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丹参酮ⅡA通过调节PI3K/AKT通路对异丙肾上腺素诱导的<br />大鼠心肌肥厚及纤维化的影响

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摘要:

目的 研究丹参酮ⅡA对异丙肾上腺素诱导的大鼠心肌肥厚及纤维化的影响及对磷脂酰肌
醇-3激酶(PI3K)/蛋白激酶B(AKT)通路的调节作用。方法 72只大鼠随机分为空白对照组、模型组、
丹参酮ⅡA低、中、高剂量组及PI3K抑制剂组,共六组,每组各12只。按照5 mg/kg的剂量皮下注射异丙
肾上腺素建立心肌肥厚大鼠模型。丹参酮ⅡA低、中、高剂量组分别腹腔注射给予大鼠17.5 mg/kg、35
mg/kg、70 mg/kg的丹参酮ⅡA,PI3K抑制剂组尾静脉注射给予大鼠0.3 mg/kg的LY294002,1/d,连续给药
28 d。生物机能实验系统测定大鼠左心室收缩压(LVSP)、左心室舒张末期压力(LVEDP)及左心室内
压最大变化速率(±dp/dtmax)。计算大鼠心脏质量及心脏指数,酶联免疫吸附法(ELISA)检测大鼠
心肌组织Ⅰ型及Ⅲ型胶原蛋白水平,苏木精-伊红(HE)染色和Masson染色对大鼠心肌组织进行病理学
检查。免疫印迹法(Western blot)检测大鼠心肌组织PI3K、p-PI3K、AKT、p-AKT蛋白水平。结果 与
空白对照组比较,模型组大鼠LVEDP、心脏质量、心脏指数、Ⅰ型及Ⅲ型胶原蛋白、心肌组织p-PI3K及
p-AKT水平显著升高(P<0.05),LVSP及±dp/dtmax显著降低(P<0.05);与模型组比较,丹参酮ⅡA
各剂量组及PI3K抑制剂组大鼠LVEDP、心脏质量、心脏指数、Ⅰ型及Ⅲ型胶原蛋白、心肌组织p-PI3K及
p-AKT水平显著降低(P<0.05),LVSP及±dp/dtmax显著升高(P<0.05)。结论 丹参酮ⅡA能够显著
改善异丙肾上腺素诱导的心肌肥厚大鼠血流动力学变化,抑制心肌纤维化进展及心肌组织病理改变,其
机制可能与调节PI3K及AKT信号通路有关。

Abstract:

Objective To study the influence of tanshinone ⅡA on myocardial hypertrophy and myocardial
fibrosis induced by isoproterenol and its regulating effect on phosphatidylinositol 3-kinase (PI3K)/ protein kinase
B (AKT) pathway in rats. Methods All rats (n=72) were randomly divided into blank control group, model group,
low-dose, mid-dose and highe-dose tanshinone ⅡA groups, and PI3K inhibitor group (each n=12). The rat model
of myocardial hypertrophy was established through subcutaneous injection of isoproterenol (5 mg/kg). The low-dose,
mid-dose and highe-dose tanshinone ⅡA groups were, respectively, given injection of intraperitoneally tanshinone
ⅡA (17.5 mg/kg, 35 mg/kg, 70 mg/kg). The PI3K inhibitor group was given injection of LY294002 (0.3 mg/kg) in
caudal vein, all injections were one a day for 28 d. The left ventricular systolic pressure ((LVSP), left ventricular
end-diastolic pressure (LVEDP) and the maximum change rate of left ventricular pressure (±dp/dtmax) were
detected by using biological function experiment system. The cardiac mass and cardiac index (CI) were calculated,
and levels of type Ⅰ and type Ⅲ collagens in rat myocardium were detected byusing enzyme-linked immunosorbent
assay (ELISA). The pathological changes of rat myocardial tissue were examined after hematoxylin-eosin (HE)
staining and Masson staining. The proteinlevels of PI3K, p-PI3K, AKT and p-AKT in myocardial tissue were
detected by using Western blotting assay. Results Compared with blank control group, LVEDP, cardiac mass, CI,
levels of type Ⅰ and type Ⅲ collagens and levels of PI3K, p-PI3K, AKT and p-AKT in myocardial tissue increased
significantly, and LVSP and ±dp/dtmax decreased significantly in model group (P<0.05). Compared with model
group, LVEDP, cardiac mass, CI, levels of type Ⅰ and type Ⅲ collagens and levels of PI3K, p-PI3K, AKT and
p-AKT in myocardial tissue decreased significantly, and LVSP and ±dp/dtmax increased significantly in low-dose,
mid-dose and highe-dose tanshinone ⅡA groups and PI3K inhibitor group (P<0.05). Conclusion Tanshinone ⅡA can significantly improve hemodynamic changes and inhibit myocardial fibrosis progression and myocardial
pathological changes in rats with isoproterenol-induced myocardial hypertrophy, and the mechanism may be related
to the regulation of PI3K and AKT signaling pathway.

基金项目:

国家自然科学基金项目(81700215);广东省中医药局
科研课题(20191211)

参考文献:

  • 2008

  • 1

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