人和猪源性红细胞降压因子作用的比较

Comparasion of the Actions of Human and Porcine Erythrocyte-derived Depressing Factor

目的比较人和猪两种不同来源的内源性降压因子(erythrocyte-deriveddepressingfactor,EDDF)的降压作用及其作用机制。方法选用自发性高血压大鼠(SHR,n=5)和两肾一夹肾性高血压大鼠(2K-1C,n=7),分别观察猪和人源性EDDF的急性和慢性降压作用。用尾动脉脉压法比较EDDF对2K-1C和SHR大鼠的口服降压作用;用离体大鼠动脉环灌流法观察EDDF对两种高血压模型大鼠胸主动脉的舒张作用;用MTT法和流式细胞仪分别测定两种EDDF对2K-1C高血压大鼠胸主动脉血管平滑肌细胞(VSMCs)增殖及细胞周期的影响。结果两种来源的EDDF:(1)静脉给药均可显著降低大鼠的血压(P<0.05),口服后亦有明显降压效果;(2)对血管均有明显的呈内皮依赖性的舒张作用(P均<0.05);(3)均可明显抑制2K-1C大鼠VSMCs的增殖(P分别<0.01与0.05);并明显增加2K-1C大鼠VSMCsG1期的细胞数目(P<0.01),显著减少S期细胞数(P<0.01)。结论人和猪源性EDDF的降压效果、舒血管作用和抑制VSMCs增殖与调节细胞周期等方面的作用均无明显差异。

Objective To compare the action mechanisms of human and porcine derived erythrocyte-derived depressing factor(h-EDDF and p-EDDF)as well as the effects on blood pressure.Methods The experiments were carried out in spontaneously hypertensive rats(SHR,n=5)and two kidney-one click renal hypertensive rats(2K-1C,n=7).The acute and chronic effects of h-EDDF and p-EDDF on blood pressure were observed,blood pressure test using tail plethysmography under unanaesthetic state.Both EDDF were administrated via jugular vein and/or oral respectively.The isolated thoracic aorta ring perfusion assay was used to examine the effect of EDDF on the asodilation.Primary cultured VSMCs were prepared from the thoracic aorta media of2K-1C and normal Wistar rats.The effect of EDDF on proliferation of VSMCs were determined by MTT assay.The cell cycle of VSMCs was evaluated by flow cytometric.Results Both h-EDDF and p-EDDF could significantly decrease blood pressure of Wistar rats through intravenous administration and/or orally(P<0.01and P<0.05respectively).The contractile response of aorta in2K-1C rats to PE was significantly enhanced compared with that of the control(P<0.01)and both EDDF(10 -3 g/ml)remarkably induced a vasodilation with endothelium-dependent manner in SHR and2K-1C rats(P<0.05).h-EDDF and p-EDDF could significantly inhibit the proliferation of VSMCs from2K-1C and control rats.After24hours of exposure to EDDFs the cell number of G 0 /G 1 phase obviously increased and cell number in S phase was decreased(P<0.01,respectively).Conclusions It seems that the effects of h-EDDF and p-EDDF on blood pressure and vasodilation as well as inhibition of VSMCs proliferation and regulation of cell cycle have no significant difference.