不同剂量维生素C药物后处理对肾缺血再灌注损伤的影响

Effects of Postprocessing of Different Dosages of Vitamin C on Renal Ischemia-reperfusion Injury in Rats

目的研究不同剂量维生素C药物后处理对肾缺血再灌注损伤的影响及核因子-κB亚基p65亲和肽(NF-κBp65)在肾缺血再灌注损伤中的相关机制。方法成年雄性SD大鼠30只,随机分为5组,每组6只。分别为:假手术组(Sham组),肾脏缺血再灌注组(RIR组),维生素C药物后处理低剂量组(LVcPO组)、中剂量组(MVcPO组)、高剂量组(HVcPO组)。各组动物于再灌注2h时取血,检测血尿素氮(BUN)和肌酐(Cr);同时留取肾组织进行匀浆,测定匀浆中超氧化物歧化酶(SOD)活性、丙二醛(MDA)和NO水平;制作肾组织石蜡切片,免疫组化法测肾组织中NF-κBp65表达情况。结果与Sham组比较,RIR组血BUN、Cr水平,肾组织MDA、NO水平增高;SOD活性降低(P<0.01)。与RIR组比较,LVcPO组、MVcPO组、HVcPO组的血BUN、Cr水平,肾组织MDA、NO水平降低(P<0.05),SOD活性有所上升(P<0.05)。RIR组NF-κBp65在肾小管上皮细胞阳性表达明显,有大量棕黄色颗粒,呈弥漫性分布,LVcPO组、MVcPO组、HVcPO组阳性细胞较Sham组增多,但较RIR组明显减少,其中以HVcPO组阳性细胞最少。结论肾组织中NF-κB的表达及NO水平的改变与缺血再灌注引起的肾组织损伤有密切关系。经过不同剂量维生素C后处理,抑制了肾组织中NF-κBp65的表达,减少了NO水平,进而对肾组织起着有效的保护作用,且发现高剂量维生素C后处理有更为明显的保护效果。

Objective To investigate the effects of postprocessing of different dosages of vitamin C on renal ischemia - reperfusion injury and the relevant mechanisms of NF -κB 1365 in rats. Methods Thirty adult male SD rats were divided randomly into groups Sham, renal ischemia - reperfusion group （RIR） , postprocessing of low - dosage Vitamin C （LVcPO） , mid- dle -dosage （MVcPO） and high -dosage （HVcPO）, 6 in each. Serum was collected to detect blood urea nitrogen （BUN） and creatinine （Cr） at hours 2 after reperfusion, and renal tissues were taken to perform homogenate to determine the levels of superoxide dismutase （SOD） activities, malondialdehyde （MDA） and NO. The NF -κB p65 levels in renal tissue were evaluated by immunohistochemical method. Results The levels of BUN, Cr, renal tissue MDA, NO increased （ P 〈 0. 01 ） but SOD decreased in group RIR （P 〈0. 01） as compared with group Sham; those of groups LVcPO, MVcPO, HVcPO decreased （P 〈 0.05）, but SOD increased （P 〈 0. 05 ）, when compared with group RIR. NF -κB p65 of group RIR had remarkable positive expression in renal tubular epithelial cells, with a large number of brown - yelllow granules distributing in a diffusing state. Positive cells were more in groups LVcPO, MVcPO, HVcPO than in group Sham, but fewer than in group RIR, the fewest in group HVcPO. Conclusion NF-κB p65 expression and changes of NO level in renal tisssues are closely related to ischemia - reper- fusion - induced renal tissue damage. Postprocessing of different dosages of vitamin C inhibits NF-κB p65 expression and reduces NO level, thus to protect effectively renal tissues. It has been found that postprocessing of high - dosage vitamin C can effect more remarkably.