去铁酮对糖尿病大鼠肾小管间质的抗氧化作用

The Anti-oxidative Effect of Deferiprone on Renal Tubulointerstitial Injury in Diabetic Rats

目的:研究去铁酮对糖尿病大鼠肾小管间质损伤的干预作用。方法:48只wistar雄性大鼠按随机数字表法分为4组。正常组(10只)普通饲料喂养6周后,腹腔注射柠檬酸缓冲液(40 mg/kg),余38只大鼠高糖高脂饲料喂养6周后,腹腔注射链脲佐菌素(STZ)(40 mg/kg)建立糖尿病模型。药物干预组分别给予50 mg/kg,100 mg/kg去铁酮溶液每日1次灌胃,共8周。糖尿病对照组造模后无药物干预。药物干预8周后测定24 h尿总蛋白;取血测定血清铁和铁蛋白;取肾脏做病理检查,并测定肾脏组织丙二醛(MDA)、总超氧化物歧化酶(TSOD)含量。对TGF–β1、NF-κB进行免疫组化分析。结果:(1)50 mg去铁酮干预组和100 mg去铁酮干预组MDA分别为(32.44±10.83)nmol/mg prot和(62.48±18.46)nmol/mg prot、均低于糖尿病组含量(81.7±23.54)nmol/mg prot;TSOD含量50 mg和100 mg去铁酮干预组分别为(146.72±14.61)nmol/mg prot和(253.5±85.39)nmol/mg prot,均高于糖尿病组(114.67±16.48)nmol/mg prot,差异均有统计学意义(P<0.000 1)。(2)尿总蛋白两两比较50 mg干预组和100 mg干预组的水平无差别,其余组间比较差异均有统计学意义(P<0.000 1)。(3)HE染色糖尿病组和去铁酮干预组肾小管间质存在病理损害,电镜结果显示药物干预组病理改变较糖尿病对照组明显减轻。(4)四组免疫组化TGF-β水平不相同(P<0.000 1)。对TSOD和TGF-β1应用spearman相关分析提示有显著的负相关关系(r=-0.761 66,P<0.000 1)。结论:去铁酮通过干预氧化应激反应来减少TGF-β1、NF-κB的表达以减轻糖尿病大鼠肾小管损伤。

Objective：This further study aimed to investigate that deferiprone can protect the renal tubule in diabetic rats. Methods ：According to random number table, four group were divided, i.e. normal control group（ 10 rats）, diabetic group（ 14 rats）, 50 mg/kg deferiprone treated group（ 12 rats） and 100mg/kg deferiprone treated group（ 12 rats）. Control group were fed with normal diet. After fed with high - fat and high - glucose diet 6 weeks, 38 Type2 diabetic rats were deal with Streptozotocin（40 mg/kg） by in- traperitoneal injection. The two deferiprone treated groups were respectively fed with deferiprone 50 mg/kg per day and 100 mg/kg per day for 8weeks. After 8 weeks medicine intervention, proteinuria,serum iron, and serum ferritin were tested. The kidney organizations were taken pathology examination,the TSOD and the MDA in renal cortex were measured. The immunohistochemistry was used to detect the expression of TGF -β1 and NF - κB in renal tissue of 4 groups rats. Results： （ 1 ） The level of MDA in 50 mg/kg group and 100 mg/kg group were respectively （32.44±10.83 ）nmol/mg prot and（62.48±18.46 ）nmoL/mg prot, much more lower than that in the diabetic group （81.7±23.54） nmol/mg prot; and the level of TSOD in 50 mg/kg group and 100 mg/kg group were respectively （ 146.72±14.61 ） nmol/mg prot and（253.5 ±85.39） nmol/mg prot, much more higher than that in the diabetic group （ 114.67 ±16.48 ） nmol/mg prot. The differences were statistical significance （ P 〈0001 ）. （ 2 ） Proteinuria： Significant statistics difference was found in multiple comparison（P 〈0. 000 1 ）, except 50 mg/kg deferiprone treated group and 100 mg/kg deferiprone treated group. （3） HE staining of renal issue indicated that there were pathological damage of renal tubular and interstitial in diabetic group and the two deferiprone treated groups. Electron microscopy results showed that pathological damage of renal tubular and interstitial in def- eriprone treated group was alleviated. （4）The expression of TGF - βl in four groups were not same （P 〈0. 000 1 ）. The result of Spearman correlation analysis indicated that markedly negative correlation between TSOD and TGF - β1 were presented（ r = - 0. 761 66, P 〈0.000 1 ）. Conclusion： Deferiprone can decrease the expression of TGF - β and NF - KB in renal issue by alleviateing oxidativestress, so it play a role in protecting the renal tubule in diabetic rats.