氟伐他汀对大鼠肾脏缺血再灌注损伤NF-κB表达的影响

Effects of Fluvastatin on Expression of Nuclear Factor-κB in Renal Ischemia and Reperfusion Injury in Rats

目的探讨氟伐他汀对大鼠肾缺血再灌注损伤后核因子-κB(NF-κB)表达的影响。方法将36只大鼠随机分为假手术组、缺血再灌注组和氟伐他汀组,每组各12只。假手术组术前3 d每日用等量0.9%氯化钠注射液灌胃后,予2%戊巴比妥钠腹腔麻醉(45 mg/kg),用500 U肝素钠腹腔注射,游离双侧肾脏,切除右肾后缝合腹壁。缺血再灌注组实验过程与假手术组相同,但在右肾切除、左肾游离后行左肾缺血实验,将左肾动、静脉用血管钳夹闭45 min后恢复灌流。氟伐他汀组于术前3 d每日予氟伐他汀(2 mg/kg)灌胃,余实验过程同缺血再灌注组。术后处死大鼠检测血肌酐(Cr)、尿素(BUN),光镜下观察肾组织病理学改变,蛋白免疫印迹检测NF-κB蛋白表达。结果缺血再灌注组、氟伐他汀组与假手术组比较,Cr、BUN水平明显增高,NF-κB表达明显增高,肾组织病理学见肾小管损伤加重,差异有统计学意义(P<0.05)。氟伐他汀组与缺血再灌注组比较,上述肾脏损伤指标明显降低,差异有统计学意义(P<0.05)。结论氟伐他汀能减轻肾缺血再灌注损伤,其机制可能与抑制NF-κB的表达有关。

Objective To explore the effects of Fluvastatin on expression of Nuclear Factor-κB （NF-κB） in renal ischemia and reperfusion injury.Methods A total of 36 rats were randomly divided into sham operation group （group A,n =12）,ischemiareperfusion group （group B,n =12） and Fluvastatin group （group C,n =12）.In group A after 3 d of lavaging with equal amount of 0.9％ sodium chloride injection every day before operation,the rats were given intraperitoneal anesthesia with 2％ pentobarbital sodium （45 mg/kg） ; then 500 U heparin sodium were injected into abdominal cavity of rats,and the right kidney was cut and abdominal wall was sutured after dissociation of the bilateral kidneys.In group B the experimental process was the same with that in group A,but the left kidney undertook ischemia experiment after the right kidney excision and left kidney dissociation; the arteries and veins in left kidney were occluded with vascular clamp for 45 min,and then reperfusion was restored.In group C the experimental process was the same with that in group B,plus 3 d of lavaging with Fluvastatin （2 mg/kg） before operation.The rats were sacrificed after operation,the creatinine （Cr） and blood urea nitrogen （BUN） of renal function were determined,renal histopathological changes were observed under light microscope,and NF-κB protein expression was detected by Western blotting.Results In group B and C,the Cr and BUN levels and NF-κB protein expression were significantly increased,and damage of kidney tubules was aggravated by histopathology compared with those in group A.The difference was statistically significant （P ＜ 0.05）.The damage of kidney tubules in group C was significantly reduced compared with that in group B （P ＜ 0.05）.Conclusion Fluvastatin may alleviate renal ischemia-reperfusion injury,and its mechanism may be related to inhibiting the expression of NF-κB.