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钠氢交换抑制剂对兔髂动脉球囊损伤后血管狭窄干预作用研究

Study of the Effectiveness of Amiloride on Angiostenosis after Balloon Injuries in Rabbits
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摘要 目的:建立兔髂动脉球囊损伤模型,观察钠氢交换(NHE)抑制剂(Amiloride)对血管狭窄的干预作用。方法:32只新西兰白兔随机分为干预组(12只)、对照组(10只)及假术组(10只);建立兔髂动脉球囊损伤模型。干预组于术前3d予Amiloride[5mg(kg·d)]、对照组以相同剂量NS腹腔注射,至术后28d取材;取髂动脉行苏木精伊红染色、αactin免疫组化染色、Masson三色染色,观察血管管腔、中膜与内膜面积变化、平滑肌细胞增殖、细胞外基质(ECM)变化情况。结果:兔髂动脉球囊损伤后4周出现明显管腔狭窄,新生内膜生长,平滑肌层增生;干预组、对照组、假术组髂动脉管腔面积各为(0.91±0.23)mm2、(0.68±0.19)mm2、(1.08±0.17)mm2,F=7.631,P<0.01;新生内膜面积各为(0.27±0.15)mm2、(0.67±0.24)mm2、(0.05±0.03)mm2,F=36.974,P<0.01;内膜中膜面积比各为1.21±0.24、1.39±0.26、0.15±0.08,F=7.562,P<0.01;经Amiloride干预后管腔面积明显增大,内膜面积显著下降,内膜中膜面积比下降。干预组与对照组内膜比较,αactin染色阳性面积减小[(4164.15±1788.37)μm2vs.(16328.31±6220.27)μm2,P<0.01];Masson染色绿色面积下降[(8910.62±7041.62)μm2vs(333558.76±7290.17)μm2,P<0.01],提示干预组内膜平滑肌增生及ECM增生均减轻。结论:Amiloride可抑制球囊损伤兔髂动脉所致血管管腔缩小、内膜增生、分泌ECM,减轻血管狭窄,提示其可能在预防经皮冠状动脉内成形术术后血管再狭窄起一定作用。 Objective:To explore the effectiveness of the sodium-hydrogen exchanger(NHE)inhibitor(Amiloride)on angiostenosis after balloon injuries in rabbits.Methods:Thirty-two New Zealand white rabbits were randomly divided into intervention group(IG)with 12 rabbits,control group(CG)with 10 rabbits and pseudo-operation group(PG)with 10 rabbits.Amiloride[5?mg/(kg·d)]was injected intraperitoneally,3 times a day in IG and the same dosage NS was used in the same way in CG till 28 days after operation.Then the rabbits were killed and the iliac arteries were taken out and stained with Hematoxylin-eosin,α-actin and Masson's trichrom to observe the morphologic changes of the vessel cave,neointima and the media layer and the vascular smooth muscle cell migration into the neointima and the extracellular matrix(ECM)in the vessel walls.Results:Four weeks after balloon injuries in rabbits,the cave of the iliac artery was extremely narrow and neointima was formed and the media layer was proliferated.Compared among IG,CG and PG,the cave areas were(0.91±0.23)mm^2,(0.68±0.19)mm^2,(1.08±0.17)mm^2(F=7.631,P<0.01)respectively.The intima areas of three groups were(0.27±02?5)mm^2,(0.67±0.24)mm^2,(0.05±0.03)mm^2(F=36.947,P<0.01)respectively.The ratios of intima to media area were(1.21±0.24),(1.39±0.26),(0.15±0.08)(F=7.562,P<0.01)respectively.After intervented by Amiloride,the vessel cave areas were enlarged and intima areas and the ratios of intima to media area were decreased.In IG compared with CG,the α-actin positive areas in neointima were decreased[(4?164.15±1?788.37μm^2 vs.(16?328.31±6?220.27)μm^2 with P<0.01]and the ECM areas in neointima were smaller[(8?910.62±7?041.62)μm^2 vs.(333?558.76±7?290.17)μm^2 with P<0.01].Conclusion:Amiloride can relieve the angiostenosis through increasing cave areas and decreasing neointima area and development of ECM.Maybe this kind of drug is useful in prevention of the (res-)tenosis after percutaneous transcoronary angioplasty.
出处 《汕头大学医学院学报》 2005年第2期88-90,93,F002,共5页 Journal of Shantou University Medical College
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