达格列净对大鼠造影剂肾病的保护作用及机制

Protective effect and mechanism of Dapagliflozin on contrast-induced nephropathy in rats

目的 探讨达格列净对大鼠造影剂肾病(CIN)的保护作用及作用机制。方法 SD大鼠随机分为正常组、CIN模型组、达格列净组,采用尾静脉注射吲哚美辛、左旋硝基精氨酸甲酯、碘海醇注射液制备急性肾损伤大鼠模型,达格列净组于造模前2 h灌胃给予达格列净,正常组、模型组灌胃给予等体积生理盐水。造模24 h后分别检测大鼠血清肌酐(Scr)、尿素氮(BUN)、尿肌酐(Ucr)、24 h尿量,计算肌酐清除率;检测大鼠肾组织超氧化物歧化酶(SOD)、丙二醛(MDA)的含量;苏木素-伊红(HE)染色观察大鼠肾组织病理损伤情况;免疫荧光染色观察大鼠肾组织核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)的表达情况。结果 达格列净组Scr、BUN、肾组织MDA含量显著降低(与模型组比较,P<0.01或P<0.05),肌酐清除率、肾组织SOD含量显著提高(与模型组比较,P<0.05)。病理结果显示达格列净组大鼠肾小管上皮细胞变性区域明显减少。造影剂肾损伤后肾小管细胞HO-1、Nrf2表达均有轻度代偿性升高,达格列净干预后其表达量明显增多(与模型组比较P<0.01)。结论 达格列净对大鼠CIN有一定的保护作用,机制可能与增加Nrf2、HO-l蛋白的表达、提高大鼠抗氧化应激能力有关。

Objective To study the protective effect and mechanism of Dapagliflozin on contrast-induced nephropathy(CIN)in rats.Methods SD rats were randomly divided into normal control group,CIN model group and Dapagliflozin group.The model of acute kidney injury was established by tail vein injection of indomethacin,L-nitroarginine methyl ester and iohexol injection by gavage.Dapagliflozin group was gavaged with Dapagliflozin 2 hours before modeling,and the normal group and model group were gavaged with the same volume of saline.The serum creatinine(Scr),urea nitrogen(BUN),urinary creatinine(Ucr)and 24-hour urine volume of rats were measured after 24 hours of modeling,and the creatinine clearance rate was calculated.The contents of superoxide dismutase(SOD)and malondialdehyde(MDA)in rat kidney tissue were measured.HE staining was used to observe the pathological damage of rat kidney tissue.Immunofluorescence staining was used to observe the expression of nuclear factor E2 related factor 2(Nrf2)and heme oxygenase 1(HO-1).Results The contents of Scr,BUN and MDA in renal tissue were significantly decreased(P<0.01 or P<0.05 compared with the model group),while the creatinine clearance rate and the content of SOD in renal tissue were significantly increased(P<0.05 compared with the model group).Pathological results showed that the degeneration area of renal tubular epithelial cells in the Dapagliflozin group was significantly reduced.The expression of HO-1 and Nrf2 in renal tubular cells was slightly increased after kidney injury induced by contrast medium,and the expression level was significantly increased after the intervention of Dapagliflozin(P<0.01 compared with the model group).Conclusion Dapagliflozin has a certain protective effect on CIN rat,which may be related to increasing the expression of Nrf2 and HO-l proteins and improving the antioxidant stress ability of rats.