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内皮素受体拮抗剂ETP-508对大鼠肺纤维化中P物质和MMP-2的影响

Effect of endothelin receptor antagonist-508 on substance P and matrixmetallop roteinase-2 in lung fibrosis of rats
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摘要 目的研究内皮素受体拮抗剂ETP-508对实验性大鼠肺纤维化组织中P物质(SP)和基质金属蛋白酶-2(MMP-2)变化的影响。方法实验分为博莱霉素组、ETP-508组和正常对照组。博莱霉素组和ETP-508组经气管内注射博莱霉素(5mg/kg)复制肺纤维化模型;正常对照组气管内注射等量0.9%氯化钠注射液。气管内注药次日后,ETP-508组腹腔注射ETP-508100μg/kg,隔日1次,博莱霉素组和正常对照组以等量0.9%氯化钠注射液替代。第7、28天分别处死动物,测定肺组织羟脯氨酸、SP和MMP-2含量,并进行病理组织学观察。结果博莱霉素组肺组织中羟脯氨酸含量明显高于正常对照组,病理为肺纤维化改变,第7、28天的SP水平均高于正常对照组和ETP-508组(P<0.01);第28天MMP-2水平较第7天水平降低(P<0.01),同时也低于正常对照组和ETP-508组(P<0.01)。ETP-508组第7、28天的SP和MMP-2水平与正常对照组相应时间点比较无明显差异(P>0.05)。结论 ETP-508具有抗肺纤维化形成作用,其机制可能与降低SP水平和阻止MMP-2水平下降的降解有关。 Objective To study the effect of endothelin receptor antagonist(ETP-508) on substance P(SP) and matrixmetallop roteinase-2(MMP-2) in lung fibrosis tissue of experimental rats. Methods Rats were divided into bleomycin(BLM) group, ETP-508 group and control group. A lung fibrosis model was induced by endotracheal injection of BLM(5mg/kg) for BLM and ETP-508 groups. Rats in control group received an equivalent endotracheal injection of 0.9% sodium chloride. On the next day, rats in ETP-508 group were treated with intraperitoneal injection of ETP-508(100 μ g/kg, every other day) while those in control and BLM groups received an equivalent endotracheal injection of 0.9% sodium chloride. Rats were killed on day 7 and 28, respectively. SP, MMP-2 and hydroxyproline(HYP) levels in their lung tissue were measured and histopathological change was observed. Results The HYP level was significantly higher in lung tissue of BLM group than in that of control group(P〈0.01). Lung fibrosis occurred in BLM group. The mean SP level was higher in lung tissue of BLM group than in that of control and ETP-508 groups on day 7 and 28(P〈0.01). The MMP-2 level was lower in BLM group on day 28 than on day 7 and than in control and ETP-508 groups(P〈0.01). No significant difference was found in SP and MMP-2 levels between control and ETP- 508 groups on day 7 and 28(P〉0.05). Conclusion ETP-508 can inhibit the formation of lung fibrosis by reducing the level of SP and suppressing the degradation of MMP-2.
出处 《军医进修学院学报》 CAS 2012年第1期75-77,共3页 Academic Journal of Pla Postgraduate Medical School
基金 海军后勤部科研项目(08-3306)
关键词 肺纤维化 内皮素受体拮抗剂 P物质 基质金属蛋白酶-2 pulmonary fibrosis endothelin receptor antagonist substance P matrix metalloproteinase-2
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参考文献10

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