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目的探讨依布硒啉(ebselen)对db/db小鼠蛋白尿的作用及其可能机制。方法 16只8周龄db/db小鼠随机分为依布硒啉组8只(Ebs组)和糖尿病肾病组8只(DN组),分别给予依布硒啉50mg/kg和生理盐水灌胃,2次/d;8只8周龄db/m小鼠为非糖尿病对照组(对照组),给予生理盐水灌胃,2次/d;每周监测各组体质量、空腹血糖。8周后检测24h尿白蛋白、尿8-羟基脱氧鸟苷酸、肾脏组织丙二醛含量、超氧化物歧化酶和谷胱甘肽过氧化物酶活性。结果治疗8周后,DN组空腹血糖((31.9±2.4)mmol/L)、24h尿白蛋白((240.7±26.3)μg/24h)、尿8-羟基脱氧鸟苷酸(183.5±26.7)ng/24h)、肾组织匀浆丙二醛含量((11.5±2.2)nmol/mg)明显高于对照组((6.7±0.8)mmol/L、(16.4±1.1)μg/24h、(74.8±13.5)ng/24h、(3.6±0.9)nmol/mg)和Ebs组((21.3±1.1)mmol/L、(76.3±14.7)μg/24h、(86.9±16.5)ng/24h、(7.7±1.6)nmol/mg),肾脏组织超氧化物歧化酶和谷胱甘肽过氧化物酶活性((312.4±16.9)、(167.2±14.8)u/mg)明显低于对照组((358.2±13.4)、(217.4±15.7)u/mg)和Ebs组((366.5±24.7)、(191.2±16.5)u/mg)(P<0.01);Ebs组空腹血糖、24h尿白蛋白和肾组织丙二醛含量高于对照组(P<0.01),尿8-羟基脱氧鸟苷酸水平、超氧化物歧化酶和谷胱甘肽过氧化物酶活性与对照组比较差异无统计学意义(P>0.05)。结论依布硒啉能降低蛋白尿,其机制可能与减轻db/db小鼠肾脏组织氧化应激有关。
Objective To investigate the effect of ebselen on proteinuria in db / db mice and its possible mechanism. Methods Sixteen 8-week-old db / db mice were randomly divided into Ebselen group (n = 8) and diabetic nephropathy group (n = 8) , 2 times / d. Eight 8-week-old db / m mice were non-diabetic control group (control group). Rats were given normal saline intragastrically for 2 times daily. Body mass and fasting blood glucose were monitored weekly. Urine albumin, urine 8-hydroxydeoxyguanosine, malondialdehyde content in renal tissue, superoxide dismutase and glutathione peroxidase activity were detected after 8 weeks. Results After 8 weeks of treatment, the levels of fasting blood glucose (31.9 ± 2.4) mmol / L, 24 h urinary albumin (240.7 ± 26.3 μg / 24h), urinary 8-hydroxydeoxyguanosine (183.5 ± 26.7) ng / (24.4 ± 1.1) μg / 24h and (74.8 ± 13.5) / ml respectively), and the content of malondialdehyde in renal tissue homogenate was (11.5 ± 2.2) nmol / ) were significantly higher than those in the Ebs group (21.3 ± 1.1 mmol / L, (76.3 ± 14.7) μg / 24h, (86.9 ± 16.5) ng / 24h and (7.7 ± 1.6) ng / nmol / mg), the activities of superoxide dismutase and glutathione peroxidase in kidney tissue were (312.4 ± 16.9) and (167.2 ± 14.8) u / mg, respectively, which were significantly lower than those in control group (358.2 ± 13.4) (217.4 ± 15.7) u / mg) and Ebs group (366.5 ± 24.7) and (191.2 ± 16.5) u / mg respectively (P <0.01). The levels of fasting blood glucose, 24h urinary albumin and malondialdehyde (P <0.01). The levels of urine 8-hydroxydeoxyguanosine, superoxide dismutase and glutathione peroxidase were not significantly different from those of the control group (P> 0.05). Conclusion Ebselen can reduce proteinuria, and its mechanism may be related to the reduction of oxidative stress in the kidneys of db / db mice.