GLP-1，Exendin-4和C肽对大鼠肾血流的影响

Effects of GLP-1, Exendin-4 and C-peptide on renal blood flow in rats

目的比较胰升糖素样肽1（GLP-1）、Exendin-4和c肽对血糖正常和高血糖大鼠肾血流（RBF）的影响。方法雄性成年Wistar大鼠随机分为GLP-1组、Exendin-4组、C肽组和对照组。每组再分为基础组和糖负荷组（每组6～7只大鼠）。采用微球技术测定大鼠RBF和肾上腺血流，同时测定平均动脉压和血糖。结果高血糖时RBF显著增加（P〈0．01）。GLP-1显著增加基础RBF[（7．540±0．909vs4．775±0．638）ml·min^-1·g^-1肾组织，P〈0．05]，进一步增加糖负荷后RBF[（11．054±1．236vs8．952±1．142）ml·min^-1·g^-1肾组织，P〉0．05]。Exendin-4不影响基础和糖负荷后RBF，但阻断了高血糖诱导的RBF增加。C肽显著增加大鼠基础RBF（P〈0．05），对糖负荷后RBF无影响。结论GLP-1、Exendin-4和C肽均具有调节RBF的作用。Exendin-4阻断高糖诱导的RBF增加，改善高血糖时的肾脏血流动力学异常。

Objective To evaluate the effects of glucagon-like peptide-1 （GLP-1）, Exendin-4 and C- peptide on renal blood flow（RBF） in normoglycaemic and hyperglycaemic rats. Methods Adult male Wistar rats were divided into 4 groups and intravenously given saline （or 30% glucose, as control）, GLP-1, Exendin4 and C- peptide respectively. Mean arterial blood pressure was monitored and microsphere technique was adopted to measure RBF and adrenal blood flow. Results Glucose administration augmented RBF significantly （ P〈0.01 ）. GLP-1 significantly increased basal RBF （ P〈0.05 ） , and further increased RBF after glucose administration （ P〉 0.05）. Exendin-4 had rio effect on either basal RBF or post-glucose-load RBF, but prevented the glucose-induced increase of RBF. C-peptide enhanced basal RBF （P〈0. 01 ）, but did not affect RBF after glucose injection. Conclusion GLP-1, Exendin-4 and C-peptide exert a regulatory effect on RBF in Wistar rats. Exendin-4 prevents the increment of RBF in hyperglycaemic rats and might be a promising agent against diabetic nephropathy.