摘要目的 评价青藤碱对大鼠肾缺血再灌注时低氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)表达的影响.方法 健康成年雄性Wistar大鼠54只,体重180～ 220 g,采用随机数字表法分为3组(n=18):假手术组(S组)、肾缺血再灌注组(I/R组)和青藤碱组(SIN组).I/R组和SIN组采用夹闭左侧肾蒂45 min恢复灌注的方法制备大鼠肾缺血再灌注损伤模型.S组仅游离双侧肾蒂.SIN组于再灌注前30 min腹腔注射青藤碱注射液60 mg/kg,S组和I/R组腹腔注射等容量生理盐水.于再灌注6、12和24 h(T1-3)时每组随机取6只大鼠采集心脏血样,测定血清Cr和BUN浓度,随后处死大鼠取左肾,石蜡包埋,采用免疫组化法检测肾组织HIF-1α和VEGF的表达水平.结果 与S组比较,I/R组和SIN组T1-3时血清Cr和BUN浓度升高,T23时肾组织HIF-1α表达上调,I/R组T2.3时、SIN组T1-3时VEGF表达上调(P＜0.05);与I/R组比较,SIN组T1-3时血清Cr浓度和T2,3时血清BUN浓度降低,T2,3时肾组织HIF-1α和T1-3时VEGF表达上调(P＜0.05).结论 青藤碱减轻大鼠肾缺血再灌注损伤的机制与其上调肾组织HIF-1α和VEGF表达有关.

abstractsObjective To evaluate the effects of sinomenine on the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) during renal ischemia-reperfusion (I/ R) in rats.Methods Fifty-four male Wistar rats, weighing 180-220 g, were randomly divided into 3 groups (n=18 each) using a random number table: sham operation group (group S) , group I/R and sinomenine group (group SIN).Renal I/R was induced by clamping the left renal pedicle for 45 min followed by reperfusion in I/R and SIN groups.In group S, the bilateral renal pedicels were only exposed.Sinomenine 60 mg/kg was intraperitoneally injected at 30 min before reperfusion in group SIN, while the equal volume of normal saline was given in group S and group I/R.At 6, 12 and 24 h (T1-3) of reperfusion, 6 rats from each group were chosen, and blood samples were drawn from the hearts for determination of the serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations.The animals were then sacrificed, and the left kidney was removed and embedded into a paraffin block for determination of the expression of HIF-1α and VEGF in the renal tissues (by immuno-histochemistry).Results Compared with group S, the serum Cr and BUN concentrations were significantly increased at T1-3 , and the expression of HIF-1α was significantly up-regulated at T2,3 in group I/R and group SIN, and the expression of VEGF was significantly upregulated at T2,3in group I/R, and at T1-3 in group SIN.Compared with group I/R, the serum Cr concentration at T1-3 and serum BUN concentration at T2,3 were significantly decreased and the expression of HIF-1α at T2,3and VEGF at T1-3was significantly up-regulated in group SIN.Conclusion The mechanism by which sinomenine attenuates renal I/R injury is related to up-regulation of the expression of HIF-1α and VEGF in the renal tissues of rats.