p53信号通路在半枝莲总黄酮预处理大鼠心肌缺血再灌注损伤中的作用  

Role of p53 signaling pathway in myocardial ischemia/reperfusion injury in rats pretreated with Scutellaria barbata flavonoids

作　　者：于淼 李铁成 YU Miao;LI Tie-Cheng(Department of Anesthesiology,Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,Liaoning Province,China)

机构地区：[1]锦州医科大学附属第三医院麻醉科,辽宁锦州121000

出　　处：《中华老年多器官疾病杂志》2021年第7期538-543,共6页Chinese Journal of Multiple Organ Diseases in the Elderly

基　　金：辽宁省自然科学基金项目(20170540372)。

摘　　要：目的探讨半枝莲总黄酮(SBF)对心肌缺血/再灌注损伤(MI/RI)模型的保护作用及相关机制。方法将50只SD雌性大鼠按照随机数表法随机分为5组,每组10只:(1)假手术组;(2)MI/RI组;(3)低剂量组(SBF 30 mg/kg);(4)中剂量组(SBF 75 mg/kg);(5)高剂量组(SBF 140 mg/kg)。采用冠状动脉前降支结扎法制备MI/RI模型。酶联免疫吸附试验测定血清中乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB)含量。NBT染色测定心肌梗死面积。Western blot测定p53、半胱氨酸天冬氨酸蛋白水解酶-3(Caspase-3)及B淋巴细胞瘤-2蛋白(Bcl-2)表达量。原位末端标记法(TUNEL)检测心肌细胞凋亡率。采用SPSS 25.0软件行统计分析。采用单因素方差分析进行组间比较。结果与MI/RI组比较,低、中、高组的LDH[(807.51±30.74)和(724.24±44.88)和(568.63±40.49)和(448.52±49.67)U/L]、CK-MB[(106.58±7.99)和(92.45±4.88)和(79.47±6.71)和(70.51±5.88)U/L]含量、p53[(1.19±0.05)和(1.06±0.03)和(1.02±0.03)和(0.77±0.03)]、Caspase-3[(1.50±0.05)和(1.01±0.05)和(0.96±0.04)和(0.41±0.04)]表达量、心肌梗死面积(37.21%和27.45%和16.08%和8.00%)、心肌细胞凋亡率(43.82%和35.91%和32.01%和22.67%)显著下降(P<0.01或P<0.05);Bcl-2[(1.02±0.04)和(1.37±0.08)和(1.42±0.04)和(1.62±0.04)]表达显著上升(P<0.01)。结论SBF预处理可抑制通过p53信号通路诱导的细胞凋亡途径,对缺血再灌注损伤的心肌起到保护作用。Objective To investigate the protective effect of Scutellaria barbata flavonoids(SBF)on myocardial ischemia/reperfusion injury(MI/RI)model and its underlying mechanism.Methods Fifty female SD rats randomly divided into 5 groups,with 10 rats in each group,that is,sham operation group(sham group),MI/RI group,and low-,middle-and high-dose SBF groups(30,75 and 140 mg/kg SBF respectively).The rat MI/RI models were established by ligating left anterior descending coronary arteries.Serum contents of creatine kinase isoenzyme-MB(CK-MB)and lactate dehydrogenase(LDH)were detected by enzyme linked immunosorbent assay(ELISA).The myocardial infarct area was measured using NBT staining.The protein levels of p53,Caspase-3,B-cell lymphoma-2(Bcl-2)were detected by Western blot.The apoptosis rate of cardiomyocytes was measured by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).SPSS statistics 25.0 software was used for statistical analysis.One-way ANOVA was employed for inter-group comparisons.Results Compared with the MI/RI group,the low-,middle-and high-dose groups had obviously decreased serum contents of LDH[(807.51±30.74)vs(724.24±44.88)vs(568.63±40.49)vs(448.52±49.67)U/L]and CK-MB[(106.58±7.99)vs(92.45±4.88)vs(79.47±6.71)vs(70.51±5.88)U/L],protein levels of p53[(1.19±0.05)vs(1.06±0.03)vs(1.02±0.03)vs(0.77±0.03)]and Caspase-3(1.50±0.05)vs(1.01±0.05)vs(0.96±0.04)vs(0.41±0.04)],area of myocardial infarct(37.21%vs 27.45%vs 16.08%vs 8.00%)and cardiomyocytes apoptosis rates(43.82%vs 35.91%vs 32.01%vs 22.67%)(P<0.01,P<0.05),but significantly increased expression levels of Bcl-2[(1.02±0.04)vs(1.37±0.08)vs(1.42±0.04)vs(1.62±0.04)](P<0.01).Conclusion SBF preconditioning can inhibit the apoptosis pathway induced by p53 signaling pathway,and play a protective effect against MI/RI.

关 键 词：心肌再灌注损伤 半枝莲总黄酮 P53 细胞凋亡 

分 类 号：R541.4[医药卫生—心血管疾病]