中华病理学杂志
中華病理學雜誌
중화병이학잡지
Chinese Journal of Pathology
2012年
2期
107-111
,共5页
江警予%黄晓东%王奕%邓艾平%周建华
江警予%黃曉東%王奕%鄧艾平%週建華
강경여%황효동%왕혁%산애평%주건화
肾小球肾炎,膜增生性%转化生长因子β%细胞外基质
腎小毬腎炎,膜增生性%轉化生長因子β%細胞外基質
신소구신염,막증생성%전화생장인자β%세포외기질
Glomerulonephritis,membranoproliferative%Transforming growth factor beta%Extracellular matrix
目的 观察并探讨FTY720是否通过抑制转化生长因子β1-结缔组织生长因子(TGFβ1-CTGF)途径在体内发挥抑制大鼠系膜增生和系膜基质扩张的作用.方法 制备大鼠抗Thy-1系膜增生性肾炎模型,同时给予FTY720干预,观察3组大鼠24 h尿蛋白定量、肾小球系膜增生程度,并分离肾小球进行培养,检测培养上清细胞外基质纤维连接蛋白、层黏蛋白和Ⅳ型胶原蛋白分泌水平变化,即时定量聚合酶链反应(RT-PCR)检测肾小球TGFβ1和CTGF基因表达,Western blot检测肾小球TGFβ1和CTGF蛋白表达.结果 在注射抗体后第1、3、7天,模型组尿蛋白[(27.9±7.3)、(63.5±18.8)、(52.4±15.4) mg/d]较对照组[(8.4±2.4)、(8.4±2.1)、(10.4±3.2)mg/d]明显增多,差异均有统计学意义(均P＜0.01).FTY720干预组第3、7天尿蛋白[(31.4±7.0)、(25.5±7.7)mg/d]与模型组相比明显减少,但仍显著高于对照组,各组间差异有统计学意义(均P＜0.01).注射后第3、7天,FTY720可以显著减少TGFβ1和CTGF基因以及蛋白表达,减低肾小球细胞外基质蛋白分泌,减轻肾小球系膜增生程度.结论 FTY720可以通过抑制TGFβl-CTGF途径显著减轻模型大鼠系膜增生和系膜基质扩张,干预抗Thy-1系膜增生性肾炎的发生.
目的 觀察併探討FTY720是否通過抑製轉化生長因子β1-結締組織生長因子(TGFβ1-CTGF)途徑在體內髮揮抑製大鼠繫膜增生和繫膜基質擴張的作用.方法 製備大鼠抗Thy-1繫膜增生性腎炎模型,同時給予FTY720榦預,觀察3組大鼠24 h尿蛋白定量、腎小毬繫膜增生程度,併分離腎小毬進行培養,檢測培養上清細胞外基質纖維連接蛋白、層黏蛋白和Ⅳ型膠原蛋白分泌水平變化,即時定量聚閤酶鏈反應(RT-PCR)檢測腎小毬TGFβ1和CTGF基因錶達,Western blot檢測腎小毬TGFβ1和CTGF蛋白錶達.結果 在註射抗體後第1、3、7天,模型組尿蛋白[(27.9±7.3)、(63.5±18.8)、(52.4±15.4) mg/d]較對照組[(8.4±2.4)、(8.4±2.1)、(10.4±3.2)mg/d]明顯增多,差異均有統計學意義(均P＜0.01).FTY720榦預組第3、7天尿蛋白[(31.4±7.0)、(25.5±7.7)mg/d]與模型組相比明顯減少,但仍顯著高于對照組,各組間差異有統計學意義(均P＜0.01).註射後第3、7天,FTY720可以顯著減少TGFβ1和CTGF基因以及蛋白錶達,減低腎小毬細胞外基質蛋白分泌,減輕腎小毬繫膜增生程度.結論 FTY720可以通過抑製TGFβl-CTGF途徑顯著減輕模型大鼠繫膜增生和繫膜基質擴張,榦預抗Thy-1繫膜增生性腎炎的髮生.
목적 관찰병탐토FTY720시부통과억제전화생장인자β1-결체조직생장인자(TGFβ1-CTGF)도경재체내발휘억제대서계막증생화계막기질확장적작용.방법 제비대서항Thy-1계막증생성신염모형,동시급여FTY720간예,관찰3조대서24 h뇨단백정량、신소구계막증생정도,병분리신소구진행배양,검측배양상청세포외기질섬유련접단백、층점단백화Ⅳ형효원단백분비수평변화,즉시정량취합매련반응(RT-PCR)검측신소구TGFβ1화CTGF기인표체,Western blot검측신소구TGFβ1화CTGF단백표체.결과 재주사항체후제1、3、7천,모형조뇨단백[(27.9±7.3)、(63.5±18.8)、(52.4±15.4) mg/d]교대조조[(8.4±2.4)、(8.4±2.1)、(10.4±3.2)mg/d]명현증다,차이균유통계학의의(균P＜0.01).FTY720간예조제3、7천뇨단백[(31.4±7.0)、(25.5±7.7)mg/d]여모형조상비명현감소,단잉현저고우대조조,각조간차이유통계학의의(균P＜0.01).주사후제3、7천,FTY720가이현저감소TGFβ1화CTGF기인이급단백표체,감저신소구세포외기질단백분비,감경신소구계막증생정도.결론 FTY720가이통과억제TGFβl-CTGF도경현저감경모형대서계막증생화계막기질확장,간예항Thy-1계막증생성신염적발생.
Objective To investigate whether FTY720 inhibits rat mesangial proliferation and extracellular matrix expansion through suppression of transforming growth factor β1-connective tissue growth factor (TGFβ1-CTGF) pathway,and to explore experimental evidence for its effect on mesangial proliferative glomerulonephritis.Methods A rat model of anti-Thy-1 mesangial proliferative glomerulonephritis was established and FTY720 intervention was performed. Periphery blood lymphocyte count,urine protein excretion,glomerular mesangial proliferation,protein and gene expression of TGFβ1 and CTGF and extracellular matrix protein including fibronectin,laminin and collagen IV in isolated glomeruli were documented at 1,3 and 7 days after injection of anti-Thy-1 antibody.Results The model group developed proteinuria at 1,3 and 7 days after injection of anti-Thy-1 antibody,which were significantly higher [(27.9 ± 7.3 ),(63.5 ± 18.8 ) and ( 52.4 ± 15.4 ) mg/d,respectively] than those in the control group [( 8.4 ± 2.4),( 8.4 ± 2.1 ) and ( 10.4 ± 3.2) mg/d ; respectively,P ＜ 0.01].FTY720 intervention group showed significantly decreased proteinuria at 3 and 7 days after injection [( 31.4 ± 7.0),( 25.5 ± 7.7 )mg/d,respectively] than model group (P ＜ 0.01 ),although higher than the control group (P ＜ 0.01 ).After intervention for 3 and 7 days,FTY720 significantly down-regulated both TGFβ1 and CTGF gene and protein expression in cultured glomeruli,and suppressed the production of glomerular extracellular matrix protein secretion,leading to attenuated mesangial cell proliferation and extracellular matrix expansion in rat anti-Thy-1 mesangial proliferative glonerulonephritis. Conclusion FTY720 significantly attenuates mesangial proliferation and extracellular matrix expansion through inhibition of TGFβ1 -CTGF pathway in rat,and thus ameliorates the development of anti-Thy-1 mesangial proliferative glomerulonephritis.
