摘要
目的明确氯吡格雷对实验性大鼠胃溃疡愈合的影响,并从微血管形成的角度探讨其延缓胃溃疡愈合的机制。方法以乙酸性大鼠胃溃疡模型为基础,将22只大鼠分为模型组(n=6)、氯吡格雷组(n=8)和生理盐水组(n=8),观察氯吡格雷对胃溃疡愈合的影响,及对溃疡底部微血管密度(microvessel density,MVD)、胃黏膜内皮抑素(endostatin,ES)及血管内皮生长因子A165(vascular endothelial growth factor A165,VEGF-A165)表达的影响。结果制模术后第10天,氯吡格雷组和生理盐水组溃疡面积分别为(11±3.07)mm2、(7±1.85)mm2,差异有统计学意义(P=0.023 0)。氯吡格雷组溃疡底部MVD显著低于生理盐水组(P=0.011 4)。氯吡格雷组胃黏膜VEGF-A165含量显著低于生理盐水组(P<0.01),ES含量显著高于生理盐水组(P<0.01)。溃疡底部MVD与胃黏膜VEGF-A165含量正相关(r=0.688 8、P=0.003 2),与胃黏膜ES含量负相关(r=-0.767 1、P=0.000 5)。结论氯吡格雷可显著延缓乙酸性大鼠胃溃疡愈合,推测可能是通过调节胃黏膜VEGF-A165及ES的表达以抑制溃疡底部的微血管形成,从而使损伤黏膜修复受阻。
Objective To identify the effect of clopidogrel on the gastric ulcer healing in experimental rats and to explore the underlying mechanisms from the aspect of angiogenesis. Methods Acetic acid was introduced into the serosal surface of the gastic bodies to induce ulcers in 22 rats, then they were divided into model （ n = 6） ,clopidogrel （ n = 8） and normal saline （ n = 8） group. The effects of ctopidogrel on the healing of gastric ulcer, on microvessel density （MVD） at the bottom of ulcers, on the protein expression of endostatin （ES） and vascular endothelial growth factor-A165 （VEGF-A165） in gastric mucosa were observed. Results Ten days after ulcer inducton, the ulcer area in clopidogrel group and NS group were （I 1 -＋ 3.07） mm2 and （7-＋ 1.85） mm2 respectively, with significant difference （P = 0. 023 0）. The MVD in clopidogrel group was significantly lower than that in NS group （P = 0. 011. 4）. The VEGF-A165 concentration of gastric mucosa in clopidogrel group was significantly lower than that in NS group （ P 〈0.0l ）. The ES concentration of gastric mucosa in clopidogrel group was significantly higher than that in NS group （P 〈 0.01 ）. The MVD at the bottom of ulcers was positively correlated with the concentration of VEGF-A165 （ r = 0. 688 8, P = 0.1103 2）, while negatively correlated with the concentration of ES （r = - 0. 767 1,P= 0.0005）. Conclusions Clopidogrel can signifficantly delay the experimental rats, where inhibiting of angiogenesis at the bottom of ulcers of VEGF-A165 and ES in gastric mucosa might involve in the mechanism. healing of gastric ulcer in by regulating the expression
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2013年第1期50-54,共5页
Fudan University Journal of Medical Sciences
