基于p38 MAPK/PPAR-γ通路研究车前草水提物对糖尿病肾病大鼠纤维化的影响
摘要
目的:探究车前草水提物对糖尿病肾病(DN)大鼠肾纤维化及p38丝裂原活化蛋白激酶(p38 MAPK)/过氧化物酶体增殖物激活受体-γ(PPAR-γ)通路的影响。方法:120只大鼠中抽取12只作为对照组,其余建立DN大鼠模型,取造模成功60只大鼠,随机分为模型组、阳性药物组(缬沙坦组,4. 8×10-3g/kg)及车前草水提物低(1. 17 g/kg)、中(2. 34 g/kg)、高(4. 68 g/kg)剂量组。给药后12周,观察大鼠病理变化及肾组织各项指标变化情况。结果:HE染色发现,模型组大鼠肾小管上皮细胞有空泡出现且萎缩,肾小球体积变大,系膜基质显著增加;车前草干预后肾脏病变情况明显减轻。车前草各干预组大鼠血清SCr、BUN、24 h UTP含量及Cys C、TIMP-1、TGF-β1、ColⅣ水平随浓度升高而降低(P <0. 05)。模型组、车前草各干预组和缬沙坦组血清CysC、TIMP-1、TGF-β1及ColⅣ水平较对照组升高(P <0. 05)。各组大鼠肾组织比较差异有统计学意义(P <0. 05),随着车前草水提物给药浓度的升高,肾组织p-p38 MAPK水平逐渐降低,PPAR-γ水平逐渐升高。结论:车前草水提物能明显减轻DN大鼠的肾脏损伤程度,其机制可能与p38 MAPK通路受到抑制及PPAR-γ通路被激活有关。
引文
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12 . Hou X,Tian J,Geng J,et al. MicroRNA-27a promotes renal tubulointerstitial fibrosis via suppressing PPARγpathway in diabetic nephropathy. Oncotarget,2016,7(30):47760-47776.
13 . Liu Y,Jia L,Liu ZC,et al. Emodin ameliorates high-glucose induced mesangial p38 over-activation and hypocontractility via activation of PPARγ. Experimental&Molecular Medicine,2009,41(9):648.
2 .钟凌,冯韵霖,杨鸿玲,等. miR-451a在糖尿病肾病肾纤维化中的临床应用研究.现代预防医学,2017,44(5):941-946.
3 .宋芊,相田园,许建梅,等.冬连胶囊对STZ诱导糖尿病肾病大鼠p38MAPK、CREB1及TGFβ1蛋白表达的影响.中医药信息,2016,33(1):1-5.
4 . Wang T,Chen SS,Chen R,et al. Reduced beta 2 glycoprotein I improves diabetic nephropathy via inhibiting TGF-β1-p38MAPK pathway. International Journal of Clinical&Experimental Pathology,2015,8(3):2321-2333.
5 . Zhou Z,Wan J,Hou X,et al. MicroRNA-27a promotes podocyte injury via PPARγ-mediatedβ-catenin activation in diabetic nephropathy. Cell Death&Disease,2017,8(3):e2658.
6 .陈兰英,王昌芹,罗园红,等.车前草水提物对肾小球肾炎大鼠的保护作用研究.时珍国医国药,2015,26(12):2874-2877.
7 .倪伟建,丁海华,唐丽琴,等.小檗碱对糖尿病肾病大鼠肾组织VEGF表达的影响.中国药理学通报,2015,31(6):795-800.
8 . Marchant V,Droguett A,Valderrama G,et al. Tubular overexpression of Gremlin in transgenic mice aggravates renal damage in diabetic nephropathy. American Journal of Physiology Renal Physiology,2015,309(6):F559-F568.
9 .李书瑞,张绍义,关连颖,等.黄芪注射液对糖尿病对比剂肾病大鼠肾功能作用的研究.中国中西医结合肾病杂志,2017,18(2):138-140,190.
10 . Chen J,Cui W,Zhang Q,et al. Low molecular weight fucoidan ameliorates diabetic nephropathy via inhibiting epithelial-mesenchymal transition and fibrotic processes. American Journal of Translational Research,2015,7(9):1553-1563.
11 . Peng L,Li J,Xu Y,et al. The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats. International Journal of Endocrinology,2016,2016(4):1690474.
12 . Hou X,Tian J,Geng J,et al. MicroRNA-27a promotes renal tubulointerstitial fibrosis via suppressing PPARγpathway in diabetic nephropathy. Oncotarget,2016,7(30):47760-47776.
13 . Liu Y,Jia L,Liu ZC,et al. Emodin ameliorates high-glucose induced mesangial p38 over-activation and hypocontractility via activation of PPARγ. Experimental&Molecular Medicine,2009,41(9):648.