丹参酮ⅡA通过激活SDF-1/CXCR4轴对大鼠急性心肌梗死的保护作用  

Protective effect of tanshinoneⅡA on acute myocardial infarction in rats by activating SDF-1/CXCR4 axis

作　　者：唐志爱 郭世燕 黄建波 TANG Zhi-ai;GUO Shi-yan;HUANG Jian-bo(Department of Cardiovascular Medicine,Beijing Road Medical District,General Hospital of Xinjiang Military Region,Urumqi 830013,China)

机构地区：[1]新疆军区总医院北京路医疗区心血管内科,新疆乌鲁木齐830013

出　　处：《实用药物与临床》2020年第11期969-974,共6页Practical Pharmacy and Clinical Remedies

基　　金：新疆维吾尔自治区自然科学基金项目(2019D01C081)。

摘　　要：目的研究丹参酮ⅡA对急性心肌梗死大鼠的保护作用及机制。方法30只雄性SD大鼠随机分为5组:对照组,模型组,丹参酮ⅡA低、中、高剂量组,每组6只。采用结扎冠状动脉血管的方法建立急性心肌梗死大鼠模型。造模完成后,丹参酮ⅡA低、中、高剂量组分别按照20 ml/kg分别灌胃给予大鼠1 mg/ml、2 mg/ml、4 mg/ml的丹参酮ⅡA,对照组及模型组按照20 ml/kg灌胃给予生理盐水,连续给药21 d后,测定大鼠血清TNF-α、IL-6、IL-1β水平及血流动力学变化,实时定量PCR检测各组大鼠心肌组织中Bax、Bcl-2、Caspase-12和Caspase-3 mRNA的水平,苏木精-伊红染色法进行组织病理学检查,Western blot检测大鼠心肌组织SDF-1、CXCR4水平。结果连续21 d给予急性心肌梗死大鼠不同剂量的丹参酮ⅡA后,与模型组相比,丹参酮ⅡA各剂量组急性心肌梗死大鼠体内TNF-α、IL-6、IL-1β水平,心肌组织Bax、Caspase-12和Caspase-3 mRNA水平均显著降低(P<0.05),Bcl-2水平显著升高(P<0.05),LVEDV、LVESV均显著降低(P<0.05),LVEF显著升高(P<0.05);组织病理学检查表明,丹参酮ⅡA能够显著改善急性心肌梗死大鼠组织病理学变化;Western blot结果表明,丹参酮ⅡA各剂量组大鼠心肌组织SDF-1、CXCR4水平显著升高(P<0.05)。结论丹参酮ⅡA能够抑制急性心肌梗死大鼠体内炎症反应,调节心肌细胞凋亡相关基因的表达,从而发挥对急性心肌梗死大鼠的保护作用,其机制可能与激活急性心肌梗死大鼠体内SDF-1/CXCR4轴有关。Objective To study the protective effect and mechanism of tanshinoneⅡA on acute myocardial infarction in rats.Methods Thirty male SD rats were randomly divided into 5 groups with 6 rats in each group:control group,model group,low-,middle-and high-dose tanshinoneⅡA groups.The rat model of acute myocardial infarction was established by ligation of coronary arteries.After the establishment of the model,the low-,middle-and high-dose of tanshinoneⅡA groups were given tanshinoneⅡA of 1 mg/ml,2 mg/ml and 4 mg/ml respectively according to 20 ml/kg,while the control group and model group were given normal saline according to 20ml/kg.After continuous administration for 21 days,the levels of serum TNF-α,IL-6 and IL-1βand hemodynamic changes were measured.Real-time quantitative PCR was used to detect the levels of Bax,Bcl-2,Caspase-12 and Caspase-3 mRNA in myocardial tissue,and hematoxylin-eosin staining was used for histopathological examination.Western blot was used to detect the levels of SDF-1 and CXCR4 in myocardial tissue.Results After administration of tanshinoneⅡA for 21 days,the levels of TNF-α,IL-6 and IL-1βin the rats,and the levels of Bax,Caspase-12 and Caspase-3 mRNA in myocardium of rats with acute myocardial infarction were significantly lower than those in the model group(P<0.05),while the level of Bcl-2 was significantly increased(P<0.05);LVEDV and LVESV were significantly decreased(P<0.05),and LVEF was significantly increased(P<0.05).Histopathological examination showed that tanshinoneⅡA could significantly improve the histopathological changes of rats with acute myocardial infarction.The results of Western blot showed that the levels of SDF-1 and CXCR4 in myocardial tissue of rats in all dose groups of tanshinoneⅡA were significantly increased(P<0.05).Conclusion TanshinoneⅡA can inhibit the inflammatory reaction in rats with acute myocardial infarction and regulate the expression of cardiomyocyte apoptosis-related genes,so as to protect rats from acute myocardial infarction.The mechanis

关 键 词：丹参酮ⅡA 急性心肌梗死 SDF-1/CXCR4轴 

分 类 号：R285.5[医药卫生—中药学]