【摘要】 目的 探讨乌司他丁对大鼠肾缺血/再灌注(I/R)损伤的作用及其机制。方法 雄性SD大鼠75只,随机分为三组:假手术对照组(C组)、肾I／R组(I组)、乌司他丁组(U组),每组25只。I组和U组大鼠夹闭双侧肾蒂45min后重新开放肾脏血供,制作肾脏I／R模型,C组不夹闭双侧肾蒂。U组缺血前30 min及再灌注开始时静脉注射乌司他丁1.25万单位,I组分别静脉注射生理盐水1 ml。各组在再灌注后0、2、6、12、24 h时取标本,测定血尿素氮(BUN)和血肌酐(Cr)浓度,并制备肾脏病理切片,采用免疫组化方法测定热休克蛋白70(HSP70)和bcl-2蛋白的表达。结果 与I组比较,C组在再灌注后各时点血清BUN和Cr浓度均降低(P<0.05),U组在再灌注后12、24 h时血清BUN和Cr浓度也降低(P<0.05)。C组肾脏未发现明显的形态学改变;I组近曲小管上皮细胞空泡变性和坏死,肾小管腔扩张,内可见管型和坏死脱落细胞,可见管周血管明显扩张淤血;U组近曲小管上皮细胞肿胀、颗粒变性,罕见管型,管周稍有淤血。与I组比较,C组在再灌注后0、6、12、24 h时Paller评分降低(P<O.05),U组在再灌注后0、6、24 h时Paller评分也降低(P<0.05),C组再灌注后12、24 h时HSP 70表达降低(P<0.05),U组在再灌注后6、24h时bcl-2蛋白表达增强(p<0.05)。结论 乌司他丁对肾脏I／R损伤有保护作用,其机?更多还原

【Abstract】 Objective To investigate the effects of ulinastatin on renal ischemia/reperfusion (I/R) in rats and assess the possible mechanism. Methods Seventy-five male SD rats weighing 210-250 g were randomly divided into three groups with 25 animals in each group : (Ⅰ) control group received sham operation; (Ⅱ)renal I/R group and (Ⅲ) ulinastatin + I/R group. The animals were anesthetized with intraperitoneal ketamine 50 mg·kg-1 . Bilateral kidneys were exposed through midline incision and bilateral renal pedicles were occluded with atraumatic mini-clamp. The kidneys turned pale. In control group the kidneys were exposed but their pedicles were not clamped, while in ulinastatin group (Ⅲ) ulinastatin 12 500 u was given i. v. 30 min before ischemia and at the beginning of reperfusion. Blood samples and kidneys were obtained at 0, 2, 6, 12, 24 h of reperfusion for determination of blood urea nitrogen (BUN) and serum creatinine (Cr) concentrations and the expression of heat shock protein 70 (HSP 70) and bcl-2 in kidney and for microscopic examination. Paller scoring system was used to evaluate the severity of histological changes ( the higher the score, the worse is the change) .Results BUN and serum Cr levels were significantly lower at 12 and 24 h of reperfusion in group Ⅲ than in group Ⅱ (P < 0.05). The mean Paller score was significantly lower in group Ⅲ than that in group Ⅱ at 0, 6 and 24 h of reperfusion ( P <0.05). The renal bcl-2 expression was significantly higher in group Ⅲ than that in group Ⅱ at 6 and 24h of reperfusion (P < 0.05). There was no significant difference in renal HSP 70 expression between group Ⅱ and Ⅲ (P > 0.05) . Conclusion Ulinastatin can reduce the risk of renal dysfunction and injury associated with renal I/ R. The protective effect of ulinastatin may be associated with the up-regulation of bcl-2 expression.更多还原