目的探讨丹参酮ⅡA对脓毒症大鼠心肌凋亡的保护作用。方法采用盲肠结扎穿孔术制备脓毒症大鼠模型(CLP)，给予丹参酮ⅡA(TanⅡA)处理，于治疗12h后，取心肌组织测定Na+-K+-ATP酶(Na+-K+-ATPase)和超氧化物歧化酶(SOD)活性，肿瘤坏死因子-α、白介素-1β(IL-1β)、钙(Ca2+)和丙二醛(MDA)含量、细胞凋亡指数(AI)以及Bcl-2、Bax、Fas、caspase-3、calcincurin的蛋白水平。结果①与假手术组相比，脓毒症大鼠心肌肿瘤坏死因子-α、丙二醛、白介素-1β和Ca2+含量升高(P<0.05)，Na+-K+-ATPase和SOD活性降低(P<0.05);丹参酮ⅡA治疗后可改善脓毒症大鼠的以上异常。②与假手术组相比，脓毒症大鼠心肌细胞凋亡指数升高(P<0.05)，丹参酮ⅡA治疗后可降低脓毒症大鼠心肌细胞凋亡指数(P<0.05)。③与假手术组相比，脓毒症大鼠心肌细胞Bax、fas、calcincurin以及caspase-3的蛋白表达水平上升(P<0.05)，Bcl-2的蛋白表达水平下降(P<0.05)，且丹参酮ⅡA可使上述5种蛋白表达水平部分恢复(P<0.05)。结论丹参酮ⅡA对脓毒症大鼠心肌凋亡具有保护作用，可能通过降低心脏炎性水平、氧化应激、减轻钙超载，并能部分改善脓毒症大鼠凋亡基因(Bax、Bcl-2、Fas和caspases-3)以及钙调神经磷酸酶的异常表达实现。
Abstract
OBJECTIVE To explore the effect of tanshinone ⅡA(Tan ⅡA) on the myocardial apoptosis in rats with sepsis. METHODS The sepsis rat model was established by cecal ligation and puncture operation (CLP),and the Tan ⅡA was given for 12 consecutive hours. Then,the following indices were measured such as the activities of Na+-K+-ATPase and SOD,the contents of TNF-α,IL-1β,calcium,MDA,apoptotic index and the protein level of Bcl-2,Bax,Fas,caspase-3,calcincurin in myocardial. RESULTS ① Compared with sham group,CLP treatment can result in decreased myocardial activities of Na+-K+-ATPase and SOD,elevated the contents of IL-1β,calcium,MDA (P<0.05); Tan ⅡA treatment can improve the above aberrant indices . ②Compared with sham group,CLP treatment can elevated the myocardial apoptotic index (P<0.05),and Tan ⅡA treatment can decrease the elevation of apoptotic index by CLP treatment (P<0.05); ③Compared with sham group,the protein level of Bax,Fas,caspase-3 and calcincurin significantly increased,and protein level of Bcl-2 decreased (P<0.05) in CLP group,and Tan ⅡA treatment can improve exceptional expression of the above proteins(P<0.05). CONCLUSION Tanshinone ⅡA shows a protective effect on the myocardial apoptosis in septic rats maybe by depressing inflammatory infiltration and oxidative stress reaction,relieving calcium overload and partly improving the exceptional expression of the proteins such as Bax,Bcl-2,Fas,caspases-3 and calcincurin.
关键词
丹参酮ⅡA /
脓毒症 /
心肌凋亡
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Key words
tanshinone ⅡA /
sepsis /
myocardial apoptosis
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中图分类号：
R965
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参考文献
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脚注
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基金
国家自然科学基金资助项目(81202825)；湖北省自然科学基金资助项目(2011CDB196)
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