摘要
目的:探讨丹参酮ⅡA磺酸钠(TSN)对糖尿病大鼠肾脏沉默信息调节因子2的哺乳动物同源体1(SIRT1)和叉头转录因子(Fox01)蛋白影响。方法:采用单次腹腔注射链脲佐菌素(65mg/kg)建立糖尿病大鼠模型,随机分为正常对照组、糖尿病模型组、丹参酮ⅡA磺酸钠组(10mg/kg、20mg/kg)腹腔注射给药。检测第4w、8w、12w时24h尿蛋白排泄率,12w时处死大鼠测定血糖、血总胆固醇、血肌酐,计算肾重/体重比值。检测大鼠血浆中内皮素(ET)、血栓素(TXB2)、6-酮-前列腺素F1α(6-keto-PGF1α)的变化。取肾脏组织测定大鼠SOD活性、GSH-Px活性、MDA含量作为肾脏局部氧化应激状态的检测指标。Western Blot检测大鼠肾脏中SIRT1和Fox01蛋白表达。结果:丹参酮ⅡA磺酸钠(10mg/kg)干预后降低血总胆固醇和血肌酐,还可使糖尿病大鼠尿蛋白排泄量减少,肾重/体重比值降低。丹参酮ⅡA磺酸钠(10mg/kg)干预后血浆ET、TXB2水平明显下降,血浆6-keto-PGF1α水平明显升高,并能有效抑制糖尿病大鼠肾脏氧化应激反应。糖尿病组大鼠肾皮质SIRT1蛋白表达明显下降,乙酰化Fox01蛋白增加,丹参酮ⅡA磺酸钠干预能缓解SIRT1蛋白表达下调,并降低乙酰化Fox01蛋白的表达。丹参酮ⅡA磺酸钠(10mg/kg)干预后能显著改善上述指标。结论:丹参酮ⅡA磺酸钠能有效纠正糖尿病大鼠糖代谢、脂质代谢紊乱,改善肾功能,延缓肾小球硬化的进展,具有一定的肾保护作用。其作用可能与丹参酮ⅡA磺酸钠抑制糖尿病大鼠肾脏氧化应激反应,调节SIRT1活性,并抑制肾脏乙酰化Fox01蛋白表达有关。
Objective： To investigate the effect and mechanisms of sodium tanshinone Ⅱ A sulfonic acid（ TSN） on silent mating type information regulation 2 homolog 1（ SIRT1） and Forkhead transcription factor O1（ Fox01） in kidney of diabetic rats. Methods： Diabetes mellitus was induced in male Sprague-Dawley（ SD） rats（ 150 ~ 200mg） by an intraperitoneal in injection（ 65 mg / kg） of streptozotocin. Periodically,urine albumen / creatinine value（ A / V） was observed in the rats at week 4,8 and 12 respectively as renal function index. Experimental diabetic rats were administered with TSN for 12 weeks,body weight,blood glucose,plasma cholesterol and creatinine levels were measured as clinical and biochemical parameters; Profile of kidney hypertrophy（ KW / BW）. The contents of Endothlin,Thromboxane B2,6-keto-prostaglandin F1α were measured. Kidney homogenate were collected for determination of renal intrinsic anti-oxidant enzyme activities,lipid peroxide（ MDA） levels by chromatometry as oxidative stress indies. The expression of SIRT1 and Fox O1 protein were examined by Western blot. Results： TSN treatment had significant effects on body weight,blood glucose,plasma cholesterol levels of diabetic rats,especially in TSN treatment II. TSN treatment can reduce urinary protein excretion. A / V value was significantly reduced in TSN-treatment group,compared with model groups. TSN treatment decreased kidney weight / body weight ration. The content ET and TXB2 levels of in th blood of TSN treatment rats were significantly decreased,while the content level of 6-keto-PGF1α was increased. DN group significantly downregulated protein expression of SIRTl,whereas it upregulated the protein expression of acetylate Fox01. TSN dramatically inhibited diabetes-induced overexpression of Fox01 and restored the decrease of SIRT1 expression in diabetic rats. Conclusion： TSN treatment can ameliorate the disorders of glucose and lipid metabolism,improve renal function and delay the progression of glomeruloscl
出处
《中药药理与临床》
CAS
CSCD
北大核心
2015年第1期47-50,共4页
Pharmacology and Clinics of Chinese Materia Medica
基金
湖北省自然科学基金(2011CDB315)
教育厅中青年人才项目资助(Q20112803
2012G376)
湖北科技学院培育项目(PY1007)
湖北科技学院糖尿病专项基金(ZX1303)
关键词
丹参酮ⅡA磺酸钠
糖尿病肾病
内皮素
沉默信息调节因子2的哺乳动物同源体
叉头转录因子
Sodium tanshinone IIA sulfonic acid（ 丹参酮ⅡA 磺酸钠
diabetic nephropathy
Endothlin
silent mating type informationregulation 2 homolog 1
Forkhead transcription factor 01
