丁羟茴香醚改善糖尿病肾病大鼠泛影葡胺肾损害的研究

目的:研究泛影葡胺(DTZ)对糖尿病肾病模型大鼠肾小管上皮细胞的损害作用,及其对活性氧(ROS)清除剂丁羟茴香醚(BHA)治疗的反应。方法:将25只雄性SD大鼠随机分为3组,对照组10只,糖尿病肾病组10只,BHA组5只。后2组大鼠给予腹腔注射链脲佐菌素制备糖尿病大鼠模型,8周后发展为糖尿病肾病。第9周开始,BHA组开始以BHA50mg/kg.d灌胃直至实验结束。灌胃第4天,从对照组、糖尿病肾病组大鼠中各随机抽取5只,与BHA组5只大鼠一起,一次性尾静脉注射60%DTZ(6ml/kg)。灌胃第7天处死大鼠,观察肾功能、肾脏病理的变化及肾小管上皮细胞凋亡情况,并测定各组大鼠肾组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活力、丙二醛(MDA)含量等生化指标。结果:对照组大鼠中,注射DTZ者血清肌酐较未注射者无明显增加(P>0.05),肾组织SOD、CAT活性、MDA含量虽有所增加,但其差异无统计学意义(P均>0.05)。糖尿病肾病组大鼠中,注射DTZ者血清肌酐较未注射者明显增加(P<0.05),肾组织SOD、CAT活性明显下降,MDA含量增加(P均<0.05)。BHA组大鼠以上改变均显著减轻(P<0.05)。DTZ注射后,糖尿病肾病组大鼠血清肌酐较对照组大鼠明显增高(P<0.05),肾组织SOD、CAT活性明显下降,MDA含量增加(P均<0.05)。组织学检查发现,糖尿病肾病组大鼠注射DTZ后,肾小管上皮细胞空泡变性、刷状缘变薄、大片细胞脱落,TUNEL染色显示肾小管上皮细胞凋亡率明显增加(P<0.05)。在BHA组大鼠肾脏中,以上生化指标及组织学改变均有明显改善。结论:糖尿病肾病状态下,肾脏抗氧化能力低下,导致了肾脏中存在着较强的氧化应激状态;DTZ可通过增加肾脏氧化应激程度导致进一步肾脏损害;使用抗氧化剂阻断氧化应激,能有效抑制DTZ所致的肾损害。

Protective effect of butyl hydroxy anisol against oxidative stress in diabetic rats treated with diatrizoate

Objective：To investigate the effect of butyl hydroxy anisol （BHA） on oxidative stress in diabetic rats treated with diatrizoate. Methods：Twenty-five male sprague-dowley rats were randomly assigned into 3 groups as control group （ n = 10） ,diabetic nephropathy （DN） group （ n = 10） and BHA group （ n = 5）. Rats in the last 2 groups received streptotoein by intraperitoneal injection （60 mg/kg） treatment. After 8 weeks, BHA group rats were treated with BHA （50 mg/kg.d） until they were sacrificed. Diatrizoate was infused intravenous to rats randomly chose from control group, DN group and BHA group （5 rats each group） 3 days later. The animals were sacrificed and kidney tissues and serum samples were collected to investigate the contents of SOD, CAT, MDA in kidney and creatinine in serum. Renal histological analysis and TUNEL assay were also done. Results：Serum creatinine and the levels of SOD, CAT, MDA in kidney did not increase significantly after infused with di- atrizoate in control group rats （ P 〉0.05）. In DN group rats, the serum ereatinine stepped up and SOD, CAT, MDA in kid ney altered dramatically after diatrizoate infusion （ P 〈0.05）, but these alterations ameliorated in BHA group （ P 〈0.05）. The serum ereatinine in DN group was significantly higher than that in control group, SOD, CAT, MDA in kidney decreased and MDA increased more dramatically than that in DN group. Renal histological analysis indicated granulovaeuolar degeneration, brush border thinning and exfoliation in tubular cells, and TUNEL assay demonstrated a significant growth in the apoptotic renal tubular cells in DN group rats （ P 〈0. 05）. Identically, these histological alterations improved after diatrizoate infusion in BHA group rats （ P〈0.05）. Conclusion： Renal antioxidative capacity in diabetic nephropathy is impaired and will be depressed after diatrizoate infusion. BHA can improve the antioxidative capacity and protect against diatrizoate-induced oxidative stress in diabetic nephropathy.