血管生成素及其受体Tie2在大龄GK大鼠肾皮质中的表达及意义

目的：研究血管生成素（Angiopoietins）及其受体Tie2在大龄GK大鼠肾皮质中的表达及其意义。方法：自发性糖尿病动物（Goto—Kakizaki，GK）大鼠（GK组），在52周时取肾皮质进行病理切片，光镜检查；电镜观察超微结构改变；Re—alt—time RT—PCR和免疫组化法检测大鼠肾皮质血管生成素Ⅰ（Angiopoietin Ⅰ，Ang Ⅰ）、血管生成素Ⅱ（AngiopoietinⅡ，AngⅡ）、血管生成素受体Tie2和血管内皮生长因子（vascular endothelial growth factor，VEGF）mRNA和蛋白质的表达。并与链脲佐菌素（streptozocin，STZ）诱导的糖尿病大鼠（DM组）及正常SD大鼠（SD组）肾皮质进行比较。将Ang Ⅰ、AngⅡ、Tie2和VEGF与肾小球体积和肾小球细胞外基质（ECM）做相关性分析。结果：与SD组比较，GK组大鼠光镜下无病理改变；而DM组大鼠出现肾小球肥大和系膜基质增生；电镜下观察到GK组大鼠肾小球基底膜增厚。Real—time RT—PCR结果显示GK组肾皮质AngI、AngⅡ、Tie2、VEGFmRNA表达与SD对照组比较无统计学差异（P〉0．05）；而其AngⅡ和VEGF mRNA表达较DM组显著性减少（P〈0.05）。免疫组化半定量分析结果显示，GK组大鼠与SD组相比其肾皮质Ang Ⅰ表达显著性增高（P〈0．05），而AngⅡ、Tie2和VEGF的表达无统计学差异。AngⅡ、Tie2和VEGF与肾小球体积呈显著正相关，VEGF与肾小球ECM呈显著正相关。结论：大龄GK大鼠仅有轻微早期糖尿病肾脏改变，Ang Ⅰ表达增高可能是GK大鼠不易发生严重糖尿病肾损害的原因之一，AngⅡ和VEGF可能参与了糖尿病肾病的发病，其机制可能是通过促进血管增生和ECM增多。

Expressions of Angiopoietins and its Receptors Tie2 In the Renal Contex of Aged GK Rats

Objective：To investigate angiopoietins and its receptor Tie2 in the renal cortex of GK rat, a spontaneous type 2 diabetes animal model. Methods： The Goto - Kakizaki （GK） rats（GK group）, a model of non insulin- dependent diabetes mellitns,were sacrificed at the 52nd week. Light microscopy and Electron microscopy were carried out on renal tissue. Serum samples were obtained for the measurement of serum creatinine. Expressions of angiopoietins, VEGF and Tie2 were measured by real - time RT-PCR and I mmunohistochemistry. Hyperglyeaemia was induced in four weeks old SD rats by streptozoein and age - matched SD rats without any intervention were set as control. Results： No features of diabetic nephropathy were detected by light microscopy in GK rats while slightly increased glomerular volumes were seen in STZ rats. Thickening of the GBM was apparent in GK rats by electron microscopy. Real - time RT - PCR showed no change of angiopoietins and VEGF mRNA in GK rats while STZ rats showed increased Ang Ⅱ and VEGF mRNA level in kidney （ P 〈 0.05 ） which play an important role in the initiation of neovascularization. Quantitation of immunostaining showed angl were higher in Gk rats while Ang Ⅱ ,Tie2 and VEGF were increased in STZ rats（ P〈0.05）. Ang Ⅱ ,Tie2 and VEGF were positively correlated with glomerular volume. VEGF were positively correlated with glomerular extracellular matrix value. Conclusion： The increased AngI in GK rats contribute to which do not develop into overt diabeticnephropathy. Increased ang Ⅱ and VEGF may develop into diabetic nephropathy through angiogenesis and increasing glomerular volume.