心肌内向整流钾通道激动剂抑制异丙肾上腺素所致大鼠心室重构

发布时间：2018-05-30 20:33

本文选题：内向整流钾通道 + 异丙肾上腺素　；参考：《中国病理生理杂志》2017年03期

【摘要】：目的:观察和探讨内向整流钾通道(Ⅰ_(K1))激动剂盐酸扎考必利(zacopride,Zac)对异丙肾上腺素(isoproterenol,Iso)所致心室重构的影响及作用机制。方法:SD大鼠随机分为正常对照组、Iso模型组、Zac干预组、Zac+氯喹干预组和卡托普利阳性对照组。腹腔注射异丙肾上腺素3 mg/kg,每天1次,连续给药10 d,观测各组全心质量/体质量比和左心室质量/体质量比。用全细胞膜片钳技术检测大鼠心室肌细胞电压门控钙电流(Ⅰ_(Ca-L))、静息膜电位(RMP)及动作电位时程(APD)的变化。选用新生1~3 d的SD乳鼠,用0.08%胰蛋白酶和0.04%Ⅱ型胶原酶消化心脏组织,经差速贴壁法和5-溴脱氧尿嘧啶核苷纯化心肌细胞后随机分成正常对照组、Iso模型组、Zac干预组、Zac+BaCl_2干预组和Zac+氯喹干预组,培养24 h后用激光共聚焦显微镜检测心肌细胞内游离钙离子浓度。结果:Iso模型组与正常对照组比较,全心肥厚指数、左心室肥厚指数明显增加,膜片钳结果提示RMP减小APD明显延长;Zac干预组明显抑制心肌肥大,并增大RMP,缩短APD。同时应用低剂量Ⅰ_(K1)抑制剂氯喹可明显抑制Zac的抗心室重构作用,并逆转Zac对RMP和APD影响。在乳鼠心肌细胞,Iso可使细胞表面积增大,细胞内[Ca~(2+)]_i增高;Zac干预后细胞形态恢复至正常或接近正常水平,并显著减轻钙超载。Ⅰ_(K1)阻断剂BaCl_2和氯喹可阻断Zac的效应。结论:Ⅰ_(K1)选择性激动剂Zac明显抑制异丙肾上腺素所致的心室重构,其机制可能为增强Ⅰ_(K1),进而增大RMP,缩短APD,从而阻断心肌细胞内钙超载依赖的信号通路。
[Abstract]:Aim: to investigate the effect and mechanism of zacopridee hydrochloride (Zacacopridea), an inward rectifier potassium channel (I) agonist, on ventricular remodeling induced by isoproterenolium Iso. Methods the rats were randomly divided into normal control group (Iso model group) and captopril positive control group (control group). Isoproterenol was injected intraperitoneally at a dose of 3 mg / kg once a day for 10 days. The whole heart mass / body mass ratio and left ventricular mass / body mass ratio were measured. Whole-cell patch clamp technique was used to detect the changes of voltage-gated calcium current (I), resting membrane potential (RMP) and action potential duration (APD) in rat ventricular myocytes. Neonatal SD rats of 1 and 3 days were used to digest heart tissue with 0.08% trypsin and 0.04% collagenase. Myocardial cells were purified by differential adherent method and 5-bromodeoxyuridine (5-bromodeoxyuridine). They were randomly divided into two groups: normal control group, Iso model group, Zac BaCl_2 intervention group and Zac chloroquine intervention group. The intracellular free calcium concentration was measured by confocal laser microscope after 24 h culture. Results compared with the normal control group, the whole heart hypertrophy index and left ventricular hypertrophy index were significantly increased in the control group. The results of patch clamp showed that the decrease of APD in RMP group significantly inhibited myocardial hypertrophy, increased APD and shortened APD. At the same time, chloroquine, a low dose of I / L K1) inhibitor, significantly inhibited the effects of Zac on ventricular remodeling and reversed the effects of Zac on RMP and APD. In neonatal rat cardiomyocytes treated with Iso, the surface area of cells was increased, and the intracellular [Ca~(2] increased. After the intervention of Zac, the morphology of the cells returned to normal or close to normal level, and the calcium overload was significantly alleviated. I. the effects of BaCl_2 and chloroquine, a blocker, could block the effect of Zac. Conclusion: Zac, a selective agonist, significantly inhibits ventricular remodeling induced by isoproterenol. The mechanism may be to increase the number of RMPs and shorten them, thus blocking the calcium-dependent signaling pathway in cardiomyocytes.
【作者单位】：山西医科大学病理生理学教研室;山西医科大学生理学教研室;山西省儿童医院;
【基金】：国家自然科学基金资助项目(No.31200864) 山西省回国留学人员科研资助项目(No.2016-059)
【分类号】：R96

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