青蒿素对大鼠心肌缺血再灌注损伤的影响及其作用机制探讨

摘要

目的：探讨青蒿素对大鼠心肌缺血再灌注损伤的影响及其可能作用机制。方法采用大鼠心肌缺血再灌注模型(缺血30 min，再灌注4 h)，雄性SD大鼠30只根据随机数字表随机分为三组：假手术组(SO组，n=10)、缺血再灌注组(I/R组，n=10)和青蒿素治疗组(A+I/R组，n=10，Artemisinin：25 mg/kg，Tid，造模前1 d灌胃)。检测心肌损伤标记物肌酸激酶(CK)、乳酸脱氢酶(LDH)和肌钙蛋白I (cTnI)；检测炎症因子高迁移率族蛋白1(HMGB1)、白介素17A (IL-17A)、肿瘤坏死因子α(TNF-α)、干扰素γ(INF-γ)和白介素6(IL-6)；检测总p38(t-p38)和磷酸化p38(p-p38)。结果与SO组比较，I/R组中心肌损伤标记物CK [(3891±245.44) U/L vs (1539±140.57) U/L]、LDH [(1917±140.54) U/L vs (889±87.23) U/L]、cTnI [(66.34±2.13) pg/mL vs (26.45±1.72) pg/mL]；炎症因子HMGB1[(0.423±0.059) vs (0.301±0.067)]、IL-17A [(149.29±5.88) pg/mL vs (55.26±4.33) pg/mL]、TNF-α[(185.27±5.61) pg/mL vs (95.34±3.56) pg/mL]、INF-γ[(418.86±12.37) pg/mL vs (223.35±10.51) pg/mL]、IL-6[(156.89±6.01) pg/mL vs (65.43±4.21 pg/mL]、p-p38[(0.416±0.025) vs (0.188±0.013)]表达明显增加，差异均有统计学意义(P<0.05)；与I/R比较，A+I/R组中心肌损伤标记物CK [(1934±199.56) U/L]、LDH [(973±79.47) U/L]、cTnI [(38.1±2.69) pg/mL]和炎症因子HMGB1(0.174±0.026)、IL-17A [(93.65±2.69) pg/mL]、TNF-α[(145.85±3.92) pg/mL]、INF-γ[326.54±9.81] pg/mL]、IL-6[(95.47±3.16) pg/mL]、p-p38[(0.297±0.021)]表达明显降低，差异均有统计学意义(P<0.05)。结论青蒿素可能通过抑制p38MAPK通路减轻I/R中炎症反应；青蒿素亦可通过抑制炎症反应减轻心肌缺血再灌注损伤。%Objective To investigate the effects and possible mechanism of artemisinin on myocardial isch-emia reperfusion injury in rats. Methods Rat I/R models were established by ischemia 30 min and reperfusion 4 h. Thirty SD rats were divided into three groups according to the random number table:sham operation group (SO, n=10), ischemia and reperfusion group (I/R, n=10) and artemisinin treatment group (A+I/R, n=10). Cardiac injury markers, in-cluding creatine kinase (CK), lactate dehydrogenase (LDH), and cardiac troponin (cTnI) were detected. The inflammato-ry cytokines [high mobility group box protein 1 (HMGB1), interleukin-17A (IL-17A), tumor necrosis factor-α(TNF-α), gamma interferon (INF-γ), interleukin-6 (IL-6)], total p38 (t-p38), phosphorylation p38 (p-p38)) were detected. Results Compared with SO group, I/R group was significantly higher (P<0.05) in the cardiac injury markers of CK [(3 891±245.44) U/L vs (1 539±140.57) U/L], LDH [(1 917±140.54) U/L vs (889±87.23) U/L] and cTnI [(66.34±2.13) pg/mL vs (26.45 ± 1.72) pg/mL], the inflammatory cytokines of HMGB1 [(0.423 ± 0.059) vs (0.301 ± 0.067)], IL-17A [(149.29 ± 5.88) pg/mL vs (55.26±4.33) pg/mL], TNF-α[(185.27±5.61) pg/mL vs (95.34±3.56) pg/mL], INF-γ[(418.86±12.37) pg/mL vs (223.35 ± 10.51) pg/mL], IL-6 [(156.89 ± 6.01) pg/mL vs (65.43 ± 4.21) pg/mL], and p-p38 [(0.416 ± 0.025) vs (0.188 ± 0.013)]. Compared with I/R group, A+I/R group was significantly lower (P<0.05) in the cardiac injury markers of CK [(1 934 ± 199.56) U/L], LDH [(973 ± 79.47) U/L] and cTnI [(38.1 ± 2.69) pg/mL], inflammatory cytokines of HMGB1 [(0.174 ± 0.026)], IL-17A [(93.65 ± 2.69) pg/mL], TNF-α[(145.85 ± 3.92) pg/mL], INF-γ[(326.54 ± 9.81) pg/mL], IL-6 [(95.47±3.16) pg/mL], and p-p38 [(0.297±0.021)]. Conclusion Artemisinin can inhibit inflammatory responses proba-bly via suppressing p38 MAPK signaling pathway activation, and thus attenuate myocardial I/R injury.