摘要
目的探讨缺氧诱导因子(HIF)-1α、血小板源性生长因子(PDGF)-A及PDGF-B在慢性肾功能衰竭大鼠肾组织中的表达及作用,观察六味地黄汤对其表达的影响。方法用5/6肾切除法复制慢性肾功能衰竭模型,分假手术组,模型组和六味地黄汤组。造模后12周,检测各组肾功能指标,HE染色法观察肾组织病理变化,Masson染色法观察肾组织胶原的沉积,免疫组化法和RT-PCR法分别检测HIF-1α、PDGF-A和PDGF-B在肾组织中的表达。结果 24 h尿蛋白、血尿素氮和血肌酐在模型组明显升高(P<0.01),六味地黄汤组则明显降低(P<0.01)。模型组肾间质纤维化明显,大量胶原纤维沉积;六味地黄汤组肾间质纤维化程度明显减轻,少量胶原纤维沉积。与假手术组比较,模型组肾组织中HIF-1α、PDGF-A及PDGF-B蛋白水平和基因表达均明显升高(P<0.01);与模型组比较,六味地黄汤组肾组织中HIF-1α、PDGF-A及PDGF-B蛋白水平和基因表达均明显降低(P<0.01),且PDGF-A和PDGF-B的表达与HIF-1α均呈正相关(P<0.01)。结论 HIF-1α可能通过上调PDGF-A和PDGF-B的表达促进肾间质纤维化,六味地黄汤可下调HIF-1α的表达,从而抑制肾间质纤维化。
Objective To explore the expression of HIF-1α,PDGF-A and PDGF-B in chronic renal failure rats,and observe the effect of Liuwei Dihuang Decoction on its expression.Methods Chronic renal failure model was made by 5/6 nephrectomy.Rats were divided into sham operation group,model group and Liuwei Dihuang Decoction group.Twelve weeks after modeling,the indexes of renal function were detected,HE staining was used to observe the renal pathological changes,Masson staining was used to observe the renal tissue collagen deposition,immunohistochemical method and RT-PCR method were used to detect the expression of HIF-1α,PDGF-A and PDGF-B in kidney tissue.Results The 24 h urine protein,blood urea nitrogen and creatinine were higher in model group and lower in Liuwei Dihuang Decoction group（P 0.01）.HE and Masson staining showed renal interstitial fibrosis significantly and large amounts of collagen fibers deposition in model group,while renal interstitial fibrosis was reduced significantly and a small amount of collagen fibers deposition in Liuwei Dihuang Decoction group.Compared with the sham operation group,HIF-1α,PDGF-A and PDGF-B protein level and gene expression were significantly increased in model group（P 0.01）.Compared with the model group,HIF-1α,PDGF-A and PDGF-B protein level and gene expression decreased significantly in Liuwei Dihuang Decoction group（P 0.01）.The expression of PDGF-A and PDGF-B were positively correlated with HIF-1α（P 0.01）.Conclusion HIF-1α may promote renal interstitial fibrosis through the up-regulation of PDGF-A and PDGF-B expression,Liuwei Dihuang Decoction can down-regulate the expression of HIF-1α,thereby inhibit renal interstitial fibrosis.
出处
《中国中医药信息杂志》
CAS
CSCD
2013年第4期44-47,共4页
Chinese Journal of Information on Traditional Chinese Medicine
基金
湖南省自然科学基金(09JJ3064)
湖南省高校创新平台开放基金(09K059)
关键词
慢性肾脏病
缺氧诱导因子1Α
大鼠
5
6肾切除
六味地黄汤
chronic kidney disease
hypoxia-inducible factor 1α
rats
5/6 nephrectomy
Liuwei Dihuang Decoction
