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前列腺素E1干预大鼠血管球囊损伤后再狭窄的机制探讨

PGE1 affects against the occurrence of vascular restenosis after balloon injury and its mechanisms

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【作者】 冯国清赵胜程红梅付润芳刘红杨万雷秦攀

【Author】 FENG Guo-qing,ZHAO Sheng, CHENG Hong-mei,FU Run-fang,LIU Hong, YANG Wan-lei, QIN Pan (Dept of Pharmacology, Medical college of Zhengzhou University, Zhengzhou 450052,China)

【机构】 郑州大学医学院药理学教研室杭州市萧山区妇幼保健院儿科郑州市食品药品监督管理局郑州大学医学院药理学教研室 河南郑州450052浙江杭州30006河南郑州450006河南郑州450052河南郑州450052

【摘要】 目的观察前列腺素E1(PGE1)在大鼠血管球囊损伤术后对血小板颗粒膜蛋白(GMP140)、D二聚体(Ddimer)、血浆内皮素(ET)及炎性细胞因子白介素1β(IL1β)、白介素6(IL6)、肿瘤坏死因子(TNFα)水平的影响,探讨PGE1对血管球囊损伤术后再狭窄形成的防治机制。方法采用大鼠腹主动脉球囊损伤模型,用药组术前连续5d经尾静脉给予PGE1(8、24、72μg·kg-1),模型组及假手术组给予等容积NS。各组动物于术后6h、24h、10d、21d4个时间点取血,采用酶连免疫吸附试验双抗体夹心法测定血浆中GMP140、Ddimer的含量;采用平衡法测定血浆中内皮素及血清中IL1β、IL6、TNFα的含量。结果与假手术组比球囊损伤模型组术后6h血浆GMP140、Ddimer含量明显升高(P<0.01),PGE1(8、24、72μg·kg-1)各组血浆GMPI40和D二聚体的含量显著降低(P<0.01)。模型组血浆ET含量6h开始增加,24h达高峰,10d降至正常。PGE1(24、72μg·kg-1)两组能明显降低6、24h血浆ET含量(P<0.01)。血管球囊损伤术后6h,模型组TNFα含量达高峰,而IL1β、IL6则在术后24h达高峰,PGE1各组均可在高峰时显著降低IL1β、IL6、TNFα的含量,与模型组相比差异显著(P<0.01),并呈良好的剂量相关性(r=0.747,0.907,0.747)。结论PGE1在大鼠血管球囊损伤术后可降低GMP140、Ddimer及血浆中ET、血清中IL1β、IL6、TNF浕水平的作用,是其干预血管再狭窄形成的重要机制。

【Abstract】 Aim The change of injured aortic endothelium, GMP-140, and D-dimer and the plasma concentration of ET and the serum concentration of IL-1β, IL-6, and TNF-αat different time points were studied to evaluate the effects of PGE1 preventing RS after balloon injury and its mechanisms. Methods Used a balloon injury to make the rat model of abdominal aorta endothelium injury. Three PGE1 dost (8、24、72 μg·kg -1) was injected via tail vein 5 days before operation, equal volume of normal saline was injected in model and sham operation groups. The underlying experiments were performed in each group at the 6th, 24th and poth, 21st day after opcration: Collected the blood sample after operation, then the plasma was assayed of GMP-140, D-dimer and ET concentration of the plasma and IL-1β,IL-6,TNF-α concentration of the serum was measured by balanced method. Results The plasma levels of GMP-140 and D-dimer in model group were significantly higher than that in sham group (P<0.01). PGE1 (8、24、72 μg·kg -1) could significantly decrease the plasma levels of GMP-140 and D-dimer (P<0.01). The plasma level of ET increased at 6th hour after PTCA, reached maximum in 24th hours, then reduced normal level. PGE1 (24、72 μg·kg -1) could significantly decrease the plasma levels of ET in 6th hour 24th hour groups (P<0.01). The serum level of TNF-α quickly renched maximum in 6th hours, the scrum levels of IL-1β, IL-6 reuthed maximum in 24th hours. PGE1 (8、24、72 μg·kg -1) could significantly decrease the maximum serum levels of IL-1β, IL-6, TNF-α. Conclusions The reduction of GMP-140,D-dimer and the plasma levels of ET and the serum levels of IL-1β, IL-6 and TNF-α plays an important role in the protective mechanisms against vascular RS of PGE1.

  • 【文献出处】 中国药理学通报 ,Chinese Pharmacological Bulletin , 编辑部邮箱 ,2005年07期
  • 【分类号】R965
  • 【被引频次】4
  • 【下载频次】83
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