右美托咪定对小鼠心肌缺血再灌注引发肾损伤的影响  

Influence of dexmedetomidine on renal injury induced by myocardial ischemia-reperfusion in mice

作　　者：于文彬 程虎[1] 朱阔 任炳楠 吴建江[1] YU Wenbin;CHENG Hu;ZHU Kuo;REN Bingnan;WU Jianjiang(Department of Anesthesiology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang Uygur Autonomous Region 830054,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,新疆维吾尔自治区乌鲁木齐830054

出　　处：《中华实用诊断与治疗杂志》2025年第2期105-111,共7页Journal of Chinese Practical Diagnosis and Therapy

基　　金：国家自然科学基金(82060056)。

摘　　要：目的 构建小鼠心肌缺血再灌注(IR)诱发肾损伤模型,观察小鼠肾组织低氧诱导因子-1α(HIF-1α)表达,探讨右美托咪定对小鼠心肌IR引发肾损伤的影响及可能机制。方法 健康雄性C57BL/6小鼠50只,体质量20~30 g,随机分为假手术组、IR组、IR+右美托咪定组(IRD组)、IR+HIF-1α抑制剂组(IR-M组)、IR+右美托咪定+HIF-1α抑制剂组(IRD-M组)各10只,IR组、IRD组、IR-M组、IRD-M组采用结扎左冠状动脉前降支(LAD)30 min、再灌注120 min的方法制备小鼠心肌IR引发肾损伤模型;假手术组LAD仅穿线,不结扎。IRD组、IRD-M组LAD结扎前30 min腹腔注射右美托咪定25μg/kg;IR-M组、IRD-M组LAD结扎前5 min腹腔注射HIF-1α抑制剂2-甲氧基雌二醇15 mg/kg。采用ELISA法检测血清乳酸脱氢酶、肌钙蛋白I、肌酸激酶同工酶、肌酐、尿素氮、中性粒细胞明胶酶相关脂质运载蛋白水平及肾组织肿瘤坏死因子-α、白细胞介素-6水平,采用TTC法检测心肌梗死面积,采用黄嘌呤氧化酶法检测肾组织超氧化物歧化酶活性,采用硫代巴比妥酸法检测肾组织丙二醛水平,采用HE染色观察肾组织病理变化并进行肾小管损伤评分,采用Western blot法检测肾组织HIF-1α、内皮型一氧化氮合酶、磷酸化内皮型一氧化氮合酶蛋白相对表达量。结果 再灌注120 min时,IR-M组、IRD-M组、IR组、IRD组、假手术组血清乳酸脱氢酶[(1 405.30±12.42)、(1 209.00±11.49)、(1 006.30±13.25)、(802.50±15.14)、(567.80±15.69)u/L]、肌酸激酶同工酶[(945.00±30.28)、(842.00±31.20)、(748.50±31.63)、(541.50±26.25)、(332.00±19.75)u/L]、肌钙蛋白I [(1.31±0.04)、(1.25±0.03)、(0.97±0.03)、(0.59±0.04)、(0.19±0.04)μg/L]水平及心肌梗死面积[(38.30±2.21)%、(37.50±2.52)%、(35.10±2.33)%、(18.30±3.74)%、(1.53±0.44)%]比较差异均有统计学意义(F=6.771~189.058,P均<0.05),且均依次降低(P<0.05);IR-M组、IRD-M组、IR组、IRD组、假手术组血清肌酐[(76.00±1.83)�Objective To construct renal injury mice models induced by myocardial ischemia-reperfusion(IR),to observe the expression of hypoxia-inducible factor-lα(HIF-la)in renal tissues,and to explore the influence of dexmedetomidine on IR-induced renal injury and its potential mechanisms.Methods Fifty healthy male C57BL/6 mice,weighing 20-30 g,were randomly divided into five groups with 10 mice in each group:the sham group,IR group,IR+dexmedetomidine group(IRD group),IR+HIF-1αinhibitor group(IR-M group),and IR+dexmedetomidine+HIF-1αinhibitor group(IRD-M group).The IR,IRD,IR-M and IRD-M groups were subjected to left anterior descending coronary artery ligation for 30 min followed by 120 min of reperfusion to establish myocardial IR induced renal injury models.The sham group was performed the same procedure,but the left anterior descending coronary artery was only looped without ligation.The IRD and IRD-M groups received 25μg/kg dexmedetomidine via intraperitoneal injection 30 min before ligation.The IR-M and IRD-M groups received 15 mg/kg HIF-lαinhibitor 2-methoxyestradiol via intraperitoneal injection 5 min before ligation.The serum levels of lactate dehydrogenase,troponin I,creatine kinase-MB,creatinine,urea nitrogen and neutrophil gelatinase-associated lipocalin,and the renal tissue levels of tumor necrosis factor-αand interleukin-6 were detected using ELISA.The myocardial infarction size was measured using the TTC method.The renal tissue superoxide dismutase activity was assessed using the WST method.The malondialdehyde level in renal tissues was measured using the TBA method.HE staining was performed to observe the pathological changes of renal tissues,and the renal tubular injury was scored.Western blot was used to detect the relative expressions of HIF-la,endothelial nitric oxide synthase(eNOS),and phosphorylated eNOS in renal tissues.Results After 120-min reperfusion,the serum lactate dehydrogenase levels[(1405.30±12.42),(1209.00±11.49),(1006.30±13.25),(802.50±15.14),(567.80±15.69)u/L],creatinekinase-MBl

关 键 词：心肌缺血再灌注损伤 肾损伤 右美托咪定 低氧诱导因子-1Α 小鼠 

分 类 号：R614[医药卫生—麻醉学]