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硫氮卓酮对慢性低O2高CO2大鼠肺动脉压力和结构型一氧化氮合酶及其基因表达的影响

Effect of diltiazem on pulmonary arterial pressure and ceNOS mRNA expression in pulmonary arteries in chronic hypoxic hypercapnic rats

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【作者】 王良兴陈少贤徐正衸喻林升王群姬谢于鹏陈彦凡王卫张洪勤

【Author】 WANG Liang-xing,CHEN Shao-xian, XU Zheng-jie, YU Lin-sheng, WANG Qun-ji, XIE Yu-peng, CHEN Yan-fan, WANG Wei, ZHANG Hong-qin (Institute of Cor Pulmonale,Wenzhou Medical College,Wenzhou 325000, China)

【机构】 温州医学院附属第一医院呼吸内科肺心病研究室肺心

【摘要】 目的 :探讨硫氮卓酮对慢性低O2 高CO2 大鼠肺动脉压力的影响及其作用机制。方法 :将Sprague -Dawley大鼠分为正常对照组 (A组 ) ,四周低O2 高CO2 组 (B组 ) ,四周低O2 高CO2 +硫氮卓酮组 (C组 ) ,采用透射电镜、图像分析、免疫组化、原位杂交等方法 ,研究硫氮卓酮对慢性低O2 高CO2 大鼠肺动脉平均压 (mPAP)、颈动脉平均压 (mCAP)及肺动脉显微和超微结构、肺动脉结构型一氧化氮合酶 (ceNOS)及其基因表达的影响。结果 :①B组肺动脉平均压 (mPAP)明显高于A组 (P <0 0 1) ,C组mPAP明显低于B组 (P <0 0 1) ,A组和B组mCAP无明显差异 (P >0 0 5 ) ,C组mCAP低于B组 (P <0 0 1) ;②光镜下 ,肺细小动脉管壁面积 /管总面积比值 (WA/TA)C组明显低于B组(P <0 0 1) ;电镜下 ,C组大鼠肺细小动脉内皮损伤、中膜平滑肌细胞和胶原纤维增生明显轻于B组 ;③免疫组化见C组肺细小动脉ceNOS的平均吸光度值明显高于B组 (P <0 0 1) ;原位杂交发现C组肺细小动脉ceNOSmRNA平均吸光度值明显高于B组 (P <0 0 1)。结论 :硫氮卓酮可抑制慢性低O2 高CO2 性肺动脉高压形成和肺血管结构重建 ,肺动脉ceNOS及其基因表达的增加为其重要作用机制 ,硫氮卓酮可能为治疗COPD、肺动脉高压伴高血压或室上性心律失常患者较为理想的药物。

【Abstract】 AIM: To investigate the effect of diltiazem on mean pulmonary arterial pressure(mPAP) and nitric oxide synthase(NOS) in arterioles in chronic hypoxic hypercapnic rats. METHODS: Twenty-four rats were randomly divided into three groups: control group(A),hypoxic hypercapnic group(B), hypoxic hypercapnia+ diltiazem group (C), constitutive endothelial NOS(ceNOS) were observed in arterioles of rats using the technique of immunohistochemistry,ceNOS mRNA were observed by the technique of in situ hybridization . RESULTS: (1)mPAP was significantly higher in rats of B group than that of A and C group( P< 0 01) Differences of mCAP were not significant between A group and B groups( P> 0 05),but mCAP was lower in rats of C group than that in B group.(2)Light microscopy showed WA/TA (vessel wall area/total area) was significantly lower in rats of C group than that of B group ( P< 0 01), electron microscopy showed that diltiazem inhibited the proliferation of smooth muscle cells and collageous fibers of pulmonary arterioles in chronic hypoxic hypercapnic rats.(3)Immunohistochemistry showed the average value of integral light density(LD) of ceNOS in pulmonary arterioles was significantly higher in rats of C group than that of B group( P< 0 01), in situ hybridization showed LD of ceNOS mRNA in pulmonary arterioles was significantly higher in rats of C group than that of B group( P <0.01). CONCLUSION: Diltiazem inhibited pulmonary hypertension, the proliferation of smooth muscle cells and collagenous fibers of pulmonary arterioles in chronic hypoxic hypercapnic rats by incresing the expression of ceNOS in pulmonary arterioles.

【基金】 浙江省自然科学基金资助项目 (No.3985 30 ) ;浙江省医药卫生优秀青年科技人才专项科研基金资助
  • 【文献出处】 中国病理生理杂志 ,Chinese Journal of Pathophysiology , 编辑部邮箱 ,2002年09期
  • 【分类号】R364.4
  • 【被引频次】1
  • 【下载频次】68
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