马来酸依那普利叶酸片对糖尿病大鼠发生对比剂肾病的影响及初步机制研究  

Effects of Enalapril Maleate and Folic Acid Tablets on Contrast-induced Nephropathy in Diabetic Rats and Related Mechanism

作　　者：侯建同 鄢高亮[1] 王栋[1] 乔勇[1] 朱伯谦[1] 刘波[1] 罗二飞 汤成春[1] HOU Jiantong;YAN Gaoliang;WANG Dong;QIAO Yong;ZHU Boqian;LIU Bo;LUO Erfei;TANG Chengchun(Department of Cardiology,Zhongda Hospital of Southeast University School,Nanjing (210009),Jiangsu,China)

机构地区：[1]东南大学附属中大医院心内科,江苏省南京市210009

出　　处：《中国循环杂志》2019年第1期96-101,共6页Chinese Circulation Journal

基　　金：国家自然科学基金(81600227)

摘　　要：目的:探讨马来酸依那普利叶酸片(EF)对糖尿病大鼠发生对比剂肾病(CIN)的影响及其初步机制。方法 :将32只雄性SD大鼠随机分为对照组,对照+EF组, CIN组, CIN+EF组,每组8只。CIN组及CIN+EF组通过腹腔内注射链脲佐菌素(60 mg/kg)建立早期糖尿病模型。对照+EF组及CIN+EF组在诱导CIN前用EF[30 mg/2.4mg/(kg·d)]连续灌胃7天,对照组和CIN组以等量生理盐水灌胃7天。通过尾静脉依次注射吲哚美辛(10 mg/kg),N-硝基-L-精氨酸甲酯(L-NAME,10 mg/kg),碘普罗胺(10 ml/kg)建立CIN模型。建立CIN模型2天后处死大鼠,检测各组大鼠生化指标、肾组织病理改变、细胞凋亡发生及整合素连接激酶(ILK)在血清及肾脏内表达情况。结果 :与对照组比,CIN组血清肌酐(Scr)、尿素氮(BUN)、同型半胱氨酸(Hcy)、ILK、血管紧张素Ⅱ(AngⅡ)水平、肾组织病理损伤评分、细胞凋亡指数及ILK蛋白表达均明显升高(P均<0.05);与对照组比,对照+EF组上述指标差异均无统计学意义(P均>0.05)。与CIN组比,CIN+EF组Scr、BUN、Hcy、ILK、AngⅡ水平、肾组织病理损伤评分、细胞凋亡指数及ILK蛋白表达均明显降低(P均<0.05)。结论 :EF对糖尿病大鼠发生CIN具有保护作用,其机制可能是通过降低AngⅡ、ILK及Hcy水平发挥肾脏保护作用。Objectives: To investigate the effects of enalapril maleate and folic acid tablets(EF) on contrast-induced nephropathy(CIN) in diabetic rats and explore the related mechanisms.Methods: 32 male SD rats were randomly divided into four groups: control group(CTL), control+EF group, CIN group, CIN+EF group. The early diabetic model was established by intraperitoneal injection of streptozotocin(60 mg/kg) in CIN group and CIN+EF group. Rats in control+EF and CIN+ EF group were treated with enalapril maleate and folic acid tablets [30 mg/2.4 mg/(kg·d)] for 7 consecutive days prior CIN induction, rats in CTL and CIN groups were treated with same amount of saline for 7 days. CIN was induced by sequential tail vein administration of indomethacin(10 mg/kg), L-NAME(10 mg/kg), and loperamide(10 ml/kg). Rats were sacrificed at 2 days after induction of CIN and the biochemical indexes, pathological changes, apoptosis and ILK protein expression in serum and kidney were measured. Results: Serum creatinine(Scr), blood urea nitrogen(BUN), homocysteine(Hcy), ILK, Angiotensin Ⅱ(Ang Ⅱ)level,pathological damage score, apoptosis index and ILK protein expression in CIN group were significantly increased compared with those of the control group(P<0.05). Scr, BUN,Hcy, ILK, AngII level,pathological damage score, apoptosis index and ILK protein expression were significantly decreased in CIN+EF group compared with those of the CIN group(P<0.05).Conclusions: The EF may play a protective role against contrast-induced nephropathy in diabetic rats, and its mechanism may be mediated through the reduction of AngII、ILK, Hcy levels.

关 键 词：马来酸依那普利叶酸片 糖尿病 对比剂肾病 

分 类 号：R54[医药卫生—心血管疾病]