant increases in serum and renal tissue levels of homocysteine were detected following ischemia/reperfusion. Pre-ischemic treatment with telmisartan (0.3 mg/kg/day, i.p.) for 7 consecutive days significantly attenuated the increases in blood urea nitrogen, serum creatinine, renal malondialdehyde, tumor necrosis factor-alpha, nitric oxide, caspase-3 activity, and serum and renal homocysteine levels, and significantly restored the renal antioxidant defenses. In addition, light and electron microscopic examinations revealed that telmisartan pre-treatment markedly ameliorated ischemia/reperfusion-induced renal tissue damage. It was concluded that telmisartan, through its antioxidant, anti-inflammatory and antiapoptotic effects, can be considered a potential candidate to protect against acute ischemia/reperfusion renal injury.
我们研究了血管紧张素 II 受体拮抗剂替米沙坦对大鼠肾缺血/再灌注损伤的保护作用。通过夹闭双侧肾血管蒂 45 分钟诱导双侧缺血，然后再灌注 3 小时。未接受治疗的缺血/再灌注大鼠的血尿素氮和血清肌酐水平、肾组织丙二醛、肿瘤坏死因子-α和一氧化氮水平以及半胱氨酸天冬氨酸蛋白酶-3 活性显著升高。这与肾还原型谷胱甘肽水平、过氧化氢酶和超氧化物歧化酶活性显著降低有关。此外，缺血/再灌注后还检测到血清和肾组织中同型半胱氨酸水平显著升高。缺血前用替米沙坦（0.3mg/kg/天，腹腔注射）连续 7 天预处理可显著减轻血尿素氮、血清肌酐、肾丙二醛、肿瘤坏死因子-α、一氧化氮、半胱氨酸天冬氨酸蛋白酶-3 活性和血清及肾同型半胱氨酸水平的升高，并显著恢复肾抗氧化防御能力。此外，光镜和电镜检查显示，替米沙坦预处理可显著改善缺血/再灌注引起的肾组织损伤。结论：替米沙坦通过抗氧化、抗炎和抗细胞凋亡作用，可被视为预防急性肾缺血/再灌注损伤的潜在候选药物。
