浙江医学
浙江醫學
절강의학
ZHEJIANG MEDICAL JOURNAL
2014年
7期
545-549
,共5页
罗蕴龄%陈宜方%何东元%陈建国
囉蘊齡%陳宜方%何東元%陳建國
라온령%진의방%하동원%진건국
黄芪甲苷%糖尿病肾病%足细胞%α3β1整合素
黃芪甲苷%糖尿病腎病%足細胞%α3β1整閤素
황기갑감%당뇨병신병%족세포%α3β1정합소
Astragaloside IV%Diabetic nephropathy%Podocyte%α3β1 Integrin
目的：探讨黄芪甲苷（AS- IV）对糖尿病肾病（DN）大鼠足细胞的保护作用及其机制，为DN早期防治开辟一条新途径。方法体重180~200g健康雄性SD大鼠45只按配伍法分为正常对照组（NC组）、DN组和AS- IV治疗组（DN+AS- IV组），链脲佐菌素腹腔注射建立大鼠早期DN模型。DN+AS- IV组大鼠在造模前2周予AS- IV 10mg/（kg·d）灌胃预处理至实验结束，共14周。造模后第6、12周末收集并测定24h尿量及尿蛋白；同时各组按抽签法选取5只大鼠测体重，处死大鼠后测血生化指标，取肾组织，光镜观察肾脏病理病理变化，电镜观察足细胞形态变化，肾母细胞瘤抑制基因1（WT1）免疫组织化学染色观察肾小球足细胞密度变化，Western blot法测定大鼠肾皮质α3β1整合素蛋白水平的变化。结果与NC组相比，DN组大鼠血糖和24h尿蛋白增高，肾脏肾小球系膜区增生，足细胞足突融合，肾小球足细胞数量减少，α3β1整合素蛋白水平下降，差异有统计学意义（P＜0.05）。AS- IV可显著改善DN大鼠蛋白尿，抑制肾小球系膜区增生，抑制足细胞足突融合和数目减少，上调α3β1整合素表达。结论 AS- IV对早期DN大鼠足细胞具有保护作用，可能与其上调足细胞α3β1整合素表达相关。
目的：探討黃芪甲苷（AS- IV）對糖尿病腎病（DN）大鼠足細胞的保護作用及其機製，為DN早期防治開闢一條新途徑。方法體重180~200g健康雄性SD大鼠45隻按配伍法分為正常對照組（NC組）、DN組和AS- IV治療組（DN+AS- IV組），鏈脲佐菌素腹腔註射建立大鼠早期DN模型。DN+AS- IV組大鼠在造模前2週予AS- IV 10mg/（kg·d）灌胃預處理至實驗結束，共14週。造模後第6、12週末收集併測定24h尿量及尿蛋白；同時各組按抽籤法選取5隻大鼠測體重，處死大鼠後測血生化指標，取腎組織，光鏡觀察腎髒病理病理變化，電鏡觀察足細胞形態變化，腎母細胞瘤抑製基因1（WT1）免疫組織化學染色觀察腎小毬足細胞密度變化，Western blot法測定大鼠腎皮質α3β1整閤素蛋白水平的變化。結果與NC組相比，DN組大鼠血糖和24h尿蛋白增高，腎髒腎小毬繫膜區增生，足細胞足突融閤，腎小毬足細胞數量減少，α3β1整閤素蛋白水平下降，差異有統計學意義（P＜0.05）。AS- IV可顯著改善DN大鼠蛋白尿，抑製腎小毬繫膜區增生，抑製足細胞足突融閤和數目減少，上調α3β1整閤素錶達。結論 AS- IV對早期DN大鼠足細胞具有保護作用，可能與其上調足細胞α3β1整閤素錶達相關。
목적：탐토황기갑감（AS- IV）대당뇨병신병（DN）대서족세포적보호작용급기궤제，위DN조기방치개벽일조신도경。방법체중180~200g건강웅성SD대서45지안배오법분위정상대조조（NC조）、DN조화AS- IV치료조（DN+AS- IV조），련뇨좌균소복강주사건립대서조기DN모형。DN+AS- IV조대서재조모전2주여AS- IV 10mg/（kg·d）관위예처리지실험결속，공14주。조모후제6、12주말수집병측정24h뇨량급뇨단백；동시각조안추첨법선취5지대서측체중，처사대서후측혈생화지표，취신조직，광경관찰신장병리병리변화，전경관찰족세포형태변화，신모세포류억제기인1（WT1）면역조직화학염색관찰신소구족세포밀도변화，Western blot법측정대서신피질α3β1정합소단백수평적변화。결과여NC조상비，DN조대서혈당화24h뇨단백증고，신장신소구계막구증생，족세포족돌융합，신소구족세포수량감소，α3β1정합소단백수평하강，차이유통계학의의（P＜0.05）。AS- IV가현저개선DN대서단백뇨，억제신소구계막구증생，억제족세포족돌융합화수목감소，상조α3β1정합소표체。결론 AS- IV대조기DN대서족세포구유보호작용，가능여기상조족세포α3β1정합소표체상관。
Objective To investigate the protect effects of astragaloside IV(AS- IV) on diabetic nephropathy rat podocytes and explore its mechanism. Methods Healthy male Sprague- Dawley (SD) rats of 180~200g were randomly divided into normal control group(NC), diabetic nephropathy group(DN) and diabetic nephropathy with AS- IV treatment group(DN+AS- IV). DN was induced by intraperitoneal injection of streptozotocin. AS- IV treatment was started 2 weeks before STZ injection and lasted 14 weeks. 24 hour urine were col ected and 24 hour urinary protein were measured at the end of the 6th,12th week after STZ injec-tion. At the end of 6th and 12th week after STZ injection, rats were sacrificed and the blood samples were col ected for measuring biochemical parameters. The kidneys were harvested for histopathology, immunohistochemistry, electron microscopy and West-ern blot examinations, and the renal pathology, morphological changes of podocytes, podocyte density changes and expression ofα3β1 integrin protein were analyzed. Results In STZ- induced DN rats severe hyperglycemia and proteinuria were devel-oped. Mesangial expansion, increased podocyte loss and decreased integrin α3 and β1 expression were detected in DN rats. Treatment with AS- IV10mg/ (kg·d) for 14 weeks ameliorated proteinuria and podocyte foot process effacement, attenuated the loss of podocytes in glomerules and up- regulated the expression of integrinα3 andβ1 in podocytes. Conclusion AS- IV may protect podocyte and ameliorate diabetic nephropathy by restoring the expression ofα3β1 integrin in diabetic rats.
