摘要
目的:探讨槲皮素(QE)对糖尿病肾病(DN)大鼠氧化应激及转化生长因子-β1(TGF-β1)/结缔组织生长因子(CTGF)信号通路的影响。方法:腹腔注射链脲佐菌素(STZ)诱导糖尿病模型,模型成功后随机分为3组:糖尿病肾病组(DN组),槲皮素治疗组(QE组,100 mg·kg-1·d-1),卡托普利阳性对照组(CAP组,10 mg·kg-1·d-1)。另设正常对照组(NS组)。治疗12周,观察治疗期间及治疗后大鼠一般状况、血糖、24 h尿白蛋白、肾脏指数、肌酐、尿素氮,测定血清中总抗氧能力(T-AOC)、总超氧化物歧化酶(T-SOD)、丙二醛(MDA)、还原性谷胱甘肽(GSH)的水平;免疫组化方法观察肾皮质中CTGF的表达水平;RT-PCR方法检测肾皮质中TGF-β1mRNA的相对含量;透射电镜观察肾脏超微结构的变化。结果:造模3组均出现糖尿病及肾脏损害,与DN组相比,槲皮素组大鼠血糖、尿白蛋白、肌酐和尿素氮水平明显降低(P<0.01);T-AOC,T-SOD,GSH活性显著提高、MDA水平明显降低(P<0.05,P<0.01);肾皮质CTGF的表达明显减少(P<0.01);肾皮质中TGF-β1mRNA的相对含量明显降低(P<0.01);电镜显示:与DN相比,槲皮素组大鼠系膜细胞增生程度减轻,基底膜厚度均匀,足突融合减轻。结论:槲皮素可提高DN大鼠的抗氧化水平、抑制肾皮质TGF-β1/CTGF的表达,对DN具有防治作用。
OBJECTIVE To investigate the inhibitory effects of quercetin （QE） on oxidative stress and transforming growth facto-betal （TGF-β1 ）/ connective tissue growth factor （CTGF） in diabetic nephropathic （DN） rats. METHODS After an early DN model was induced by streptozotocin（STZ）, the rats were divided into there groups randomly： diabetic nephropathic group （DN group）, diabetes treated with quercetin group （QE group, 100 mgo kg^-1·d^-1） and diabetes treated with captopril group（CAP group, 10 mg·kg^-1·d^-1）. Some normal other rats were used as normal group. All rats were treated with corre- sponding drugs for 12 weeks. During and after the treatment the general state, blood glucose levels, total urinary protein of the 24 h, kidney index, serum creatinine and blood urea nitrogen, the activities of T-SOD, T-AOC, GSH and MDA levels in ser um were measured by different methods. At the same time, the expression of CTGF and the relative quantities of TGF-β1 mR NA were measured by immunohistochemistry and RT-PCR, respectively. RESULTS Diabetes mellitus and renal lesions oc curred in the three model groups. Compared with DN group, fasting blood glucose, creatinine （Cr）, blood urea nitrogen （BUN） ,and urine protein in QE rats were ssignificantly lower（P〈0. 01）; the activities of T-SOD, T-AOC, GSH were in- creased but MDA levels were significantly reduced（P〈0. 05,P〈0. 01） ; In addition, the expression of CTGF and the relative quantities of TGF-β1 mRNA were significantly decreased（P〈0. 01 ）. CONCLUSION The results suggest that quercetin may improve several pharmacological targets in the progress of DN and is a potential drug for the prevention of early DN.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2012年第13期1012-1016,共5页
Chinese Journal of Hospital Pharmacy
基金
江苏省自然科学基金(编号:BK2011211)
徐州市科技计划项目(编号:XF10C074
XX10A068)
徐州医学院院长专项人才基金(编号:2010KJZ25)
