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双参通脉颗粒抑制ERK1/2-NF-κB信号通路改善急性心肌梗死模型大鼠心肌损伤作用机制研究

Mechanism of Shuangshen Tongmai Granules Improving Myocardial Injury in Model Rats with Acute Myocardial Infarction by Inhibiting ERK1/2-NF-κB Signaling Pathway

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【作者】 吴杨王秀詹三华高杉

【Author】 WU Yang;WANG Xiu;ZHAN Sanhua;GAO Shan;People’s Hospital of Tongling City;School of Pharmacy,Anhui Medical University;

【机构】 安徽省铜陵市人民医院安徽医科大学药学院

【摘要】 目的 探讨双参通脉颗粒(GSG)是否通过抑制细胞外活化蛋白激酶1/2-核因子-κB(ERK1/2-NF-κB)信号通路改善急性心肌梗死(AMI)模型大鼠的心肌损伤。方法 将60只SD大鼠分为假手术组(A组,等量生理盐水),模型组(B组,等量生理盐水),阿托伐他汀组(C组,8 mg/kg),GSG低、中、高剂量组(D1组、D2组、D3组,5,10,15 g/kg),各10只。除A组外,其余各组大鼠通过左冠状动脉前降支结扎建造AMI模型,造模成功后24 h灌胃相应药物。检测各组大鼠的心功能;采用酶联免疫吸附试验(ELISA)法检测血清炎性因子,按试剂盒操作检测生化指标;分别采用2,3,5-氯化三苯基四氮唑(TTC)染色法、苏木精-伊红(HE)染色法、原位末端标记(TUNEL)法检测心肌梗死、病理损伤及细胞凋亡情况;采用免疫印迹(Western blot)法检测细胞凋亡与通路相关蛋白表达情况。结果 与B组比较,D1组、D2组、D3组大鼠左心室收缩压(LVSP)、平均动脉压(MAP)、左心室内压上升最大速率(+dp/dtmax)、B细胞淋巴瘤-2(Bcl-2)表达水平均显著升高(P<0.05),左心室内压下降最大速率(-dp/dtmax)、左心室舒张末压(LVEDP)、肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白1(MCP-1)、白细胞介素(IL)-6、IL-1β、肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)、心肌梗死程度、心肌细胞凋亡率、胱天蛋白酶-3(caspase-3)、B淋巴细胞瘤2相关X蛋白(Bax)、p-ERK1、p-ERK2、NF-κB p65表达水平均显著降低(P<0.05)。结论 GSG可能通过抑制ERK1/2-NF-κB信号通路改善AMI模型大鼠的心肌损伤。

【Abstract】 Objective To investigate whether Shuangshen Tongmai Granules can improve myocardial injury in acute myocardial infarction (AMI) model rats by inhibiting the extracellular signal-regulated kinases 1/2-nuclear factor-κB (ERK1/2-NF-κB) signaling pathway.Methods A total of 60 SD rats were divided into the sham operation group (group A,equal volume of phgsiological saline),model group (group B,equal volume of phgsiological saline),atorvastatin group (group C,8 mg/kg),and low-,medium-,and high-dose Shuangshen Tongmai Granules groups (groups D1,D2,D3,5,10,15 g/kg),with 10 rats in each group.Except for rats in group A,rats in the other groups were used to establish AMI models by ligating the left anterior descending coronary artery.At 24 h after successful modeling,corresponding drugs were administered by gavage.The cardiac function of rats in each group was detected.The serum inflammatory factors were detected by the enzyme-linked immunosorbent assay (ELISA),and biochemical indicators were detected according to the test kits.Myocardial infarction,pathological damage,and cell apoptosis were detected by the TTC staining method,hematoxylin eosin (HE) staining method,and TdT-mediated dUTP nick end labeling (TUNEL) method,respectively.The expression of apoptosis-related protiens and pathway-related proteins in cells was detected by the Western blot.Results Compared with those in group B,the left ventricular systolic pressure (LVSP),mean arterial pressure (MAP),maximal left ventricular pressure rising rate (+dp/dtmax),and expression levels of B-cell lymphoma 2 (Bcl-2) significantly increased in groups D1,D2,and D3,while the maximal left ventricular pressure decreasing rate(-dp/dtmax),left ventricular end-diastolic pressure (LVEDP),tumor necrosis factor-α (TNF-α),monocyte chemoattractant protein-1 (MCP-1),interleukin (IL)-6,IL-1β,cardiac troponin I (cTnI),creatine kinase-MB (CK-MB),degree of myocardial infarction,myocardial cell apoptosis rate,the expression levels of caspase-3,BCL2-associated X protein (Bax),p-ERK1,p-ERK2,and NF-κB p65 significantly decreased in groups D1,D2,and D3(P<0.05).Conclusion Shuangshen Tongmai Granules may improve myocardial injury in rats with myocardial infarction by inhibiting ERK1/2-NF-κB signaling pathway.

【基金】 安徽省高校自然科学研究项目[KL2020A0860]
  • 【文献出处】 中国药业 ,China Pharmaceuticals , 编辑部邮箱 ,2025年03期
  • 【分类号】R285.5
  • 【下载频次】83
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