CAJ | 학술논문

目的研究血管紧张素1-7(Ang1-7)对糖尿病大鼠肾小管间质纤维化的影响及其可能机制.方法 32只雄性Wistar大鼠被随机分为4组:健康对照组(NC组)、模型组(DM组)、替米沙坦组(TM组)、治疗组(T组).建模成功后第9周末检测各组大鼠24 h尿蛋白量、尿NAG/Cr、血糖、血胰岛素、三酰甘油(TG)、总胆固醇(TC)、BUN、Scr、血K+及血Na+ ;PAS染色观察肾脏病理改变 ;实时定量PCR法检测各组大鼠肾脏组织中转化生长因子β1(TGF-β1)、过氧化物酶体增殖物激活受体(PPAR)γ、α平滑肌肌动蛋白(α-SMA)mRNA水平 ;Western印迹法检测PPARγ、α-SMA、TGF-β1蛋白表达.结果 (1)第9周末,DM组大鼠血压、尿蛋白量、肾质量/体质量较NC组显著升高(P＜0.05),TM组及T组较DM组显著降低(P＜0.05),且T组变化更明显.(2)DM组第9周末肾间质损伤指数显著高于NC组(P＜0.05),TM组及T组则低于DM组(P＜0.05).(3)实时定量PCR结果显示,DM组TGF-β1、α-SMAmRNA水平显著升高(P＜0.05),PPARγ mRNA水平显著下降(P＜0.05),TM组及T组较DM组TGF-β1、α-SMA mRNA水平均显著下降(P＜0.05),PPARγ mRNA水平显著上升(P＜0.05),且T组变化更明显.(4)Western印迹结果显示,DM组TGF-β1、α-SMA蛋白水平显著升高(P＜0.05),PPARγ蛋白水平显著下降(P＜0.05),TM组及T组较DM组TGF-β1、α-SMA蛋白水平均显著下降(P＜0.05),PPARγ蛋白水平显著上升(P＜0.05),且T组变化更明显.结论 Ang1-7在体内可通过上调PPARγ表达,抑制α-SMA表达,对糖尿病大鼠肾小管间质纤维化可能具有抑制作用.
목적 연구혈관긴장소1-7(Ang1-7)대당뇨병대서신소관간질섬유화적영향급기가능궤제.방법 32지웅성Wistar대서피수궤분위4조:건강대조조(NC조)、모형조(DM조)、체미사탄조(TM조)、치료조(T조).건모성공후제9주말검측각조대서24 h뇨단백량、뇨NAG/Cr、혈당、혈이도소、삼선감유(TG)、총담고순(TC)、BUN、Scr、혈K+급혈Na+ ;PAS염색관찰신장병리개변 ;실시정량PCR법검측각조대서신장조직중전화생장인자β1(TGF-β1)、과양화물매체증식물격활수체(PPAR)γ、α평활기기동단백(α-SMA)mRNA수평 ;Western인적법검측PPARγ、α-SMA、TGF-β1단백표체.결과 (1)제9주말,DM조대서혈압、뇨단백량、신질량/체질량교NC조현저승고(P＜0.05),TM조급T조교DM조현저강저(P＜0.05),차T조변화경명현.(2)DM조제9주말신간질손상지수현저고우NC조(P＜0.05),TM조급T조칙저우DM조(P＜0.05).(3)실시정량PCR결과현시,DM조TGF-β1、α-SMAmRNA수평현저승고(P＜0.05),PPARγ mRNA수평현저하강(P＜0.05),TM조급T조교DM조TGF-β1、α-SMA mRNA수평균현저하강(P＜0.05),PPARγ mRNA수평현저상승(P＜0.05),차T조변화경명현.(4)Western인적결과현시,DM조TGF-β1、α-SMA단백수평현저승고(P＜0.05),PPARγ단백수평현저하강(P＜0.05),TM조급T조교DM조TGF-β1、α-SMA단백수평균현저하강(P＜0.05),PPARγ단백수평현저상승(P＜0.05),차T조변화경명현.결론 Ang1-7재체내가통과상조PPARγ표체,억제α-SMA표체,대당뇨병대서신소관간질섬유화가능구유억제작용.
Objective To investigate the effects of angiotensin1-7 (Ang1-7) on renal tubulointerstitial fibrosis of diabetic rats.Methods Thirty-two male Wistar rats were randomly divided into four groups: normal control group,diabetic group,telmisartan group,Ang1-7-treated group.For 9 weeks after diabetes mellitus model established,24 h proteinuria,urine NAG/Cr,glucose,insulin,TG,TC,BUN,Scr,Na+ and K+ were assessed.Renal pathological changes were evaluated by PAS staining; Expression of TGF-β1,PPARγ and α-SMA mRNA was deteeted by real-time PCR; Protein levels of PPARγ,α-SMA and TGF-β1 were detected by Western blotting.Results (1)At the end of the ninth week,the blood pressure,proteinuria,renal weight/body weight in group DM were significantly higher than those in group NC (P＜0.05).(2)Renal interstitial fibrosis in group DM was obviously severe as compared to group NC (P＜0.05),but was improved in group TM and group T(P＜0.05).(3)TGF-β1 and α-SMA mRNA in group DM were significantly increased,and PPARγ mRNA was significantly decreased.Compared with group DM,TGF-β1 and α-SMA mRNA were significantly decreased,and PPARγ mRNA was significantly increased in group TM and group T,especially in group T.(4)TGF-β1 and α-SMA in group DM were significantly increased,and PPARγ decreased significantly.Compared with group DM,TGF-β1 and α-SMA decreased significantly,PPARγ increased significantly in group TM and group T,especially in group T.Conclusion Ang1-7 inhibits high glucose-induced α-SMA expression in vivo through up-regulating the PPAR expression and may inhibit renal tubulointerstitial fibrosis of diabetic rats.