埃他卡林对压力超负荷大鼠心室重构和血浆中PGI_2的影响  

Effects of iptakalim on pressure-overload induced cardiac remodeling and plasma PGI_2 content in rats

作　　者：高杉[1] 龙超良[2] 王汝欢[3] 汪海[2] 

机构地区：[1]安徽医科大学基础医学院药理学教研室抗炎免疫药理学省部共建教育部重点实验室,合肥230032 [2]军事医学科学院卫生学环境医学研究所心血管药物研究中心,北京100850 [3]北京赛德维康医药研究院,北京100039

出　　处：《中国应用生理学杂志》2011年第3期294-298,386,共6页Chinese Journal of Applied Physiology

基　　金：国家高技术研究发展计划(863计划)重大专项资助(2002AA2Z3137);国家重大新药创制科技重大专项(2009ZXD9301-002;2008ZXO09101-006);国家特需药品保密专项(2008ZXJ09004-018)

摘　　要：目的:观察埃他卡林(IPT)对压力超负荷大鼠心室重构的影响,探讨其保护作用与血浆中前列环素(PGI2)的关系。方法:SD大鼠经腹主动脉缩窄6周后诱导压力超负荷高血压模型,随机分为5组(n=9):①假手术组;②模型组;③IPT 3 mg/kg组(IPT3);④吲哚美辛2 mg/kg(Indo 2)组;⑤IPT 3mg/kg+吲哚美辛2 mg/kg(IPT 3+Indo 2)组。RM-6000八导生理记录仪记录血流动力学改变,称量计算心脏重量指数,HE染色和Masson’s染色观察心肌组织病理学改变,比色法检测心肌组织羟脯氨酸含量,放免法检测血浆中PGI2含量。结果:腹主动脉缩窄6周后,与假手术组相比,模型组大鼠出现了明显的高血流动力学状态和心室重构,血浆中PGI2含量也明显降低,而IPT 3 mg/kg实验治疗6周可明显改善上述变化。单用吲哚美辛可进一步恶化大鼠的高血流动力学状态和心室重构,合用IPT可明显改善高血流动力学状态和心肌纤维化,明显抑制血浆中PGI2含量的降低。结论:IPT可明显逆转腹主动脉缩窄/压力超负荷大鼠的心室重构,其机制可能与IPT作用于内皮细胞上的KATP通道,恢复内皮细胞的分泌功能增加PGI2的合成和分泌密切相关。Objective： To study the effects of iptakalim（lPr） on pressure-overload induced cardiac remedeling in rats, and investigate correlation between this protection effects and plasma PGI2 content. Method： The pressure-overload induced cardiac remodeling model was induced by abdominal aorta constriction for 6 weeks, and the rats were divided into 5 groups repectively： （1）sham group, （2）control group, （3）IPT 3 mg/kg group（IPT 3）, （4）indomethacin 2 mg/kg group （Indo 2）, （5）indomethacin 2 mg/kg ＋ IPT 3 mg/kg group（Indo 2＋ IPT 3）. RM- 6000 eight channel physiological recorder was used to record haemedynamics index, heart weight was weighed and the cardiac remodeling index was calculated, HE stain and Masson＇ s stain were employed to perform histological analysis, colorimetric method was used to detect the hydroxypreline content in cardiac tissue, radioimmunological method was used to measure the plasma PGI2 content. Results： After 42 days of aortic banding, the hyperdynamic circulation state, cardiac remodeling and decreased plasma PGI2 content were observed in the model group compared with those in the sham group, which were effectively reserved by treatment with IPT 3 mg/kg. Single-use indomethacin led to further deterioration of this pathophysiological changes, however, combination administration of IPT 3 mg/kg prevented these from worsening characteristic by ameliorating hyperdynamic circulation state and cardiac remodeling, augnent plasma PGI2 content. Conclusion： IPT can significantly reverse abdominal aorta binding/pressure-overload induced cardiac remodeling, its mechanism may contribute to binding KATP channel in endothelial cells, ameliorating endothelium cells function, augmenting PGI2 synthesis and secretion.

关 键 词：盐酸埃他卡林 心室重构 前列环素 吲哚美辛 

分 类 号：R-332[医药卫生]