恩格列净对大鼠造影剂相关急性肾损伤的作用及其机制

Effect of empagliflozin on contrast-associated acute kidney injury in rats and its mechanism

目的:观察恩格列净(empagliflozin,EMPA)对大鼠造影剂相关急性肾损伤(contrast-associated acute kidney injury,CA-AKI)的影响,并探讨其可能的机制。方法:40只健康雄性SD大鼠随机分对照(control)组、EMPA组、CA-AKI组和CA-AKI+EMPA组,每组10只。分别给予相应干预措施,检测肾脏功能,病理染色观察肾脏组织损伤情况,并检测肾脏中细胞凋亡和氧化应激情况。结果:与对照组比较,大鼠注射造影剂后血清肌酐(serum creatinine,SCr)、血尿素氮(blood urea nitrogen,BUN)和胱抑素C(cystatin C,Cys-C)升高,肌酐清除率(creatinine clearance rate,CLCR)水平降低,以12 h后变化显著(P<0.01)。与CA-AKI组比较,恩格列净显著减轻大鼠肾脏功能损害,SCr降低,CLCR水平升高(P<0.01)。恩格列净干预后,造影剂诱导的大鼠肾小管病理损伤评分降低(P<0.01),肾脏组织细胞凋亡率显著下降(P<0.01),肾脏促凋亡蛋白(caspase-3、Bax和Cyt-C)表达减少且抗凋亡蛋白Bcl-2表达显著增加(P<0.01)。此外,与CA-AKI组比较,恩格列净还可增加大鼠肾脏组织超氧化物歧化酶活性(P<0.01),降低丙二醛含量(P<0.01)。结论:恩格列净可能通过抑制细胞凋亡和氧化应激,减轻造影剂对大鼠肾脏的损伤,从而预防造影剂相关急性肾损伤的发生发展。

AIM:To investigate the therapeutic effect of empagliflozin(EMPA)on contrast-associated acute kidney injury(CA-AKI)and explore the underling mechanism in rats.METHODS:Forty healthy male Sprague-Dawley(SD)rats were randomly divided into control,EMPA,CA-AKI and CA-AKI+EMPA group.After the intervention,the renal function and renal pathological damage were observed.In addition,the apoptosis and oxidative stress in kidney were also detected.RESULTS:The serum creatinine(SCr),blood urea nitrogen(BUN)and cystatin C(Cys-C)were increased,whereas the endogenous creatinine clearance rate(CLCR)was decreased after injection of contrast medium,which were significantly changed after 12 h(P<0.01).Compared with the CA-AKI group,empagliflozin significantly improved the renal function in rats,SCr was decreased and CLCR was increased(P<0.01).After treated with empagliflozin,the pathological damage score of renal tubules was decreased(P<0.01),the renal apoptosis rate was significantly decreased(P<0.01),the expression levels of pro-apoptotic proteins(caspase-3,Bax and Cyt-C)were decreased(P<0.01),and the level of anti-apoptotic protein Bcl-2 was significantly increased(P<0.01).Additionally,compared with the CA-AKI group,empagliflozin increased the activity of superoxide dismutase(SOD)and decreased the malondialdehyde(MDA)content in the kidney(P<0.01).CONCLUSION:Empagliflozin might attenuate the renal damage induced by contrast medium and prevent the occurrence of CA-AKI via inhibiting renal cell apoptosis and oxidative stress in rats.