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西格列汀延缓或阻止2型糖尿病肾病进展的实验研究 被引量:27

Experimental study of sitagliptin on the delay or stop of the progress of type 2 nephropathy
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摘要 目的探讨西格列汀(SIT)延缓或阻止2型糖尿病肾病(DN)进展的作用及其可能机制。方法高脂饲养加小剂量链脲佐菌素诱导建立大鼠DN模型,成模后,随机分为模型组(DN组)和西格列汀组(SIT组),同时设立对照组(NC组)。连续灌胃12周后,取肾组织进行Masson染色检测肾纤维化程度,用反转录PCR法检测肾组织中Toll样受体2(TLR2)、TLR4、核转录因子-κB(NF-κB)mRNA的表达,用免疫组化法检测肾组织中TLR2、TLR4蛋白的含量,用Western blotting法检测肾组织中NF-κB蛋白的含量。结果与NC组相比,DN组的肾纤维化程度、TLR2、TLR4、NF-κB的表达均显著增加(P<0.01)。与DN组相比,SIT组的肾纤维化程度、TLR2、TLR4、NF-κB的表达均有所降低(P<0.05)。结论西格列汀可改善2型糖尿病大鼠的肾纤维,其机制可能与抑制TLR2、TLR4/NF-κB通路的过度活化有关。 Objective To study the derect action and part possible mechanism of sitagliptin( SIT) on the delay or stop of the progress of type 2 diabetic nephropathy( DN). Methods The rats were randomly divided into normal group( NC group),diabetic nephropathy group( DN group) and sitagliptin treatment group( SIT group). The type 2 diabetes mellitus rats were induced by a high fat diet and repeated low dose streptozocin injections. At the end of the 12^(th) week in treatment,Masson staining was used to observe the renal fibrosis. RT-PCR was used to detect the mRNA levels of Toll-like-receptor 2( TLR2),TLR4,nuclear factor-κB( NF-κB). Immunohistochemical method was used to detect the content of TLR2 and TLR4. Western blotting was used to detect the content of NF-κB. Results Compared with NC group,the degree of renal fibrosis,and the expressions of TLR2,TLR4,NF-κB of DN group significantly increased( P〈0. 01). However,compared with DN group,the degree of renal fibrosis,and the expressions of TLR2,TLR4,NF-κB of SIT-treated rats significantly decreased( P〈0. 05).Conclusion SIT can prevent the renal fibrosis by down-regulating the expression of TLR2,TLR4 / NF-κB pathway.
出处 《中国临床药理学杂志》 CAS CSCD 北大核心 2016年第1期45-47,54,共4页 The Chinese Journal of Clinical Pharmacology
基金 国家级大学生创新训练项目基金资助项目(201410313024) 江苏省高等学校大学生创新创业训练计划基金资助项目(201410313024Z) 徐州医学院药学院研究生科研创新计划项目基金资助项目(2014YKYCX013)
关键词 西格列汀 2型糖尿病肾病 Toll样受体2、4/核转录因子-κB通路 sitagliptin type 2 diabetic nephropathy Toll-like-receptor 2 4 / nuclear factor-κB pathway
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