姜黄素对脂多糖诱导的心肌功能障碍小鼠PI3K-γ表达的影响

Effects of curcumin on the expression of PI3K-γ in mice with lipopolysaccharide induced myocardial dysfunction

摘要:

目的：探讨姜黄素（Curcumin）对脂多糖（lipopolysaccharide，LPS）诱导的脓毒症心肌功能障碍（sepsis induced myocardial dysfunction，SIMD）小鼠磷脂酰肌醇-3-激酶-γ（phosphoinositide-3-kinases-γ，PI3Kγ）表达的影响。方法：将60只雄性c57bl/6小鼠按随机数字表法随机分为正常对照组（Con组）、脓毒症组（Sep组）、姜黄素组（Cur组）和二甲基亚砜（DMSO）组，每组15只，Sep、DMSO和Cur组采用LPS 10 mg/kg 腹腔注射制备SIMD模型，造模30 min后，Cur组经腹腔注射200 mg/kg姜黄素，Con组和Sep组经腹腔注射等量生理盐水，DMSO组经腹腔注射等量DMSO。于给药后 6、12、24 h，各组小鼠经右颈动脉插管采用BL-410多功能监护仪监测血流动力学指标，包括左心室收缩压（left ventricular systolic pressure，LVSP）、左心室舒张末期压（left ventricular end-diastolic pressure，LVEDP）、左室内压力变化最大上升和下降速率（maximum rate of left ventricular pressure de－velopment and decay，LV±dp/dt-max）；HE染色观察心肌组织病理改变；ELISA 法检测小鼠血清中心肌肌钙蛋白Ⅰ（cardiac tro－ponin，CTnⅠ）和肿瘤坏死因子（tumor necrosis factor，TNF-α）含量的变化；Western blot检测心肌组织中PI3K－γ、p-akt蛋白的表达。结果：Cur组心脏血流动力学指标（LVSP、LVEDP 和LV±dp/dt-max）在各时间点与 Sep 组比较，均明显上升（P=0.000）；心肌组织的病理学改变与Sep 组相比，损伤明显减轻；心肌组织中PI3K－γ蛋白的表达量较 Sep 组明显下降，p-akt蛋白的表达量较 Sep组升高（P=0.000）；小鼠血清中CTnⅠ和TNF-α含量较sep组降低（P=0.000，P=0.000）。DMSO组与Sep组比较，各指标差异均无统计学意义（P=0.586）。结论：姜黄素对SIMD小鼠的心肌保护作用与抑制PI3K－γ蛋白的表达有关。

Abstract:

Objective：To investigate the effect of curcumin on expression of phosphoinositide-3-kinases-γ（PI3K-γ） in sepsis induced myocardial dysfunction（SIMD） mice． Methods：The 60 male c57bl/6 mice were randomly divided into control（Con），sepsis（Sep），curcumin（Cur） and DMSO groups（n=15 per group） by completely randomized digital table study. Mouse SIMD model was in－duced by intraperitoneal injection of 10 mg/kg lipopolysaccharide（LPS）. Mice in Cur group were injected with 200 mg/kg curcumin at 30 min after LPS administration；those in Con and Sep groups with an equal volume of sterile saline solution and those in DMSO group with an equal volume of DMSO． The left ventricular systolic pressure（LVSP），left ventricular end-diastolic pressure（LVEDP） as well as mximum rate of left ventricular pressure development and decay（LV±dp/dt-max） in various groups were monitored by BL-410 multiple monitor in the right carotid artery. Histopathological changes of cardiac muscles were observed by HE staining. The expression of cTnⅠ and TNF-α in serum was detected by ELISA and the expression of PI3K-γ and p-akt in cardiac muscles by Western blot． Results：Compared with those in Sep group，values of LVSP，LVEDP and LV±dp/dt-max at various time points were increased significantly（P=0.000），histopathological changes of cardiac muscles were relieved significantly，the expression levels of PI3K-γ in cardiac muscles were reduced significantly（P=0.000），the expression levels of p-akt protein were increased（P=0.000），and mouse serum cTnⅠ and TNF-α levels were decreased significantly（P=0.000，P=0.000） in Cur group. However，no significant difference was observed between the indexes in DMSO and Sep groups（P=0.586）． Conclusion：The protective effect of curcumin on cardiac muscles of SIMD mice is associated with the inhibition of PI3K-γ expression.