氯化钴干预条件下糖尿病大鼠肾组织HIF-1α的表达及意义

Hypoxia-inducible Factor-1α Expression and Its Significance on Nephridial Tissue of Diabetic Rats in Cobalt Chloride Intervention

目的研究氯化钴(CoCl2)干预条件下糖尿病(diabetes mellitus,DM)大鼠肾组织缺氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α)的表达及意义。方法按数字随机化原则取8只为正常对照组(CTL组),16只为模型组,建立糖尿病肾病大鼠模型,并随机均分为糖尿病组(DM组)和CoCl2治疗组(CoCl2组)。检测相关生化指标,免疫组化学检测实验大鼠HIF-1α表达和分布,蛋白免疫印迹法(Western Blotting)检测肾脏组织HIF-1α蛋白表达。结果CTL组肾脏组织无HIF-1α表达,DM组HIF-1α主要分布于肾小管上皮细胞的胞浆和胞核;CoCl2组HIF-1α平均光密度显著高于DM组(P<0.05),其HIF-1α蛋白表达水平较DM组显著增加(P<0.05)。结论缺氧参与糖尿病肾脏疾病(diabetic kidney disease,DKD)早期肾小管间质损伤,化学性低氧模拟剂CoCl2可通过上调HIF-α减轻蛋白尿和肾小管间质损伤,延缓DKD进展。

Objective To investigate Hypoxia-inducible factor-1αexpression and its significance on nephridial tissue of diabetic rats in cobalt chloride intervention.Methods Selected 8 rats as normal control group（CTL group）and 16 rats as model group randomly,then divided the model group into diabetic model group（DM group）and treatment group（CoCl2 group）.Detected the correlative biochemistry index,the expression and distribution of HIF-1αof rats was evaluated by immunohistochemistry analysis,and the expression of HIF-1αof nephridial tissue was detected by western blotting.Results The nephridial tissue in CTL group had no HIF-1αexpression.HIF-1αexpression in DM group mainly distributed throughout the endochylema and karyon of renal tubular epithelial cell.The average optical of HIF-1αin CoCl2 group was significantly higher than that of DM group（P〈0.05）,and the expression level of HIF-1αin CoCl2 group remarkably increased compared with DM group（P〈0.05）.Conclusion Hypoxia can play role in treatment of early renal tubular lesions in diabetic kidney disease（DKD）.Cobalt chloride intervention can mitigate albuminuria and kidney tubules injury and postponing the progression of DKD by elevating HIF-1αexpression.