丹参酮ⅡA对糖尿病肾病大鼠肾组织TGF-β1/NF-κBp65表达的影响  

Effect of Tanshinone ⅡA on Renal Tumor Growth Factor-beta 1 and Nuclear Factor-kappa B in Diabetic Nephropathy Rats

作　　者：陈刚毅[1] 汤水福[1] 苏保林[1] 李强[1] 林莹莹[2] 李显红[1] 洪钦国[1] 

机构地区：[1]广州中医药大学第一附属医院,广东广州510405 [2]广东省第二中医院,广东广州510405

出　　处：《广州中医药大学学报》2015年第5期891-895,974,共6页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：广东省自然科学基金项目(编号:S2013010011916);广东省医学科研基金项目(编号:A2013233)

摘　　要：【目的】观察活血中药丹参有效成分丹参酮ⅡA对糖尿病肾病(DN)大鼠肾组织转化生长因子-β1(transforming growth factor-1,TGF-β1)和核转录因子-κB(nuclear factor transcription factor-κB,NF-κB)p65 m RNA及相应蛋白的影响,探讨其对DN的防治作用及机制。【方法】选用SD大鼠应用链脲佐菌素(STZ,剂量为40 mg/kg)诱导复制DN大鼠模型。将大鼠随机分为正常组、模型组、丹参酮ⅡA组(剂量为10 mg·kg-1·d-1),各组按相应剂量肌肉注射,于第30后观察各组大鼠体质量、饮水量、24h尿蛋白定量、空腹血糖(Glu)、血肌酐(Cr)、尿素氮(Bun)、总蛋白(TP)、白蛋白(Alb)水平;病理切片采用过碘酸雪夫氏染色(Schiff periodic acid staining,PAS)观察肾组织病理改变;采用Real-time PCR法测定各组大鼠肾组织TGF-β1、NF-κB p65 m RNA的表达,应用免疫印迹(Western blot)技术检测TGF-β1及NF-κB p65蛋白表达。【结果】与正常组比较,模型组大鼠体质量显著下降,饮水量及24 h尿蛋白定量显著增多,血清Glu、Cr、Bun水平显著升高,TP、ALB水平显著下降,肾组织出现病理损害,肾组织的TGF-β1、NF-κB p65 m RNA及蛋白表达显著增加(P<0.05或P<0.01);与模型组比较,丹参酮ⅡA组饮水量下降,24 h尿蛋白定量显著减少,血清Glu、Cr、Bun水平显著下降,TP、ALB水平显著上升,肾组织病理损害减轻,肾组织的TGF-β1、NF-κB p65 m RNA及蛋白表达显著减少(P<0.05或P<0.01)。【结论】丹参酮ⅡA可能通过抑制TGF-β1及NF-κB p65的表达,对肾组织发挥保护作用。Objective To observe the effect of tanshinone ⅡA on renal transforming growth factor beta 1 （TGF-β1） and nuclear factor-kappa B （NF-κB） p65 mRNA and protein expression in diabetic nephropathy （DN） rats, thus to evaluate the therapeutic effect and mechanism of tanshinone ⅡA. Methods SD rats were used as the experimental animal. DN rat model was induced with 40 mg/kg of streptozocin （ STZ） . The rats were randomized into normal group, model group, and tanshinone ⅡA （ 10 mg·kg^ -1·d^ -1, im） group. On the experimental day 30, we examined the body weight, water in-take volume, 24-hour urine protein, fasting glucose （ Glu） , serum creatinine （ Cr） , blood urea nitrogen （ BUN） , total protein （ TP） and albumin （ Alb）. Renal slices after periodic acid Schiff staining （ PAS） were used for the observation of renal pathology. Semi-quantitative reverse transcription polymerase chain reaction （ RT-PCR） was used for the detection of renal TGF-β1 and NF-κB p65 mRNA expression, and Western blotting method was used for the measurement of TGF-β1 and NF-κB p65 protein expression in rats of different groups. Results Compared with the normal group, body weight was decreased, water in-take volume and 24-hour urine protein were increased, serum Glu, Cr, and BUN levels were elevated, TP and Alb levels were decreased, renal pathological damage occurred, and renal TGF-β1 and NF-κB p65 mRNA and protein expressin were promoted in the model group （P〈0.05 or P〈0.01）. Tanshinone ⅡA group had an effect on decreasing water in-take volume, 24-hour urine protein, serum levels of Glu, Cr and Bun, increasing TP and Alb levels, relieving renal pathological damage, and reducing the protein and mRNA expression of renal TGF-β1 and NF-κB p65 （ P〈0.05 or P〈0.01 compared with the model group）. Conclusion Tanshinone ⅡA has protective effect on kidney probably through inhibiting renal TGF-β1 and NF-κB p65 expression in DN rats.

关 键 词：糖尿病肾病/中药疗法 丹参酮ⅡA/药理学 基因表达调控 蛋白表达 肾/病理学 疾病模型 动物 大鼠 

分 类 号：R285.5[医药卫生—中药学]