蛋白激酶C激活在兔内毒素休克诱发急性肾损伤中的作用  

Role of Protein Kinase C Activation in Endotoxic Shock-induced Acute Renal Injury in Rabbits

作　　者：张晓[1] 史佳[1] 余剑波[1] 宫丽荣[1] 张圆[1] 吴丽丽[1] 

机构地区：[1]天津医科大学南开临床学院天津市南开医院麻醉科,天津300100

出　　处：《中国中西医结合外科杂志》2016年第1期34-37,共4页Chinese Journal of Surgery of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金(81372096);天津市卫计委科技基金(2014KZ048);天津市卫生局级课题(2014KZ048)

摘　　要：目的:探讨蛋白激酶C(PKC)在兔内毒素休克诱发急性肾损伤中的作用及其可能作用机制。方法:健康清洁级雄性新西兰大白兔40只,采取随机数字表法分为对照组(CON组)、内毒素休克致急性肾损伤组(AKI组)、PKC-α阻断剂-白屈菜赤碱加AKI组(CHA)、PKC-α激活剂-佛波酯加AKI组(PMA)。PMA组经兔耳缘静脉注射佛波酯5μg/kg,CHA组静脉注射白屈菜赤碱5 mg/kg,CON组与AKI组注射各自溶媒1%DMSO 0.5 m L。30 min后,AKI组、PMA组及CHA组静脉注射脂多糖(LPS)5 mg/kg(溶于2 m L生理盐水),CON组给予等容量生理盐水。静脉注射LPS或生理盐水6 h时,采集动脉血,检测血清尿素氮(BUN)和肌酐(Cr)浓度,处死动物后取肾组织,进行病理学观察及肾损伤评分,测定肾组织PKC-α蛋白、HO-1蛋白、Nrf2核蛋白及总蛋白的表达水平。结果:与CON组比较,AKI组、CHA组及PMA组血清BUN、Cr浓度升高,肾组织病理学评分升高,PKC-α蛋白(1.37±0.26)、HO-1蛋白(0.89±0.11)、Nrf2核蛋白(0.97±0.26)及总蛋白的表达均上调(P<0.05);与AKI组比较,PMA组血清BUN、Cr浓度降低,肾组织病理学评分降低,PKC-α蛋白、HO-1蛋白、Nrf2核蛋白及总蛋白的表达均上调(P<0.05),CHA组血清BUN、Cr浓度升高,肾组织病理学评分(9.8±3.9)升高,PKC-α蛋白、HO-1蛋白、Nrf2核蛋白及总蛋白的表达均下调(P<0.05)。结论:PKC-α激活是内毒素休克诱发急性肾损伤时机体的适应性调节反应机制之一,其机制可能与激活Nrf2/ARE通路、上调HO-1的表达有关。ObjectiveTo investigate the role of（protein kinase C, PKC） activation in endotoxic shock-in-duced acute renal injury in rabbits.MethodsForty healthy male New Zealand white rabbits, weighing1.5-2.0 kg, aged 2 months, were randomly divided into 4 groups（n=10/each）： control group（CON）, endotoxicshock induced acute kidney injury group（AKI）, chelerythrine ＋ endotoxic shock induced acute kidney injurygroup（CHA） and phorbol＋ endotoxic shock induced acute kidney injury group（PMA）. Phorbol（5 μg/kg） was in-jected in PMA group, and chelerythrine（5 mg/kg） was injected in CHA group via auricular vein. Meanwhile, 1%DMSO was given in CON group and AKI group After 30 min, LPS（5 mg/kg, diluted to 2 ml in 0.9% normal sa-line） was injected intravenously in AKI, CHA and PMA groups, while the equal amount of normal saline was ad-ministered in CON group. The rabbits were sacrificed at 6h after LPS or normal saline administration. The kid-neys were removed for microscopic examination. The pathological changes of the kidney were scored. The con-centrations of serum urea nitrogen（BUN） and creatinine（Cr）, and the expressions of PKC-α protein, total nucle-ar factor erythroid 2-related factor 2（Nrf2） and nu-clear Nrf2, and HO-1 in renal tissue were detected.ResultsCompared with CON group, the patholog-ical scores, the levels of BUN and Cr, the expressionof PKC-α（1.37±0.26）, total and nuclear Nrf2（0.97±0.26）, and HO-1（0.89±0.11） in renal tissue were significantly increased in AKI, CHA, and PMA group（P〈0.05）. Compared with AKI group, the pathologicalscores and the levels of BUN and Cr were decreased, yet the expressions of PKC α protein, Nrf2 m RNA, Nrf2 to-tal and nuclear protein, HO-1 m RNA and protein were significantly increased in group PMA（P〈0.05）. Con-versely, the pathological scores（9.8±3.9） and the levels of BUN and Cr were increased, while the expressions ofPKC-α protein, Nrf2 m RNA, Nrf2 total and nuclear protein, HO-1 m RNA and protein were

关 键 词：蛋白激酶C 核因子NF-E2相关因子 血红素氧合酶-1 休克 脓毒性 急性肾损伤 

分 类 号：Q95-33[生物学—动物学] R692[医药卫生—泌尿科学]