中华肾脏病杂志
中華腎髒病雜誌
중화신장병잡지
2012年
1期
47-51
,共5页
沈洁%胡园园%朱艳%唐杰龙%刘帅
瀋潔%鬍園園%硃豔%唐傑龍%劉帥
침길%호완완%주염%당걸룡%류수
糖尿病肾病%纤维化%骨桥蛋白%厄贝沙坦
糖尿病腎病%纖維化%骨橋蛋白%阨貝沙坦
당뇨병신병%섬유화%골교단백%액패사탄
Diabetic nephropathy%Fibrosis%Osteopontin%Irbesartan
目的 探讨不同剂量厄贝沙坦对糖尿病大鼠肾组织骨桥蛋白( OPN)表达及小管间质纤维化的影响.方法 将63只8周龄雄性Wistar大鼠按随机数字表法分为正常对照组(Ctrl组,n=7)、糖尿病组(DM组,n=14)、30 mg/kg肼屈嗪干预组(DM+ Hyd组,n=12)、25mg·kg-1· d-1厄贝沙坦干预组(DM+Irb25组,n=10)、50 mg·kg-1·d-1厄贝沙坦干预组(DM+Irb50组,n=9)和200 mg · kg-1·d-1厄贝沙坦干预组(DM+Irb200组,n=11).糖尿病模型造模成功后4周,灌胃法给予相应剂量的肼屈嗪和厄贝沙坦.第12周末,观察各组大鼠24h尿白蛋白排泄率(UAER)、内生肌酐清除率(Ccr)；PAS及Masson染色观察各组大鼠肾脏病理形态和胶原纤维沉积；ELISA法测定各组大鼠肾组织AngⅡ含量；实时定量PCR检测大鼠肾组织转化生长因子(TGF)β1、OPN mRNA的表达.结果 药物干预各组大鼠UAER、Ccr较DM组显著减少(均P＜ 0.05).DM组大鼠肾小球肥大,系膜基质增生,肾小球及小管间质有大量胶原纤维沉积；药物干预后,肾小球及肾小管上述病变减轻.DM组大鼠肾组织AngⅡ水平及TGF-β1、OPN mRNA表达均显著升高(均P＜0.05),给予肼屈嗪及厄贝沙坦干预后,AngⅡ、TGF-β1、OPN mRNA表达显著降低(均P＜0.05),且随着厄贝沙坦剂量的递增而递减.相关分析结果显示,DM组大鼠肾组织AngⅡ水平与OPN mRNA的表达呈正相关(r=0.74,P＜0.01).结论 厄贝沙坦通过减少肾脏局部AngⅡ水平,进而减少肾脏TGF-β1、OPN mRNA的表达,最终减轻小管间质纤维化,发挥肾脏保护作用,且这种保护作用具有剂量依赖性.
目的 探討不同劑量阨貝沙坦對糖尿病大鼠腎組織骨橋蛋白( OPN)錶達及小管間質纖維化的影響.方法 將63隻8週齡雄性Wistar大鼠按隨機數字錶法分為正常對照組(Ctrl組,n=7)、糖尿病組(DM組,n=14)、30 mg/kg肼屈嗪榦預組(DM+ Hyd組,n=12)、25mg·kg-1· d-1阨貝沙坦榦預組(DM+Irb25組,n=10)、50 mg·kg-1·d-1阨貝沙坦榦預組(DM+Irb50組,n=9)和200 mg · kg-1·d-1阨貝沙坦榦預組(DM+Irb200組,n=11).糖尿病模型造模成功後4週,灌胃法給予相應劑量的肼屈嗪和阨貝沙坦.第12週末,觀察各組大鼠24h尿白蛋白排洩率(UAER)、內生肌酐清除率(Ccr)；PAS及Masson染色觀察各組大鼠腎髒病理形態和膠原纖維沉積；ELISA法測定各組大鼠腎組織AngⅡ含量；實時定量PCR檢測大鼠腎組織轉化生長因子(TGF)β1、OPN mRNA的錶達.結果 藥物榦預各組大鼠UAER、Ccr較DM組顯著減少(均P＜ 0.05).DM組大鼠腎小毬肥大,繫膜基質增生,腎小毬及小管間質有大量膠原纖維沉積；藥物榦預後,腎小毬及腎小管上述病變減輕.DM組大鼠腎組織AngⅡ水平及TGF-β1、OPN mRNA錶達均顯著升高(均P＜0.05),給予肼屈嗪及阨貝沙坦榦預後,AngⅡ、TGF-β1、OPN mRNA錶達顯著降低(均P＜0.05),且隨著阨貝沙坦劑量的遞增而遞減.相關分析結果顯示,DM組大鼠腎組織AngⅡ水平與OPN mRNA的錶達呈正相關(r=0.74,P＜0.01).結論 阨貝沙坦通過減少腎髒跼部AngⅡ水平,進而減少腎髒TGF-β1、OPN mRNA的錶達,最終減輕小管間質纖維化,髮揮腎髒保護作用,且這種保護作用具有劑量依賴性.
목적 탐토불동제량액패사탄대당뇨병대서신조직골교단백( OPN)표체급소관간질섬유화적영향.방법 장63지8주령웅성Wistar대서안수궤수자표법분위정상대조조(Ctrl조,n=7)、당뇨병조(DM조,n=14)、30 mg/kg정굴진간예조(DM+ Hyd조,n=12)、25mg·kg-1· d-1액패사탄간예조(DM+Irb25조,n=10)、50 mg·kg-1·d-1액패사탄간예조(DM+Irb50조,n=9)화200 mg · kg-1·d-1액패사탄간예조(DM+Irb200조,n=11).당뇨병모형조모성공후4주,관위법급여상응제량적정굴진화액패사탄.제12주말,관찰각조대서24h뇨백단백배설솔(UAER)、내생기항청제솔(Ccr)；PAS급Masson염색관찰각조대서신장병리형태화효원섬유침적；ELISA법측정각조대서신조직AngⅡ함량；실시정량PCR검측대서신조직전화생장인자(TGF)β1、OPN mRNA적표체.결과 약물간예각조대서UAER、Ccr교DM조현저감소(균P＜ 0.05).DM조대서신소구비대,계막기질증생,신소구급소관간질유대량효원섬유침적；약물간예후,신소구급신소관상술병변감경.DM조대서신조직AngⅡ수평급TGF-β1、OPN mRNA표체균현저승고(균P＜0.05),급여정굴진급액패사탄간예후,AngⅡ、TGF-β1、OPN mRNA표체현저강저(균P＜0.05),차수착액패사탄제량적체증이체감.상관분석결과현시,DM조대서신조직AngⅡ수평여OPN mRNA적표체정정상관(r=0.74,P＜0.01).결론 액패사탄통과감소신장국부AngⅡ수평,진이감소신장TGF-β1、OPN mRNA적표체,최종감경소관간질섬유화,발휘신장보호작용,차저충보호작용구유제량의뢰성.
Objective To explore the effect of different doses of irbesartan on osteopontin expression and fibrosis in diabetic rat kidney. Methods Sixty-three g-week old male Wistar rat were randomly divided into control group (Ctrl group,n=7),diabetes group (DM group,n=14),30 mg·kg-1d-1 hydralazine administrated group (DM+Hyd group,n=12),25 mg·kg-1·d-1 irbesartan administrated group (DM+Irb25 group,n=10),50 mg·kg-1 ·d-1 irbesartan administrated group(DM+Irb50 group,n=9) and 200 mg·kg-1·d-1 irbesartan administrated group (DM+Irb200 group,n=11).Four weeks after modeling,rats were administered with the corresponding dose of irbesartan.After 12 weeks,urinary albumin excretion rate (UAER),endogenous creatinine clearance rate (Ccr) were measured; morphology and collagen deposition in rat kidney were observed by PAS and Masson staining respectively; Ang Ⅱ content in kidney was measured by ELISA; renal tissue TGF-β1 and OPN mRNA expression were detected by real-time PCR. Results UAER and Ccr in the intervention groups of irbesartan were significantly decreased compared with DM group (P＜0.05).UAER and Ccr in DM+Irb200 group were significantly lower than those in DM+Irb25 group and DM + Irb50 group (P＜0.05).Glomerular hypertrophy,mesangial matrix expansion,tubular lesions and deposition of collagen fiber were siginficant in diabetic rats compared with Ctrl,and prevented after administration with different doses of irbesartan.Ang Ⅱ protein level and TGF-β1,OPN mRNA expression in renal tissue of diabetic rats were significantly higher than those in Ctrl group.Ang Ⅱ,TGF-β1,and OPN mRNA expression was significantly reduced after administration with different doses of irbesartan,and with the increase of irbesartan,the above indicators were decreased P＜0.05).Renal local Ang Ⅱ level was positively correlated with OPN mRNA expression (r=0.74,P＜0.01). Conclusion Irbesartan reduces renal TGF-β1,OPN mRNA expression by decreasing kidney local Ang Ⅱ in dose-dependent manner,and eventually reduces tubulointerstitial fibrosis,which plays a role in kidney protection.
