PANAX QUINQUEFOLIUM SAPONINS REDUCE MYOCARDIAL HYPOXIA-REOXYGENATION INJURY BY INHIBITING EXCESSIVE ENDOPLASMIC RETICULUM STRESS
PANAX QUINQUEFOLIUM SAPONINS REDUCE MYOCARDIAL HYPOXIA-REOXYGENATION INJURY BY INHIBITING EXCESSIVE ENDOPLASMIC RETICULUM STRESS
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DOI：
10.1097/shk.0b013e31823f15c4
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发表时间：
2012-02-01
期刊：
影响因子：
3.1
通讯作者：
Liu, Xiu-Hua
中科院分区：
文献类型：
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作者：
Wang, Chen;Li, Yu-Zhen;Liu, Xiu-Hua
过度的内质网应激（ERS）破坏蛋白质翻译、蛋白质折叠和钙稳态，并可能导致缺血再灌注损伤。从西洋参茎叶中提取的皂苷对大鼠心肌缺血再灌注损伤具有保护作用，但对ERS的抑制是否有助于心脏保护尚不清楚。新生大鼠心肌细胞在PQS或载药存在下进行缺氧再氧化（H-R）。采用台盼蓝排除法、乳酸脱氢酶活性法和流式细胞术检测细胞损伤和凋亡情况。此外，采用逆转录聚合酶链反应和Western blotting检测ers相关蛋白葡萄糖调节蛋白78、钙调蛋白、CCAAT/增强子结合蛋白同源蛋白、caspase-12以及凋亡相关蛋白Bax和Bcl-2的mRNA和蛋白表达。我们证实PQS可以保护心肌细胞免受h - r诱导的损伤和凋亡细胞死亡。此外，PQS抑制h -r诱导的过度ERS，这可以通过降低caspase 12激活和降低葡萄糖调节蛋白78、钙调蛋白和CCAAT/增强子结合蛋白同源蛋白的过度表达来证明。上述结果表明，PQS可减轻心肌细胞H-R损伤，其作用机制可能与抑制H-R诱导的过多ERS有关。
Excessive endoplasmic reticulum stress (ERS) disrupts protein translation, protein folding, and calcium homeostasis and may contribute to ischemia-reperfusion injury. Saponins extracted from the stems and leaves of Panax quinquefolium (PQS) protect rat myocardium against ischemia-reperfusion injury, but it is not known if suppression of ERS contributes to cardioprotection. Neonatal rat cardiomyocytes were subjected to hypoxia-reoxygenation (H-R) in the presence of PQS or vehicle. Cell injury and apoptosis were assayed by trypan blue exclusion, lactate dehydrogenase activity, and flow cytometry. In addition, reverse transcriptase-polymerase chain reaction and Western blotting were used to examine mRNA and protein expression of the ERS-related proteins glucose-regulated protein 78, calreticulin, CCAAT/enhancer-binding protein homologous protein, and caspase-12, as well as the apoptosis-associated proteins Bax and Bcl-2. We confirmed that PQS protects cardiomyocytes from H-R-induced injury and apoptotic cell death. Furthermore, PQS suppressed H-R-induced excessive ERS, as evidenced by reduced caspase 12 activation and decreased glucose-regulated protein 78, calreticulin, and CCAAT/enhancer-binding protein homologous protein overexpression. These results indicated that PQS could alleviate H-R injury of cardiomyocytes, which would be probably related to inhibiting excessive ERS induced by H-R.