扎普司特对急性脑缺血大鼠局部脑血流量的影响

Effect of zaprinast on regional cerebral flow during acute cerebral ischemia in rats

目的探讨磷酸二酯酶5抑制剂扎普司特对急性脑缺血大鼠脑血流量的影响。方法选择雄性Wistar大鼠28只,随机分为磷酸盐缓冲剂(PBS)组和扎普司特组,每组14只。参照改良的Koizumi等线栓法,制作大鼠大脑中动脉局部缺血模型。经静脉分别注入PBS及扎普司特(10mg/kg)1ml,用激光多普勒流量仪连续测定缺血侧及对侧皮质局部脑血流量的变化;用免疫荧光法测定皮质环磷酸鸟苷(cGMP)的含量;用2,3,5-三苯基氯化四氮唑染色后测定脑梗死体积。结果扎普司特组缺血侧皮质的局部脑血流量较PBS组升高了30%±11%,而对侧没有升高;cGMP为(160±46)fmol/mg蛋白,与对侧皮质的(131±30)fmol/mg蛋白及PBS组的(106±29)fmol/mg蛋白相比,差异均有显著性(P<0·05)。扎普司特组和PBS组大鼠的皮质梗死体积分别为(135±16)、(202±64)mm3,差异有显著性(P<0·05)。结论扎普司特通过提高脑缺血侧大脑皮质的cGMP而提高了局部脑血流量。

Objective To investigate the effect of zaprinast （a phosphodiesterase-5 inhibitor） on cerebral blood flow during the acute cerebral ischemia in rats. Methods Twenty-eight male Wistar rats were selected and randomly assigned into phosphate buffer saline （PBS） and zaprinast groups （ n = 14 each group）. A model of focal ischemia following middle cerebral artery occlusion in rats was established according to Koizumi＇s suture method. PBS and zaprinast were intravenously infused with （10 mg/kg） 1 mL respectively the two groups. The changes of regional cerebral blood flow （rCBF） were continuously measured by laser-Doppler flowmetry in ischemic and contralateral sides; the cyclic guanosine mono-phosphate （cGMP） concentrations were determined by immumofluorescence method, and the volume of cerebral infarction was detected by using 2, 3, 5-triphenyltetrazolium chloride staining. Results The rCBF in the cortexes of ischemic sides in the zaprinast group increased 30 ± 11% as compared with the PBS group, while the rCBF did not increase in the contralateral sides; The cGMP was 160±46 fmol/mg protein, as compared with 131 ±30 fmol/mg in the eortexes of contralateral sides, and 106 ± 29 in the PBS group, there was significant difference （ P 〈 0. 05 ）. The volume of cerebral infarction in the zaprinast and PBS groups were 135 ±16 and 202 ±64 mm^3 respectively, and there was significant difference （P 〈0. 05）. Conclusion Zaprinast can selectively increase rCBF by elevating the cGMP levels in the ischemic penumbra of the cerebral cortex.