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二氧化硫恢复异丙肾上腺素诱导心肌损伤大鼠钙稳态紊乱。

Sulfur dioxide restores calcium homeostasis disturbance in rat with isoproterenol-induced myocardial injury.

机构信息

Department of Pediatrics, Peking University First Hospital, Beijing, China.

出版信息

Histol Histopathol. 2012 Sep;27(9):1219-26. doi: 10.14670/HH-27.1219.

DOI:10.14670/HH-27.1219
PMID:22806909
Abstract

BACKGROUNDS

sulfur dioxide (SO₂) could relieve isoproterenol (ISO)-induced myocardial injury, while the mechanism is unclear. This study aims to explore whether the protective effect of SO₂ on ISO-induced myocardial injury was mediated by the restoration of calcium homeostasis disturbance in cardiomyocyte.

METHODS AND RESULTS

Rats were randomly divided into four groups: ISO group, ISO+SO₂ group, control group and SO₂ group. Content of Ca²⁺ in H9c2 cells was assayed using confocal microscope, and cardiac function parameters were measured by echocardiography. Plasma biochemical values and myocardial ultra-structure changes were measured. Meanwhile, the activity, protein and gene levels of sarcoplasmic reticulum Ca²⁺ ATPase (SERCA), and protein and phosphorylation of phospholamban (PLN) were detected. We found SO₂ derivatives could restore the decreased cardiac function, the abnormal lactate dehydrogenase, creatine kinase, alpha-hydroxybutyrate dehydrogenase, potassium, calcium, blood urea nitrogen and the damaged myocardial ultra-structure in rats, and regulate the increased Ca²⁺ content in H9c2 induced by ISO. In addition, compared with ISO group, the decreased activities, protein and mRNA level of SERCA, as well as the decreased protein phosphorylation level of PLN in myocardial tissues were increased in ISO+SO₂ group.

CONCLUSION

SO₂ derivatives might relieve calcium overload in association with the upregulating expression of SERCA and p-PLN/PLN by myocardial tissues in rats with ISO-induced myocardial injury.

摘要

背景

二氧化硫(SO₂)可缓解异丙肾上腺素(ISO)诱导的心肌损伤,但机制尚不清楚。本研究旨在探讨 SO₂对 ISO 诱导的心肌损伤的保护作用是否通过恢复心肌细胞钙稳态紊乱来介导。

方法和结果

大鼠随机分为四组:ISO 组、ISO+SO₂组、对照组和 SO₂组。使用共聚焦显微镜测定 H9c2 细胞内 Ca²⁺含量,通过超声心动图测量心功能参数。测定血浆生化值和心肌超微结构变化。同时,检测肌浆网 Ca²⁺ATP 酶(SERCA)的活性、蛋白和基因水平,以及磷蛋白(PLN)的蛋白和磷酸化水平。我们发现 SO₂衍生物可恢复 ISO 降低的大鼠心功能、异常的乳酸脱氢酶、肌酸激酶、α-羟丁酸脱氢酶、钾、钙、血尿素氮和受损的心肌超微结构,并调节 ISO 诱导的 H9c2 中 Ca²⁺含量的增加。此外,与 ISO 组相比,ISO+SO₂组心肌组织中 SERCA 的活性、蛋白和 mRNA 水平降低,PLN 的蛋白磷酸化水平降低。

结论

SO₂衍生物可能通过上调 ISO 诱导的心肌损伤大鼠心肌组织中 SERCA 和 p-PLN/PLN 的表达来缓解钙超载。

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