摘要
目的分析川芎嗪(TMP)对急性心肌梗死(AMI)大鼠心肌保护作用,并初步探讨其作用机制。方法将大鼠随机分为假手术组,模型组、川芎嗪低、中、高剂量组(120、240、360mg/kg)、阳性对照组(阿托伐他汀8mg/kg),每组15只。采用超声检测大鼠左心室功能;酶联免疫吸附法检测大鼠血清肿瘤坏死因子–α(TNF-α)、单核细胞趋化蛋白–1(MCP-1)水平;苏木素–伊红染色观察心肌组织病理损伤情况;Tunel染色检测大鼠心肌细胞凋亡率;实时荧光定量PCR法检测大鼠心肌组织miR-34a表达;免疫印迹法检测大鼠心肌组织中sirt1、p53、Bax、Bcl-2、cleaved-caspase3蛋白表达。结果与假手术组比较,模型组大鼠左心室舒张末期内径(LVEDD)、收缩末期内径(LVESD)升高,左室舒张期后壁厚度(LVPWDs)、左室射血分数(LVEF)、左室缩短分数(LVFS)降低;血清TNF-α、MCP-1水平升高,心肌细胞变性、坏死,伴有炎性细胞浸润;心肌组织病理学损伤评分、细胞凋亡率均升高;与模型组比较,各剂量川芎嗪组大鼠LVEDD、LVESD降低,LVPWDs、LVEF、LVFS升高,血清TNF-α、MCP-1水平降低,病理学损伤评分、心肌细胞凋亡率均降低。与假手术组比较,模型组大鼠心肌组织中miR-34a、p53蛋白表达[分别为(1.27±0.15)、(1.05±0.12)]升高,sirt1蛋白表达降低(0.37±0.06),Bax、cleaved-caspase3蛋白表达[分别为(1.54±0.19)、(1.12±0.14)]升高,Bcl-2蛋白表达降低(0.13±0.03)(P<0.05);与模型组比较,低、中、高剂量川芎嗪组大鼠心肌组织中miR-34a、p53蛋白表达[分别为(0.93±0.08)、(0.75±0.09)、(0.62±0.08)和(0.93±0.09)、(0.64±0.08)、(0.55±0.09)]降低,sirt1蛋白表达[分别为(0.46±0.05)、(0.55±0.07)、(0.68±0.09)]升高,Bax、cleaved-caspase3蛋白表达[分别为(1.17±0.16)、(0.78±0.06)、(0.47±0.04)和(0.89±0.11)、(0.73±0.09)、(0.42±0.10)]降低,Bcl-2蛋白表达[分别为(0.25±0.04)、(0.37±0.05)、(0.84±0.09)]升高(P<0.05)。结论川芎嗪对急性�
Objective To investigate protective effect and mechanism of tetramethylpyrazine (TMP) on myocardium in rats with acute myocardial infarction (AMI). Methods Totally 105 specific pathogen free Sprague-Dawley rats were assigned into a sham group, an model group (AMI), low, moderate, and high TMP dose groups (L-, M-, and H-TMP with intraperitoneal injection of TMP at doses of 120, 240, and 360 mg/kg 24 hours after the establishment of AMI model) and a positive control group (ACT with intraperitoneal injection of atorvastatin at the dose of 8 mg/kg). Left ventricular function was measured with ultrasonography;serum tumor necrosis factor (TNF-α) and monocyte chemotactic protein 1 (MCP-1) were detected with enzyme-linked immunosorbent assay (ELISA);hematoxylin-eosin (HE) staining was used to examine pathological changes of myocardial tissue in each group. Tunel staining was used to observe the apoptosis of myocardial cells;real-time fluorescence quantitative PCR (QRT-PCR) was used to detect the expression of microRNA-34a (miR-34a) in myocardium and expressions of sirtuin 1 (sirt1), p53, B-cellymphoma-2 (Bcl-2), Bcl-2associated X protein (Bax), and cleaved-caspase 3 in myocardium were detected with Western blot. Results Compared with the rats of sham group, the rats of AMI exhibited following significant abnormalities: increased left ventricular end diastolic dimension (LVEDD) and left ventricular end systolic dimension (LVESD) but decreased left ventricular posterior wall diameter at systole (LVPWDs), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS);declined serum TNF-α and MCP-1;deformation and necrosis of myocardial cells and inflammatory cell infiltration in myocardial tissues;higher score for myocardial histopathological damage and apoptotic rate;up-regulated expressions of miR-34a (1.27 ± 0.15 vs. 0.45 ± 0.16), p53 protein (1.05 ± 0.12 vs. 0.28 ± 0.04), Bax (1.54 ± 0.19 vs. 0.15 ± 0.04), and cleaved-caspase 3 protein (1.12 ± 0.14 vs. 0.14 ± 0.03) but down-regulat
作者
刘访遥
袁娜
王平
LIU Fang-yao;YUAN Na;WANG Ping(Cardiovascular Department,The Second Affiliated Hospital of University of South China,Hengyang,Hunan Province 421001,China)
出处
《中国公共卫生》
CAS
CSCD
北大核心
2019年第9期1229-1234,共6页
Chinese Journal of Public Health
基金
川芎嗪在内皮细胞抗炎反应中的作用(2016KJ30)
