CAJ | 학술논문

目的评价缺血后处理对小鼠肠缺血再灌注致肾损伤时核因子E2相关因子2(Nrf2)蛋白表达的影响.方法健康雄性C57BL/6J小鼠36只,9～12周,采用随机数字表法,将其随机分为3组(n=12):假手术组(S组)、缺血再灌注组(I/R组)、缺血后处理+缺血再灌注组(IPO组).采用夹闭肠系膜上动脉根部45 min恢复灌注的方法制备小鼠肠缺血再灌注损伤模型,IPO组于缺血45 min时再灌注30s,缺血30s,重复3次后恢复灌注.于再灌注2h时采集颈动脉血样,然后处死小鼠,取肾组织,测定血清BUN、Cr和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平,检测肾组织Nrf2和HO-1蛋白表达、MDA含量、SOD活性、TNF-α、IL-6和IL-10的含量.显微镜下观察肾组织病理学结果,并行病理学损伤评分.结果与S组比较,I/R组血清BUN、Cr和NAGL浓度升高,肾脏组织Nrf2及HO-1蛋白表达上调,MDA含量升高,SOD活性降低,肾脏组织病理学损伤评分升高(P＜0.05)；与I/R组比较,IPO组血清BUN、Cr和NAGL浓度降低,肾脏组织Nrf2及HO-1蛋白表达上调,MDA含量降低,SOD活性升高,肾脏组织病理学损伤评分降低(P＜0.05).各组肾脏组织TNF-α、IL-6和IL-10含量比较差异无统计学意义(P＞0.05).结论缺血后处理可减轻小鼠肠缺血再灌注致肾损伤,其机制可能与促进Nrf2蛋白表达,从而上调HO-1蛋白表达有关.
목적 평개결혈후처리대소서장결혈재관주치신손상시핵인자E2상관인자2(Nrf2)단백표체적영향.방법 건강웅성C57BL/6J소서36지,9～12주,채용수궤수자표법,장기수궤분위3조(n=12):가수술조(S조)、결혈재관주조(I/R조)、결혈후처리+결혈재관주조(IPO조).채용협폐장계막상동맥근부45 min회복관주적방법제비소서장결혈재관주손상모형,IPO조우결혈45 min시재관주30s,결혈30s,중복3차후회복관주.우재관주2h시채집경동맥혈양,연후처사소서,취신조직,측정혈청BUN、Cr화중성립세포명효매상관지질운재단백(NGAL)수평,검측신조직Nrf2화HO-1단백표체、MDA함량、SOD활성、TNF-α、IL-6화IL-10적함량.현미경하관찰신조직병이학결과,병행병이학손상평분.결과 여S조비교,I/R조혈청BUN、Cr화NAGL농도승고,신장조직Nrf2급HO-1단백표체상조,MDA함량승고,SOD활성강저,신장조직병이학손상평분승고(P＜0.05)；여I/R조비교,IPO조혈청BUN、Cr화NAGL농도강저,신장조직Nrf2급HO-1단백표체상조,MDA함량강저,SOD활성승고,신장조직병이학손상평분강저(P＜0.05).각조신장조직TNF-α、IL-6화IL-10함량비교차이무통계학의의(P＞0.05).결론 결혈후처리가감경소서장결혈재관주치신손상,기궤제가능여촉진Nrf2단백표체,종이상조HO-1단백표체유관.
Objective To investigate the effect of ischemic postconditioning (IPO) on renal injury induced by intestinal ischemia-reperfusion (I/R) and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in mice.Methods Thirty-six healthy male C57BL/6J mice,aged 9-12 weeks,were randomly divided into 3 groups ( n =12 each):sham operation group ( S group),I/R group,and IPO + I/R group ( group IPO).Intestinal I/R was produced by occlusion of superior mesenteric artery for 45 min followed by 2 h reperfusion.The mice underwent 3 cycles of 30 s reperfusion and 30 s ischemia at the end of 45 min ischemia before 2 h reperfusion.Blood samples were collected from carotid artery at 2 h of reperfusion and then the mice were sacrificed.The kidney was removed for microscopic examination.The pathological changes of the kidney were scored.The concentrations of serum blood urea nitrogen (BUN),creatinine (Cr) and neutrophil gelatinase-associated lipocalin (NGAL)were detected.The expression of Nrf2 and heme oxygenase- 1 ( HO- 1 ),superoxide dismutase (SOD) activity,and the content of malondialdehyde (MDA),TNF-α,IL-6 and IL-10 were determined in renal tissues.Results The concentrations of serum BUN,Cr and NGAL,MDA content and the expression of Nrf2 and HO- 1 were significantly higher,SOD activity was significantly lower,and the pathological score was significantly higher in group I/R that in group S ( P ＜ 0.05).The concentrations of serum BUN,Cr and NGAL and MDA content were significantly lower,the expression of Nrf2 and HO-1 and SOD activity were significantly higher,and the pathological score was significantly lower in group IPO that in group I/R ( P ＜0.05).There was no significant difference in the content of TNF-αα,IL-6 and IL-10 among all groups(P＞0.05).Conclusion IPO can alleviate the renal injury induced by intestinal I/R through promoting the expression of Nrf2 and up-regulating the expression of HO-1 in mice.