| 摘要: |
| [目的] 研究复方血栓通胶囊对糖尿病肾病(DN)大鼠24 h尿白蛋白、尿肌酐、血肌酐和血尿素氮等相关代谢指标的影响,及应用基因芯片探讨复方血栓通胶囊改善DN 大鼠肾功能的机制。[方法] 选用SD 大鼠45 只,高脂喂养/ 链尿佐菌素(STZ)注射法制备DN 模型,将DN 成模大鼠40 只随机分为小剂量、中剂量、大剂量血栓通组[ 分别给予0.3、0.6、1.2 g/(kg·d)的血栓通粉末悬浊液]、DN 模型组(给予生理盐水)。另外选用SD 大鼠10 只为正常对照组(给予生理盐水),均连续灌胃12 周。每月末测定大鼠空腹血糖(FBG)和体质量。3 个月末测定大鼠24 h尿白蛋白、尿肌酐、血肌酐和血清尿素氮水平。取大鼠肾脏组织进行Illumina基因芯片实验以期从整体基因角度揭示复方血栓通胶囊改善肾功能的机制。实时定量PCR 实验验证基因芯片的结果。[结果] 复方血栓通胶囊能以剂量依赖的方式降低24 h尿白蛋白、血肌酐和血清尿素氮,升高尿肌酐(P<0.05或P<0.01)。基因芯片显示大剂量血栓通组较模型组有67 个基因显著改变,其中34 个上调,33 个下调。实时定量PCR 实验发现大剂量血栓通组胶原蛋白1 型1(Col1a1)、结缔组织生长因子(Ctgf)和转化生长因子1(Tgfb1)基因较模型组显著下调,细胞色素P450 家族2 亚族C 肽23(Cyp2c23)和Nephrin-1(Nphs1)显著上调。[结论] 复方血栓通胶囊能有效改善DN 大鼠肾脏功能,其机制可能涉及Bmp2-Tgfβ-Ctgf通路,Cyp2c23 和足细胞损伤修复。 |
| 关键词: 复方血栓通胶囊 基因芯片 糖尿病肾病 足细胞 |
| DOI：10.11656/j.issn.1672-1519.2015.06.11 |
| 分类号: |
| 基金项目:北京协和医院基金项目(2006119);国家临床重点专科建设项目(宰月再在圆园员员原愿苑猿);国家自然科学基金项目(81170736,81300649);中华医学会临床医学科研专项基金-默沙东糖尿病研究项目(12030450345);北京协和医院中青年基金,协和青年基金(33320140022);中央高校基本科研业务费专项基金。 |
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| Study of the mechanism of Fufang Xueshuantong capsule on kidney function |
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ZHANG Qian, XIAO Xin-hua, LI Ming, LI Wen-hui, YU Miao, ZHANG Hua-bing, PING Fan, YANG Guo-hua
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Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
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| Abstract: |
| [Objective] To explore the effects of Fufang Xueshuantong capsule(FXST) on the kidney function in diabetic nephropathy (DN) rats and to investigate its possible mechanism. [Methods] SD rats were fed with high fat diet and injected with STZ to make diabetic nephropathy(DN) model. DN rats were randomly divided into four groups: low dose (XSTL), medium dose(XSTM), high dose(XSTH) FXST groups(treated with 0.3, 0.6, 1.2 g/kg/d FXST, respectively, n=10), and DN model group(treated with saline, n=10). Normal rats were enrolled as normal group(treated with saline, n=10). The fasting blood glucose, weight, 24-h urinary albumin, urinary creatinine, blood creatinine and blood urea nitrogen were tested. Illumina Rat Ref-12 Expression BeadChip gene array experiment was done using kidney of rats. [Results] FXST could reduce 24-h urinary albumin, serum creatinine and serum urea nitrogen, and increase urinary creatinine in a dose dependent manner compared with those of DN model group(P<0.05 or P<0.01). Gene array showed that FXST significantly changed expression of genes(34 increased, 33 decreased). Real-time PCR showed that relative levels for Col1a1, Ctgf and Tgfb1 were significantly decreased in FXST group, compared with the model group. Cyp2c23 and Nphs1 were increased. [Conclusion] FXST can moderate the kidney function in DN rats. The mechanism may be involved with BMP2-TGFβ-CTGF pathway, CYP2C23 and podocytes proteins. |
| Key words: Fufang Xueshuantong capsule gene array diabetic nephrapathy podocyte |
