石斛碱对心肌缺血再灌注损伤大鼠的凋亡抑制作用  

Inhibitory effects of dendrobine on apoptosis in rats with myocardial ischemia-reperfusion injury

作　　者：罗向红 李丽娟 赵婷 王孝萍 周伟 李娜 余红艳 张学森 LUO Xiang-hong;LI Li-juan;ZHAO Ting;WANG Xiao-ping;ZHOU Wei;LI Na;YU Hong-yan;ZHANG Xue-sen(Department of Cardiology,Wuzhong People’s Hospital,Wuzhong 751100,China;Department of Orthopedics,Wuzhong People’s Hospital,Wuzhong 751100,China)

机构地区：[1]吴忠市人民医院心血管内科,宁夏吴忠751100 [2]吴忠市人民医院骨科,宁夏吴忠751100

出　　处：《中成药》2023年第6期1839-1844,共6页Chinese Traditional Patent Medicine

基　　金：宁夏自然科学基金资助项目(2021AAC03530,2022AAC03765)。

摘　　要：目的探讨石斛碱保护大鼠心肌缺血再灌注损伤的作用及对Bax/Cyt-C/caspase3凋亡信号通路的影响。方法将60只大鼠随机分为假手术组、模型组、复方丹参组(300 mg/kg,阳性对照)及石斛碱高、中、低剂量组(40、20、10 mg/kg),每组10只,每天灌胃给药1次,连续14 d。末次给药后24 h,采用左冠状动脉前降支结扎和再通法复制大鼠心肌缺血再灌注损伤模型。建模成功后记录大鼠平均动脉压(MAP)、左心室舒张末期压(LVEDP)、左室收缩压(LVSP)、左室内压最大上升和下降速率(LV dP/d t max/dP/d t min)。采用生化法检测大鼠血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)水平,TTC法检测大鼠心肌梗死面积,HE染色观察大鼠心肌组织病理形态学变化,RT-PCR和Western blot法检测大鼠心肌组织Bax、Bcl-2、Cyt-C、caspase3 mRNA和蛋白表达。结果与模型组比较,石斛碱高剂量组大鼠MAP、LVSP、LV dP/d t max及LV dP/d t min升高(P<0.01),LVEDP下降(P<0.01);血清LDH、CK、CK-MB水平降低(P<0.01);心肌梗死面积减少(P<0.01);心肌纤维排列较为有序,细胞间偶见炎性细胞分布,部分细胞结构缺损,仍有断裂或萎缩现象;心肌组织Bax、Cyt-C、caspase3 mRNA和蛋白表达降低(P<0.01),Bcl-2 mRNA和蛋白表达升高(P<0.01)。结论石斛碱对心肌缺血再灌注损伤大鼠心脏具有保护作用,其作用机制与抑制Bax/Cyt-C/caspase3凋亡信号通路有关。AIM To investigate the protective effects of dendrobine on myocardial ischemia-reperfusion injury(MI/RI)in rats and their association with Bax/Cyt-C/caspase3 apoptosis signaling pathway.METHODS Sixty rats were randomly divided into the sham operation group,the model group,the compound salvia miltiorrhiza group(300 mg/kg,positive control)and high,medium and low dose groups of dendrobine(40,20 and 10 mg/kg),with 10 rats in each group,for corresponding oral drug administration once daily for 14 days.Twenty-four hours after the last feeding,the rat model of MI/RI was established by ligating and recanalizing the anterior descending branch of left coronary artery.After the successful modeling,all rats had their mean arterial pressure(MAP),left ventricular end diastolic pressure(LVEDP),left ventricular systolic pressure(LVSP)and the maximum rate of increase and decrease of left ventricular pressure(LV dP/d t max/dP/d t min)measured and recorded;their serum levels of lactate dehydrogenase(LDH),creatine kinase(CK)and creatine kinase isoenzyme(CK-MB)detected by biochemical method;their myocardial infarction area detected by TTC method;their pathological changes of myocardial tissue observed by HE staining method;and their mRNA and protein expressions of Bax,Bcl-2,Cyt-C and caspase3 detected by RT-PCR and Western blot.RESULTS Compared with the model group,the high-dose dendrobine group displayed increased MAP,LVSP,LV dP/d t max and LV dP/d t m in(P<0.01);decreased LVEDP(P<0.01);decreased levels of serum LDH,CK and CK-MB(P<0.01);decreased area of myocardial infarction(P<0.01);relatively orderly arrangement of myocardial fibers;occasional distribution of inflammatory cells among the cells;some structurally defective cells with fracture or atrophy;decreased mRNA and protein expressions of Bax,Cyt-C and caspase3(P<0.01);and increased mRNA and protein expressions of Bcl-2(P<0.01).CONCLUSION Dendrobine elicits protective effect on the hearts of MI/RI rats,and its mechanism is related to the inhibition of Bax/Cyt-C/caspase3 apopto

关 键 词：石斛碱 心肌缺血再灌注损伤 细胞凋亡 Bax/Cyt-C/caspase3信号通路 

分 类 号：R285.5[医药卫生—中药学]