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升降散对脓毒症大鼠心肌p38MAPK蛋白磷酸化水平的影响

  • 摘要: 目的:探讨升降散保护脓毒症心肌损伤的分子机制。方法:将雄性成年SD大鼠随机分为正常组、模型组、升降散组和p38抑制组。采用盲肠结扎穿孔术(CLP)制备脓毒症大鼠模型,造模后4、8、12、24 h进行观察。升降散组和p38抑制组大鼠分别于造模前2 h给予升降散灌胃和SB203580皮下注射。留取腹主动脉血标本和心脏组织作相关检测。观察和检测各时间点大鼠死亡率、血清心肌肌钙蛋白I(cTnI)、 B型利钠肽(BNP)、白介素-6(IL-6)水平以及心肌p-p38MAPK蛋白、p-p38MAPK mRNA、IL-6 mRNA的表达。结果:模型组大鼠24 h死亡率25%,升降散组、p38抑制组大鼠死亡率均为15%,组间差异无统计学意义。模型组大鼠血清cTnI、BNP升高;升降散组cTnI造模后8、12、24 h较模型组改善(P<0.001),BNP造模后4、12、24 h较模型组改善(P<0.05)。升降散组和p38抑制组cTnI、BNP造模后各时间点差异无统计学意义。模型组大鼠血清IL-6升高,升降散组各时间点IL-6改善(P<0.001)。模型组大鼠心肌各时间点p-p38MAPK蛋白水平升高,升降散组各时间点p-p38MAPK蛋白水平均改善(P<0.05)。模型组大鼠心肌p-p38MAPK mRNA表达升高,升降散组p-p38MAPK mRNA在8、12、24 h改善(P<0.05)。模型组大鼠心肌IL-6 mRNA升高,升降散组和p38抑制组造模后4、8、12 h均改善(P<0.05),升降散组IL-6 mRNA造模后12 h下降优于p38抑制组(P<0.05)。结论:升降散可有效降低脓毒症早期大鼠血清cTnI和BNP。升降散改善脓毒症心肌损伤可能与其下调脓毒症早期大鼠心肌p-p38MAPK蛋白水平,降低p-p38MAPK mRNA、IL-6 mRNA表达,从而抑制过度炎症反应有关。

     

    Abstract: Objective:To study the molecular mechanism of myocardial injury induced by traditional Chinese medicine Shengjiangsan. Methods:Male adult SD rats were randomly divided into normal group, model group, Shengjiangsan group and the p38 inhibitor group. By cecal ligation and puncture (CLP) of rat model of sepsis, the rat were observed at 4,8,12, and 24 h after operation. Shengjiangsan group and p38 inhibited rats respectively filled the stomach and subcutaneous injected the SB203580 in preoperative 2 h before giving Shengjiangsan. Blood samples from abdominal aortic were collected and heart tissue were detected. Observation and detection of each time node: mortality rate of rats, serum cTnI, BNP, IL-6 levels, myocardial p-p38MAPK protein, p-p38MAPK mRNA, IL-6 mRNA expression. Results:Model group has the 25% of mortality rates, while the Shengjiangsan group and the p38 inhibitor group both were 15%, which had no statistical significance. The cTnI and BNP were increased in model group, while the cTnI of 8 h, 12 h and 24 h in Shengjiangsan group were both improved (P<0.001), and the BNP of 4 h,12 h, and 24 h were all improved after BNP(P<0.05), but the difference between Shengjiangsan group and the p38 inhibitor group has no statistical significance in every time node. The IL-6 level in the model group has been higher and while in the Shengjiangsan group it has been decreased in every time node (P<0.001). The p-p38MARK protein level in model group grows higher, while the pp38MARK protein level in every time node of Shengjiangsan group has improved(P<0.05). The expression of p-p38MARK mRNA has all improved in the 8 h,12 h, and 24 h of Shengjiangsan group (P<0.05). The cardiac muscle Il-6 mRNA has improved in model group, while Shengjiangsan group and p38 inhibitor group of 4 h, 8 h, and 12 h has both improved (P<0.05), and the IL-6 mRNA become lower in the 12 h of Shengjiangsan group then of the p38 inhibitor group (P<0.05). Conclusions:Shengjiangsan can effectively reduce serum cTnI and BNP of the early sepsis rat. The molecular mechanism of that Shengjiangsan improved myocardial injury in sepsis may be related to the regulation of sepsis early rat by reduction of the myocardial p-p38MAPK protein level and the expression of p-p38MAPK mRNA and IL-6 mRNA, and also related to the inhibition the excessive inflammatory reaction.

     

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