利拉鲁肽对胰岛素抵抗模型大鼠肾脏组织NOX4和P22phox表达的影响  

Effect of liraglutide on the expression of NOX4 and P22phox in renal tissues of insulin resistance rats

作　　者：吴明昊 郝向波 胡桂才[3] 高宇[4] 高山林 WU Minghao;HAO Xiangbo;HU Guicai(Department of Nephrology,Tangshan Gongren Hospital,Tangshan 063000,China)

机构地区：[1]唐山市工人医院肾内科,063000 [2]唐山市工人医院内分泌二科,063000 [3]承德医学院附属医院肾内科 [4]承德医学院附属医院内分泌科

出　　处：《中国糖尿病杂志》2019年第6期468-472,共5页Chinese Journal of Diabetes

摘　　要：目的观察利拉鲁肽对高脂饮食诱导的IR模型大鼠肾脏还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶4(NOX4)和P22phox mRNA表达的影响。方法 54只雄性Wistar大鼠随机分为正常对照组(NC,n=16)和高脂组(HF,n=38)。8周后采用清醒状态下高胰岛素-正葡萄糖钳夹实验判定IR造模成功。将高脂模型组随机分为单纯高脂组(IR,n=11)、利拉鲁肽100μg/(kg·d)组(L100,n=11)、利拉鲁肽200μg/(kg·d)组(L200,n=11)。NC组和IR组予等量生理盐水皮下注射。药物干预2周后,每组随机取5只行钳夹实验。结果 RT-PCR结果显示,与IR组和L100组比较,L200组NOX4和P22phox表达降低[(1. 57±0. 18)vs(1. 92±0. 20)、(2. 31±0. 21),(2. 30±0. 42)vs(4. 47±0. 41)、(4. 89±0. 38),P<0. 05]。电镜结果显示,利拉鲁肽干预组肾小球基底膜增厚均有所减轻,足突肿胀缓解,且L200组改善效果更为明显。结论利拉鲁肽呈剂量依赖性减轻IR大鼠肾脏氧化应激,从而改善肾脏功能,发挥肾脏保护作用,其机制可能与下调IR大鼠肾脏NOX4、P22phox表达有关。ObiectiveTo investigate the effect of liraglutide on the expression of NADPH oxidase subunits NOX4 and P22 phox in the kidney of insulin resistance(IR)rats.Methods 54 male Wistar rats were divided into control group(NC)and high-fat group. Insulin resistance was evaluated by hyperinsulinemic euglycemic clamp test after 8 weeks. High-fat group rats were randomly divided into IR group,liraglutide 100 μg/(kg·d)group(L100),liraglutide 200 μg/(kg·d)group(L200). Rats in NC group and IR group were given equivalent volume of normal saline by subcutaneous injection. Five rats were randomly chosen in each group and performed hyperinsulinemic euglycemic clamp after two weeks of intervention.Results RT-PCR test showed that,compared with IR and L100 group,the expression of NOX4 and P22 phox in L200 group were decreased[(1. 57±0. 18)vs(1. 92±0. 20),(2. 31±0. 21),(2. 30±0. 42)vs(4. 47±0. 41),(4. 89±0. 38),P<0. 05]. Electron microscopy showed that the glomerular basement membrane thickening was lessened and podocyte swelling was relieved in liraglutide intervention group,especially in the L200 group.ConclusionLiraglutide can reduce the oxidative stress in the kidney of IR rats in a dose-dependent manner,thus improving renal function and exerting protective effects. The mechanism may be related to down-regulation of NOX4 and P22 phox expression.

关 键 词：利拉鲁肽 胰岛素抵抗 还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶 氧化应激 

分 类 号：R965[医药卫生—药理学] R-332[医药卫生—药学]