中国医师杂志
中國醫師雜誌
중국의사잡지
JOURNAL OF CHINESE PHYSICIAN
2014年
10期
1322-1327
,共6页
陈丽%李竞%曾姣娥%宁尚侠
陳麗%李競%曾姣娥%寧尚俠
진려%리경%증교아%저상협
茶%酚类/药理学%转化生长因子β%糖尿病肾病%纤维化%疾病模型,动物%小鼠
茶%酚類/藥理學%轉化生長因子β%糖尿病腎病%纖維化%疾病模型,動物%小鼠
다%분류/약이학%전화생장인자β%당뇨병신병%섬유화%질병모형,동물%소서
Tea%Phenols/pharmacology%Transforming growth factor beta%Diabetic nephropathies%Fibrosis%Disease models,animal%Mice
目的 探讨茶多酚(TP)在预防小鼠糖尿病肾纤维化中的作用及可能机制.方法 通过高脂饲养联合链脲霉素(STZ,50 mg/kg)腹腔注射,构建糖尿病肾病肾纤维化小鼠模型,并观察茶多酚的干预作用;采用实时定量PCR或Westernblotting检测组织或细胞中纤维化相关基因的表达.结果 高脂饲养联合STZ腹腔注射诱导的糖尿病肾病模型小鼠具有明显的肾纤维化,并且纤维化肾组织中E-cadherin表达下调,而转化生长因子-β1(TGF-β1)、波形蛋白(Vimentin)、α-平滑肌肌动蛋白(α-SMA)、纤连蛋白(Fibronectin)、Ⅰ型胶原(Collagen Ⅰ)和Ⅳ型胶原(CollagenⅣ)等纤维化相关基因表达上调;茶多酚能明显缓解糖尿病肾病模型小鼠的肾纤维化进程,且上调模型小鼠肾组织中E-cadherin的表达,抑制TGF-β1信号通路靶基因Vimentin、α-SMA、Fibronectin、Collagen Ⅰ和CollagenⅣ等纤维化相关基因的表达;在细胞水平,用TGF-β1处理NRK-52E大鼠肾小管上皮细胞,发现TGF-β1能诱导NRK-52E细胞形态发生纤维性变,并诱导细胞中TGF-β信号通路活化及纤维化相关基因的表达,而茶多酚则可明显抑制TGF-β1对NRK-52细胞纤维性变的诱导作用.结论 茶多酚可能通过抑制TGF-β信号通路缓解糖尿病肾病肾纤维化进程,为糖尿病肾病的临床防治提供重要的实验数据.
目的 探討茶多酚(TP)在預防小鼠糖尿病腎纖維化中的作用及可能機製.方法 通過高脂飼養聯閤鏈脲黴素(STZ,50 mg/kg)腹腔註射,構建糖尿病腎病腎纖維化小鼠模型,併觀察茶多酚的榦預作用;採用實時定量PCR或Westernblotting檢測組織或細胞中纖維化相關基因的錶達.結果 高脂飼養聯閤STZ腹腔註射誘導的糖尿病腎病模型小鼠具有明顯的腎纖維化,併且纖維化腎組織中E-cadherin錶達下調,而轉化生長因子-β1(TGF-β1)、波形蛋白(Vimentin)、α-平滑肌肌動蛋白(α-SMA)、纖連蛋白(Fibronectin)、Ⅰ型膠原(Collagen Ⅰ)和Ⅳ型膠原(CollagenⅣ)等纖維化相關基因錶達上調;茶多酚能明顯緩解糖尿病腎病模型小鼠的腎纖維化進程,且上調模型小鼠腎組織中E-cadherin的錶達,抑製TGF-β1信號通路靶基因Vimentin、α-SMA、Fibronectin、Collagen Ⅰ和CollagenⅣ等纖維化相關基因的錶達;在細胞水平,用TGF-β1處理NRK-52E大鼠腎小管上皮細胞,髮現TGF-β1能誘導NRK-52E細胞形態髮生纖維性變,併誘導細胞中TGF-β信號通路活化及纖維化相關基因的錶達,而茶多酚則可明顯抑製TGF-β1對NRK-52細胞纖維性變的誘導作用.結論 茶多酚可能通過抑製TGF-β信號通路緩解糖尿病腎病腎纖維化進程,為糖尿病腎病的臨床防治提供重要的實驗數據.
목적 탐토다다분(TP)재예방소서당뇨병신섬유화중적작용급가능궤제.방법 통과고지사양연합련뇨매소(STZ,50 mg/kg)복강주사,구건당뇨병신병신섬유화소서모형,병관찰다다분적간예작용;채용실시정량PCR혹Westernblotting검측조직혹세포중섬유화상관기인적표체.결과 고지사양연합STZ복강주사유도적당뇨병신병모형소서구유명현적신섬유화,병차섬유화신조직중E-cadherin표체하조,이전화생장인자-β1(TGF-β1)、파형단백(Vimentin)、α-평활기기동단백(α-SMA)、섬련단백(Fibronectin)、Ⅰ형효원(Collagen Ⅰ)화Ⅳ형효원(CollagenⅣ)등섬유화상관기인표체상조;다다분능명현완해당뇨병신병모형소서적신섬유화진정,차상조모형소서신조직중E-cadherin적표체,억제TGF-β1신호통로파기인Vimentin、α-SMA、Fibronectin、Collagen Ⅰ화CollagenⅣ등섬유화상관기인적표체;재세포수평,용TGF-β1처리NRK-52E대서신소관상피세포,발현TGF-β1능유도NRK-52E세포형태발생섬유성변,병유도세포중TGF-β신호통로활화급섬유화상관기인적표체,이다다분칙가명현억제TGF-β1대NRK-52세포섬유성변적유도작용.결론 다다분가능통과억제TGF-β신호통로완해당뇨병신병신섬유화진정,위당뇨병신병적림상방치제공중요적실험수거.
Objective To investigate the role and its mechanisms of tea polyphenols (TP) in the prevention of diabetic renal fibrosis.Methods Mouse model of diabetes mellitus was induced by high-fat diet combined with intraperitoneal injection of streptozotocin (STZ,50 mg/kg).Real-time quantitative polymerase chain reaction (RT-PCR) and Western blotting were used to determine the transcription and expression of genes related to the renal fibrosis.Results Diabetic mouse model was successfully established by injection of high-fat diet plus STZ.The transcription of E-cadherin was decreased and transcriptions of genes related to the renal fibrosis such as transforming growth factor β1 (TGF-β1),vimentin,α-smooth muscle actin (α-SMA),fibronectin,collagen Ⅰ,and collagen Ⅳ were increased in the renal tissues of diabetic mice,which indicated the diabetic nephropathy with renal fibrosis in diabetic mice.Treatment of diabetic mice with TP for 8 weeks could reverse the process of diabetic nephropathy with renal fibrosis in accompanied with the increase of E-cadherin transcription and decrease of TGF-β1-targeted genes such as vimentin,α-SMA,fibronectin,collagen Ⅰ,and collagen Ⅳ in the renal tissues of diabetic mice.Moreover,incubation of normal rat kidney proximal tubular epithelial cell line (NRK-52E) cells with TGF-β1 could also induce the changes in fibrotic morphological and transcription or expression of fibrosis related genes,and all effects of TGF-β1 could be inhibited by TP treatment in NRK-52E cells.Conclusions These results indicate that chronic treatment with TP may relieve renal fibrosis of diabetic nephropathy through the inhibition of TGF-β signaling pathway and provide important experimental data for the prevention and treatment of diabetic nephropathy.
