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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Cocaine downregulates cardiac SERCA2a and depresses myocardial function in the murine model.
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Cocaine downregulates cardiac SERCA2a and depresses myocardial function in the murine model.

机译：可卡因在鼠模型中下调心脏SERCA2a并降低心肌功能。

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摘要

Cocaine has been shown to depress myocardial function, which may be linked to abnormal Ca2+ handling by the sarcoplasmic reticulum (SR). To examine whether cocaine affects Ca(2+)-handling proteins and myocardial performance, we injected BALB/c mice with cocaine daily (30 mg/kg, i.p.) for 14 d. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) levels, phospholamban (PLB) protein levels, and hemodynamic parameters were measured. After cocaine exposure, myocardial function was significantly decreased both in vivo and in vitro. Also, SERCA2a protein levels were significantly decreased in all cocaine-treated hearts (p < 0.05 compared with saline control). Normalized SERCA2a levels were 1.2 +/- 0.2 (densitometric units) in the cocaine groups (p < 0.05 compared with saline control). However, there was no statistical difference in PLB protein levels between the cocaine and the saline groups. In isolated papillary muscle studies, cocaine did not block the response to extracellular Ca2+ but it did prolong the relaxation time of the muscle. These results indicate that cocaine does not block extracellular Ca2+ entrance across the cell membrane, but that it decreases SERCA2a protein levels. In conclusion, our study demonstrates that cocaine decreases SERCA2a protein levels and depresses myocardial function.
机译：可卡因已显示可降低心肌功能，这可能与肌浆网（SR）异常处理Ca2 +有关。为了检查可卡因是否影响Ca（2+）处理蛋白和心肌性能，我们每天向BALB / c小鼠注射可卡因（30 mg / kg，腹腔注射）14天。测量了肌质网Ca（2 +）-ATPase（SERCA2a）水平，phospholamban（PLB）蛋白水平和血液动力学参数。可卡因暴露后，体内和体外心肌功能均显着下降。此外，在所有可卡因治疗的心脏中，SERCA2a蛋白水平均显着降低（与盐水对照组相比，p <0.05）。可卡因组的标准化SERCA2a水平为1.2 +/- 0.2（光密度单位）（与盐水对照组相比，p <0.05）。然而，可卡因和生理盐水组之间的PLB蛋白水平没有统计学差异。在孤立的乳头肌研究中，可卡因并未阻止对细胞外Ca2 +的反应，但确实延长了肌肉的松弛时间。这些结果表明可卡因不会阻止细胞外Ca2 +进入细胞膜，但会降低SERCA2a蛋白水平。总之，我们的研究表明可卡因降低了SERCA2a蛋白水平并降低了心肌功能。

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