光甘草定对大鼠对比剂急性肾损伤的保护作用及其主要机制研究

Protective Effects and Main Mechanisms of Glabridin on Rats with Contrast-induced Nephropathy

目的观察光甘草定对大鼠对比剂急性肾损伤的保护作用及其主要机制。方法将50只SD大鼠随机分为空白组、模型组、光甘草定高剂量组、中剂量组及低剂量组。采用优维显碘普罗胺(10 mg/kg)尾静脉注射法对除空白组外其他各组大鼠进行造模,造模后,光甘草定高剂量组、中剂量组及低剂量组大鼠分别灌胃给予200、100、50 mg/kg的光甘草定,空白组及模型组则给予等量生理盐水,各组均连续给药3 d。末次给药24 h后,采用尾静脉取血法取各组大鼠静脉血,检测其中血肌酐(Scr)及尿素氮(BUN)等肾功能指标含量。取血后取各组大鼠双侧肾,观察左侧肾病理组织学变化;将右侧肾脏分成4份,采用荧光免疫组化法观察其中血红素加氧酶(HO-1)、过氧化氢酶(CAT)、8-羟基脱氧鸟苷(8-OHDG)及髓过氧化物酶(MPO)的表达情况,并统计上述蛋白的相对表达量。结果与模型组比,空白组、光甘草定高剂量组、中剂量组及低剂量组大鼠Scr及BUN均明显降低(P <0.05)。HE染色结果显示,高剂量组、中剂量组及低剂量组大鼠呈现不同程度肾小球内皮细胞变性、肾小管结构破坏及肾间质炎性细胞浸润,但程度均不及模型组。荧光免疫组化染色中,光甘草定高剂量组、中剂量组及低剂量组大鼠肾组织中HO-1及CAT阳性表达情况明确强于模型组,而8-OHDG及MPO阳性表达情况明确弱于模型组。半定量分析结果表明,与模型组比较,高剂量组、中剂量组及低剂量组HO-1及CAT相对表达量均明显增高,而8-OHDG及MPO相对表达量均明显降低(P <0.05)。结论光甘草定可有效改善对比剂急性肾损伤大鼠肾脏功能,其主要机制可能与该化合物的抗氧化活性有关。

Objective:To observe the protective effects and main mechanisms of glabridin on rats with contrast-induced nephropathy.Methods:50SD mice were randomly divided into the blank group,the model group,the high dose group,the middle dose group and the low dose group.The method of iopproamine(injection dose10mg/kg)vein injection was used to build the model in the groups except the blank group.After the model was built,the high dose group,the middle dose group and the low dose group were treated by glabridin with the dose of200mg/kg,100mg/kg and50mg/kg,respectively,and other groups were treated by saline.The treatment continues for3days.24hours after the last treatment,the venous blood was obtained in the groups and renal function indexes,such as the levels of blood creatinine(Scr)and urea nitrogen(BUN),were detected.After the blood collection,the left and right kidneys were obtained.Then the histopathological changes were observed in left kidney.The right kidney was divided into four parts and the fluorescence immunohistochemistry was performed to observe the expression of heme oxygenase(HO-1),catalase(CAT),8-hydroxydeoxyguanosine(8-OHDG)and myeloperoxidase(MPO).Results:Compared with the model group,the levels of Scr and BUN were significantly lower in the high-dose group,the middle-dose group and the low-dose group(P<0.05).The results of HE staining showed that the rats in the high-dose group,the middle-dose group and the low-dose group showed varying degrees of glomerular endothelial degeneration,renal tubule structure destruction and renal interstitial inflammatory cell infiltration,but the degree was less than the model group.In the fluorescent immunohistochemical staining,the positive expression of HO-1and CAT in the kidney tissues of the high-dose group,the middle-dose group and the low-dose group was clearly stronger than that of the model group,while the positive expression of8-OHDG and MPO was clearly weaker than that in the model group.The results of semi-quantitative analysis showed that compared with the model group,the relative expression of HO-1and CAT in high-dose group,the middle-dose group and the low-dose group increased significantly,while the relative expression of8-OHDG and MPO decreased significantly(P<0.05).Conclusion:Glabridin can promote the renal function of rats with contrast-induced nephropathy and its main mechanism may be related to its antioxidant activity.