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iNOS抑制剂对大鼠腹主动脉瘤平滑肌凋亡的抑制作用

Inhibitory effect of iNOS inhibitor on the apoptosis of rat abdominal aortic aneurysm smooth muscle cells

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【作者】 林华鹏乔森

【Author】 LIN Hua-peng;QIAO Sen;Department of Hepatobiliary Surgery, Jining NO.1 Pepole’s Hospital;

【机构】 济宁市第一人民医院肝胆外科

【摘要】 目的:建立腹主动脉瘤动物模型,阐述iNOS抑制剂对大鼠腹主动脉瘤平滑肌凋亡的作用,为临床治疗小腹主动脉瘤寻找新的理论依据。方法:通过弹力蛋白酶(25 U/mL)灌注大鼠腹主动脉建立SD大鼠腹主动脉瘤动物模型,阴性对照组予以生理盐水灌注腹主动脉(27只),术后阴性对照组(27只)和阳性对照(27)组均予以腹腔内注射生理盐水,实验组术后腹腔内注射iNOS抑制剂药物盐酸氨基胍(200 mg/kg),术后第2、7、14天分别取大鼠动脉血检测血清中NO的含量,腹主动脉瘤标本行iNOS免疫组化、TUNEL染色检测动脉瘤平滑肌细胞的凋亡情况。结果:应用弹力蛋白酶灌注大鼠腹主动脉建立腹主动脉瘤灌注模型成功率高,阳性对照组成瘤率分别为10%、60%、80%,治疗组分别为:0、10%、20%,阴性对照组无动脉瘤形成,治疗组和阴性对照组低于阳性对照组(P<0.05),阳性对照组中NO含量从第2天开始逐渐升高,7 d达到高峰并维持在较高水平,治疗组血清中的NO含量比其他两组低(P<0.05);iNOS在阳性对照组中强表达,在其它两组轻度表达;TUNEL结果显示,阳性对照组中可见大量凋亡细胞,自7 d后呈明显增大趋势,至观察结束(2周)逐渐增高,阳性对照组比阴性治疗组和阴性对照组要高(P<0.05)。结论:iNOS抑制显著降低血清中NO含量,减轻中膜平滑肌细胞的凋亡,从而抑制了腹主动脉瘤的形成。为临床应用iNOS抑制剂治疗和控制AAA的发展提供了理论依据。

【Abstract】 Objective: To explore the establishment of an animal model of abdominal aortic aneurysm(AAA), and elaborate the role of iNOS inhibitor in the smooth muscle apoptosis of abdominal aortic aneurysm in rats, to find a new theoretical basis for the clinical treatment of small drugsAAA. Methods: SD rats underwent intra-aortic elastase(25U/mL)perfusion to induce AAAs, the positive control group(30)and experiment group(30)use elastase perfusion while the negative control group(30)gives the saline perfusion.After operation the positive and negative control groups were treated with intraperitoneal injections of saline,experimental group injects the iNOS inhibitor Aminoguanidi hydrochloride; Postoperative second, 7, and 14 days, The NO content in the serum and specimen of abdominal aortic aneurysm was detected by iNOS Immuno histochemistry and Terminal Transferase-mediated dUTP Nick End-Labeling(TUNEL)to evaluate distribution of smooth muscle apoptosis in abdominal aortic aneurysm. Results: Underwent intra-aortic elastase perfusion to induce AAAs have a high-success-rate. Rate of AAA formation in positive control group 10%, 60%,80%, respectively. The treatment group was 0%, 10%, 20%, and the negative control group was not formed. The treatment group and the negative control group were lower than the positive control group, there were significant differences. In the positive control group, NO content increased gradually from second days, 7 days to reach the peak and maintained at a higher level, the treatment group serum NO content was lower than the other two groups, there was significant difference(P <0.05),iNOS was strong expression in the positive control group, in the other two groups of mild expression.TUNEL results showed that a lot of apoptotic cells in the positive control group, after 7 days showed a significant increase trend, to observe the end(2 weeks)gradually increased.,The positive control group was higher than the negative control group and the negative control group, there was significant difference(P <0.05). Conclusion: iNOS inhibitors significantly decreased the content of NO in serum, reduced the apoptosis of smooth muscle cells, and inhibited the formation of abdominal aortic aneurysm. To provide theoretical basis for clinical application of iNOS inhibitors in the treatment and control of AAA.

  • 【文献出处】 中国现代普通外科进展 ,Chinese Journal of Current Advances in General Surgery , 编辑部邮箱 ,2017年03期
  • 【分类号】R543.1
  • 【被引频次】1
  • 【下载频次】107
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