红景天苷对力竭大鼠心肌细胞凋亡通路的影响

The effects of salidroside on the apoptosis pathway of myocardial cells in acute exhausted rats

目的:探讨红景天苷(Sal)能否通过改善心肌缺血,调控心肌细胞死亡受体和线粒体介导的凋亡途径相关蛋白,减少心肌细胞凋亡,发挥对力竭心脏的保护作用。方法:雄性SD大鼠,随机分为4组(n=6):对照组(Con)、力竭组(EE)、低剂量和高剂量Sal预处理力竭组(SLE、SHE)。分别给予Sal 15、30 mg/(kg·d)或生理盐水(3 ml/(kg·d))腹腔注射15 d。Con组不进行游泳训练,EE组、SLE组、SHE组于腹腔给药结束后次日参照Thomas力竭标准,一次性游泳运动至力竭。力竭运动结束后即刻麻醉取血和心脏,观测心肌缺血缺氧面积和心肌细胞凋亡指数(AI),测定血清中缺血修饰清蛋白(IMA)、心肌肌钙蛋白I(c Tn I)、脑钠肽(BNP)和心肌细胞Bcl-2相关的X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)的含量及心肌TNF受体超家族成员6 (Fas)、细胞色素C(Cyto-C)、天冬氨酸蛋白水解酶-3(Caspase-3)、天冬氨酸蛋白水解酶-8(Caspase-8)、天冬氨酸蛋白水解酶-9(Caspase-9)的表达情况。结果:与Con组比较,EE组大鼠心肌缺血缺氧面积、血清IMA、c Tn I、BNP含量、AI和Bax水平、心脏Fas、Cyto-C、Caspase-3、Caspase-8、Caspase-9蛋白表达均显著增加(P<0.01),心肌Bcl-2表达水平明显降低(P<0.01);与EE组比较,Sal显著改善力竭大鼠心肌缺血缺氧面积、明显降低力竭大鼠血清IMA、c Tn I、BNP含量和AI、Bax水平及心肌Fas、Cyto-C、Caspase-3、Caspase-8、Caspase-9的蛋白表达(P <0.01),明显提高心肌Bcl-2表达水平(P <0.01)。结论:红景天苷可通过改善心肌缺血,以及抑制死亡受体和线粒体凋亡通路相关蛋白Fas、Cyto-C、Caspase-3、Caspase-8、Caspase-9的表达,减少心肌细胞凋亡,从而发挥对力竭心脏的保护作用。

Objective: To investigate whether salidroside( Sal) plays a part in protecting myocardial cell through reducing the myocardial ischemia and the apoptosis pathway of both death receptors and mitochondria in acute exhausted rats. Methods: Male SD rats were randomly divided into 4 groups( n = 6): control group( Con),acute exhaustive swimming group( EE),low-dose and highdose Sal pre-treatment exhaustive swimming group( SLE,SHE). Rats were treated with Sal solution( 15 or 30 mg/( kg · d)) or0. 9% Na Cl( 3 ml/( kg·d)) by intraperitoneal injection for 15 d,respectively. The Con group did not carry out swimming training.The next day after the end of intraperitoneal administration,the rats in EE,SLE and SHE group were forced to swim until they were exhausted followed the standard of Thomas. After the end of exhaustive exercise,the rats were anesthetized and the blood samples and hearts were collected immediately. The myocardial ischemia and hypoxia area and myocardial apoptosis index( AI) were also observed.Serum ischemia modified albumin( IMA),cardiac troponin I( c Tn I),brain natriuretic peptide( BNP) and myocardial cell Bcl-2-associated X protein( Bax),B-cell lymphoma-2( Bcl-2) were determined. The expressions of myocardial TNF receptor superfamily member 6( Fas),cytochrome C( Cyto-c),aspartate proteolytic enzyme-3( Caspase-3),aspartate proteolytic enzyme-8( Caspase-8),and aspartate proteolytic enzyme-9( Caspase-9) were detected. Results: Compared with the Con group,the myocardial ischemia and hypoxia area in EE group was increased significantly. The serum levels of IMA,c Tn I and BNP,AI and Bax levels and cardiac Fas,Cyto-C,Caspase-3,Caspase-8 and Caspase-9 protein expressions of EE group were also increased significantly( P<0. 01),while the protein expression of Bcl-2 in cardiac tissues was decreased significantly( P<0. 01). Compared with the EE group,the myocardial ischemia and hypoxia area,serum levels of IMA,c Tn I and BNP,AI and Bax levels,and the protein expressions of cardiac Fas,Cyto-C,Caspase-3,Caspase-8 and Caspase-9 in Sal group were all decreased significantly( P<0. 01). while the protein expression of cardiac Bcl-2 in Sal group were increased significantly( P<0. 01). Conclusion: Sal plays a role in protecting myocardial cell through reducing the myocardial ischemia and inhibiting myocardial cell apoptosis in exhaustive exercise rats. The mechanism of reducing myocardial cell apoptosis may be related to inhibiting the expressions of Fas,Cyto-C,Caspase-3,Caspase-8,Caspase-9 and increasing the expression of Bcl-2.