丹参酮ⅡA对压力负荷增加的大鼠TNF-α表达的影响

Effect of Tanshinone ⅡA on TNF-α expression with pressure overload

目的观察TNF-α在压力负荷增加大鼠血清中的表达,并探讨其对心肌纤维化的作用机制。方法 32只成年雄性SD大鼠,随机分成四组(n=8),假手术组(Sham组)、模型组(Model组)、Tan II A组(Tan II A组,20 mg.kg-1.d-1)及阳性对照药物卡托普利组(Captopril组,100 mg.kg-1.d-1)。除Sham组外,其余3组大鼠均行肾上方腹主动脉缩窄术制备压力负荷增加心肌纤维化模型,Sham组仅分离腹主动脉而不结扎。术后4周成功造模并开始给药,疗程为4周。8周后检测左室重量指数、心肌组织病理学、心肌羟脯氨酸(HYP)含量、血清TNF-α蛋白的含量。结果与Model组比较,Tan II A组能明显抑制心肌纤维化大鼠心肌组织的病理改变,降低心肌肥厚指数、心肌羟脯氨酸含量以及血清TNF-α蛋白浓度(P<0.01)。结论压力负荷增加大鼠血清TNF-α蛋白表达明显升高,表明促炎细胞因子TNF-α在压力负荷增加大鼠心肌纤维化中起着重要的作用;TanII A对心肌纤维化的保护作用可能部分与下调促炎细胞因子表达有关。

Objeαive To observe the expression of TNF-α in rat with pressure overload, and to explore the mechanism of Tanshinone II A （ Tan II A） on myocardial fibrosis. Methods Twenty-four Sprague-Dawley（SD） rats induced by the ＇abdominal aorta constriαion prepara- tion were randomly assigned into following apporches （n = 8 ） ：Model group, Tan II A group （Tan 11 A group, 20 mg·kg-1·d-1 ）and positive captopril group（ captopril group, 100 mg·kg-1·d-1） , age matched SD sham operated group （n = 8 ）as control. The model of pressure overload-induced myocardial fibrosis was successfully established ＇after 4 weeks of operation. After four weeks of Tan [IA treat- ment, left ventricular mass index, histopathological, myocardial hydroxyproline content, serum tumor necrosis faαor-cx （ TNF-~x ） were meas- ured. Results Competed with model group ,Tan II A can significantly inhibit myocardial pathological changes, reduce cardiac hypertro- phy index and myocardial hydroxyproline content, downregulate serum and myocardial tissue of TNF-α protein content（ P 〈 0.01 ）. Con- clusions The expression of serum TNF-α protein was significantly increased in pressure overload rat, indicating that proinflammatory cy- tokine TNF-α plays an important role in myocardial fibrosis ;Tan Ⅱ A can improve cardiac fibrosis, and this effeα may be partly associat- ed with downregulation of the expression of proinflammatory cytokine.