| 张伟奇,周硕,李铁成.匹立尼酸基于TLR4/NF-κB信号通路对大鼠心肌缺血再灌注损伤的作用[J].中华老年多器官疾病杂志,2022,21(8):602~607 |
| 匹立尼酸基于TLR4/NF-κB信号通路对大鼠心肌缺血再灌注损伤的作用 |
| Pirinixic acid protects rats against myocardial ischemia-reperfusion injury based on TLR4/NF-κB signaling pathway |
| 投稿时间：2022-01-04 |
| DOI：10.11915/j.issn.1671-5403.2022.08.129 |
| 中文关键词: 心肌缺血再灌注损伤 匹立尼酸 核因子-kB信号通路 炎症反应 |
| 英文关键词:myocardial ischemia-reperfusion injury pirinicix acid nuclear factor-κB signaling pathway inflammatory reaction This work was supported by the Natural Science Foundation of Liaoning Province |
| 基金项目:辽宁省自然科学基金(20170540372) |
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| 中文摘要: |
| 目的 探讨匹立尼酸(Wy-14643)对大鼠心肌缺血/再灌注损伤(MI/RI)的防治作用及机制。方法 将40只大鼠随机分为5组,每组8只:(1)假手术组(Sham组)；(2)缺血再灌注组(MI/RI组)；(3)匹立尼酸低剂量组(W1组,1mg/kg)；(4)匹立尼酸中剂量组(W2组,4mg/kg)；(5)匹立尼酸高剂量组(W3组,8mg/kg)。采取冠状动脉前降支结扎再灌注的方式建立MI/RI模型。酶联免疫吸附法测定血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、白细胞介素-6(IL-6)及肿瘤坏死因子-α(TNF-α),测定心肌梗死面积,光镜观察心肌组织病理改变。检测心肌组织TOLL样受体-4(TLR4)及核因子-κBp65蛋白的表达。采用SPSS 23.0软件进行数据分析。采用单因素方差分析和Bonferroni检验进行组间比较。结果 与MI/RI组比较,W1组、W2组、W3组血清CK-MB[(94.81±8.41)、(82.41±7.20)、(69.40±6.52)和(119.91±12.71)U/L]、LDH[(750.73±86.44)、(654.94±79.25)、(565.26±86.00)和(911.48±87.15)U/L]、IL-6[(176.75±11.89)、(162.67±8.18)、(146.13±10.48)和(194.93±13.91)pg/ml]、TNF-α[(80.67±7.38)、(69.67±5.15)、(51.22±7.00)和(90.44±6.68)pg/ml]含量、心肌梗死面积(28.00%、16.93%、8.38%和35.88%)均显著降低(P<0.05),TLR4[(1.00±0.03)、(0.92±0.03)、(0.69±0.04)和(1.33±0.03)]、核因子-κBp65[(1.01±0.03)、(0.94±0.03)、(0.72±0.04)和(1.12±0.04)]的表达下调(P<0.05)。结论 匹立尼酸预处理可抑制通过核因子-κB信号通路介导的炎症反应来保护MI/RI的心肌。 |
| 英文摘要: |
| Objective To investigate the protective effect of pirinixic acid (Wy-14643) on myocardial ischemia/reperfusion injury (MI/RI) in rats and its underlying mechanism. Methods Forty rats were randomly divided into 5 groups, with 8 rats in each group:sham operation group (sham group), ischemia-reperfusion group (MI/RI group), and low-, middle- and high-dose pirinixic acid groups (W1, W2, W3 groups, at a concentration of 1,4 and 8 mg/kg, respectively). MI/RI model was established by ligation and reperfusion of anterior descending coronary artery. Serum creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Myocardial infarction area was measured and pathological changes of myocardial tissue were observed under a light microscope. The protein expression of toll-like receptor 4(TLR4) and nuclear factor-κBp65 in myocardium was detected with Western blotting. SPSS statistics 23.0 was used for statistical analysis. Data comparison between two groups was perfomed using ANOVA analysis and Bonferroni test depending on data type. Results Serum contents of CK-MB [(94.81±8.41), (82.41±7.20) and (69.40±6.52) vs (119.91±12.71) U/L], LDH [(750.73±86.44), (654.94±79.25) and (565.26±86.00) vs (911.48±87.15) U/L], IL-6 [(176.75±11.89), (162.67±8.18) and (146.13±10.48) vs (194.93±13.91) pg/ml] and TNF-α [(80.67±7.38), (69.67±5.15) and (51.22±7.00) vs (90.44±6.68) pg/ml] were significantly lower, the area of myocardial infarction (28.00%, 16.93% and 8.38% vs 35.88%) was obviously smaller, and the expression levels of TLR4 [(1.00±0.03), (0.92±0.03) and (0.69±0.04) vs (1.33±0.03)] and nuclear factor-κBp65 [(1.01±0.03), (0.94±0.03) and (0.72±0.04) vs (1.12±0.04)] were down-regulated in the W1, W2, W3 groups when compared with the MI/RI group (P<0.05). Conclusion Preconditioning with pirinixic acid protects MI/RI myocardium by inhibiting inflammation mediated by the nuclear factor-κB signaling pathway. |
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