吴明昊, 刘剑, 胡桂才, 高宇, 张宝红, 周瑾, 赵亚娟. 利拉鲁肽对胰岛素抵抗大鼠肾脏8-羟基脱氧鸟苷、丙二醛及超氧化物歧化酶表达的影响[J]. 临床肾脏病杂志, 2017, 17(3): 177-180. DOI: 10.3969/j.issn.1671-2390.2017.03.010
    引用本文: 吴明昊, 刘剑, 胡桂才, 高宇, 张宝红, 周瑾, 赵亚娟. 利拉鲁肽对胰岛素抵抗大鼠肾脏8-羟基脱氧鸟苷、丙二醛及超氧化物歧化酶表达的影响[J]. 临床肾脏病杂志, 2017, 17(3): 177-180. DOI: 10.3969/j.issn.1671-2390.2017.03.010
    WU Ming-hao, LIU Jian, HU Gui-cai, GAO Yu, ZHANG Bao-hong, ZHOU Jin, ZHAO Ya-juan. Effects of liraglutide on 8-OHdG, MDA and SOD of kidney in insulin resistance rats[J]. Journal of Clinical Nephrology, 2017, 17(3): 177-180. DOI: 10.3969/j.issn.1671-2390.2017.03.010
    Citation: WU Ming-hao, LIU Jian, HU Gui-cai, GAO Yu, ZHANG Bao-hong, ZHOU Jin, ZHAO Ya-juan. Effects of liraglutide on 8-OHdG, MDA and SOD of kidney in insulin resistance rats[J]. Journal of Clinical Nephrology, 2017, 17(3): 177-180. DOI: 10.3969/j.issn.1671-2390.2017.03.010

    利拉鲁肽对胰岛素抵抗大鼠肾脏8-羟基脱氧鸟苷、丙二醛及超氧化物歧化酶表达的影响

    Effects of liraglutide on 8-OHdG, MDA and SOD of kidney in insulin resistance rats

    • 摘要: 目的 研究利拉鲁肽对胰岛素抵抗(insulin resistance,IR)大鼠肾脏8-羟基脱氧鸟苷(8- hydroxydeoxyguanosine,8-OHdG)、丙二醛(malonaldehyde,MDA)及超氧化物歧化酶(superoxide dismutase,SOD)含量的影响。方法 54只雄性Wistar大鼠随机分成对照组(普通饮食)16只、模型组(高脂饮食)38只。喂养8周末各组取5只行高胰岛素-正葡萄糖钳夹实验评价各组IR状态,判定IR造模成功后再将高脂喂养组随机分为IR组、干预组1(利拉鲁肽100 μg·kg-1·d-1)、干预组2(利拉鲁肽200 μg·kg-1·d-1)。药物干预2周后,测定各组大鼠血肌酐(serum creatinine,SCr)、尿素氮(blood urea nitrogen,BUN)、24 h尿蛋白量以及肾组织中8-OHdG、MDA和SOD含量,并应用电镜观察各组肾组织形态结构。结果 IR组的SCr、BUN、24 h尿蛋白定量、8-OHdG、MDA分别为(26.31±0.60)μmol/L、(10.43±0.50)mmol/L、(7.13±0.60)mg、(32.81±2.96)ng/L和(7.7±1.0)nmol/mg,与对照组(15.55±0.42)μmol/L、(5.34±1.33)mmol/L、(2.18±0.29)mg、(13.30±1.72)ng/L、(3.3±0.4)nmol/mg比较均明显升高(均P<0.05),而SOD表达下降(175.0±7.7)U/mg比(237.1±12.4)U/mg,P<0.05);与IR组比较,干预组1的24 h尿蛋白定量(6.46±0.44)mg、8-OHdG(28.54±2.71)ng/L、MDA(6.6±1.0)nmol/mg表达均减少(均P<0.05);与IR组比较,干预组2的SCr(24.07±1.05)μmol/L、BUN(9.53±0.53)mmol/L、24 h尿蛋白定量(4.60±0.40)mg、MDA(5.7±0.5)nmol/mg、8-OHdG(20.06±1.65)ng/L表达均降低(均P<0.05),而SOD(216.1±10.6)U/mg表达升高(P<0.05);与干预组1比较,干预组2的SCr、BUN、24 h尿蛋白量、MDA、8-OHdG均降低(均P<0.05),而SOD表达升高(P<0.05)。结论 利拉鲁肽可呈浓度依赖性降低肾脏氧化应激水平,可能是阻断IR所致肾损伤的原因之一。

       

      Abstract: Objective To observe the effects of liraglutide on 8-OHdG, MDA and SOD of kidney in insulin resistance (IR) rats.Methods According to random number table method, 54 Wistar male rats were divided into normal control group (normal diet) and IR model group (high fat diet). IR was evaluated by hyperinsulinemic euglycemic clamp technique after 8 weeks. After IR rat models were successfully established, the animals in high fat diet group were randomly divided into IR group, intervention group 1 (liraglutide: 100 μg·kg-1·day-1), and intervention group 2 (liraglutide: 200 μg·kg-1·day-1). After treatment for 2 weeks with liraglutide, SCr, BUN, 24-h urine protein, and 8-OHdG, MDA and SOD in the renal tissues were determined. The morphology and structure in the renal tissues were observed by electron microscope.Results As compared with control group, the levels of SCr, BUN, 24-h urine protein, 8-OHdG, and MDA were significantly increased in IR group (8-OHdG: 32.81±2.96 ng/L vs. 13.30±1.72 ng/L; MDA: 7.7±1.0 nmol/mg vs. 3.3±0.4 nmol/mg, all P<0.05) and the expression of SOD was decreased (175.0±7.7 U/mg vs. 237.1±12.4 U/mg, P<0.05). As compared with the IR group, 24-h urine protein, 8-OHdG and MDA were decreased in intervention group 1 (8-OHdG: 28.54±2.71 ng/L vs. 32.81±2.96 ng/L; MDA: 6.6±1.0 nmol/mg vs. 7.7±1.0 nmol/mg, P<0.05); SCr, BUN, 24-h urine protein, MDA and 8-OHdG were decreased (8-OHdG: 20.06±1.65 ng/L vs. 32.81±2.96 ng/L; MDA: 5.7±0.5 nmol/mg vs 7.7±1.0 nmol/mg, all P<0.05) and SOD was increased in intervention group 2 (216.1±10.6 U/mg vs. 175.0±7.7 U/mg, P<0.05). As compared with the intervention group 1, SCr, BUN, 24-h urine protein, MDA and 8-OHdG were decreased (all P<0.05) and SOD was increased in intervention group 2 (P<0.05).Conclusions Liraglutide could decrease the kidney oxidative stress in a concentration-dependent manner, which may be one of the reasons for the renal injury induced by IR.

       

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