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作 者:高杨[1] 吴芹[1] 杨丹莉[1] 邓江[1] 黄燮南[1]
机构地区:[1]贵州省基础药理重点实验室暨遵义医学院药理学教研室,贵州遵义563000
出 处:《中国药理学通报》2012年第3期388-392,共5页Chinese Pharmacological Bulletin
基 金:贵州省优秀科技教育人才省长专项基金项目[No黔省合字(2007)53号];贵州省科技厅联合基金[黔科合J字LKZ(2010)31号]
摘 要:目的探讨人参皂苷Rg1(Ginsenoside Rg1,Rg1)抗球囊损伤所致血管内膜异常增生的作用机制。方法利用♂SD(Spragye-Dawley)大鼠建立颈总动脉球囊损伤引起内膜异常增生模型,制模后次日起,每日腹腔注射Rg1 4、8、16mg.kg-1,模型组与假手术组给予等体积生理盐水,连续给药14天后取损伤侧颈动脉,石蜡切片后行H.E.染色,光镜下观察颈动脉内膜组织形态学变化,并用Q Win图像处理与分析系统计算新生内膜面积及内膜/中膜面积的比值;比色法检测大鼠血浆中超氧化物歧化酶(SOD)的活力和丙二醛(MDA)的含量;另用实时荧光定量PCR(Real-Time RT-PCR)法检测内皮型一氧化氮合酶(eNOS)mRNA的表达。结果光镜发现,Rg1给药可明显改善球囊损伤所致血管内膜组织形态学的异常;与模型组比较,Rg1能呈剂量依赖性地减小新生内膜面积和内膜面积/中膜面积的比值(P<0.01)。球囊损伤使大鼠血浆SOD活力降低,MDA含量增加,损伤血管壁的eNOS mRNA表达明显下调,而Rg1则使血浆SOD活力明显升高(P<0.05)、MDA含量明显下降(P<0.01)。小剂量Rg1使eNOS mRNA的表达趋于升高,中、高剂量Rg1则明显上调eNOS mRNA的表达(P<0.01)。结论 Rg1抗球囊损伤所致大鼠颈动脉内膜增生作用可能与其抗氧化和促进eNOS表达,从而增加NO生成有关。Aim To investigate the mechanisms of the inhibitory effect of ginsenoside Rg1(Rg1) on vascular neointimal hyperplasia induced by balloon-injury in rats.Methods The balloon-injured rat carotid artery model was established by rubbing the endothelia with a balloon in male Sprague-Dawley rats.Animals were then injected with distilled water(model group and sham operation group) or Rg1 4 mg·kg-1,8 mg·kg-1 and 16 mg·kg-1 for 14 consecutive days,then the injuried artery was taken for HE staining.The vascular intimal hyperplasia level was evidenced by histopathological observation and the neointimal area as well as the ratio of neointimal area/media area was detected.For probing the mechanisms,the plasma superoxide dismutase(SOD) activities and maleic dialdehyde(MDA) levels were detected,and the expression of endothelial nitric oxide synthase(eNOS) mRNA levels were analyzed by Real-Time PCR.Results Compared with the endothelia rubbing model group,Rg1 medication significantly improved the histopathological changes induced by balloon-injury,decreased the elevated neointimal area and the ratio of neointimal area/ media area;Rg1 administration could also increase the lowered plasma SOD activities,and decrease the elevated MDA levels.When the doses were at 8 mg·kg-1 and 16 mg·kg-1,Rg1 could significantly up-regulate the eNOS mRNA expression which was inhibited by balloon-injury.Conclusion The mechanisms by which Rg1 inhibits the vascular neointimal hyperplasia induced by ballon-injury in rats may be related to its anti-oxidant actions and up-regulating eNOS expression.
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