连翘酯苷A对大鼠急性心肌缺血保护作用及机制研究

作者	单位
王琛，赵小建，孟哲，李海禹，桑海强	1.郑州大学第一附属医院心血管内科（郑州 450052）；2.河南省人民医院心血管内科（郑州 463599）

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中文摘要:

目的观察连翘酯苷A（FA）对大鼠急性心肌缺血损伤的影响并探讨其作用机制。方法将SD大鼠随机分为假手术（n=25）、模型（n=17）、FA低剂量（n=19）、FA高剂量组（n=20）。除假手术组外，利用大鼠冠状动脉前降支结扎的方法构建急性心肌缺血模型。FA低、高剂量组于造模前1天分别给予FA 20、40 mg/（kg·d）灌胃，假手术组和模型组给与等量生理盐水灌胃，连续7天。采用HE染色观察心肌组织病理学改变，ELISA检测大鼠血清中丙二醛（MDA）、超氧化物歧化酶（SOD）、白介素-6（IL-6）、IL-1β、肿瘤坏死因子-α（TNF-α）水平，Western Blot观察心肌Toll 样受体4（TLR4）、髓样分化因子（MyD88）、磷酸化核因子κB （p-NF-κB） p65蛋白表达，免疫组化法观察心肌p-NF-κB p65蛋白表达。结果假手术组大鼠心肌细胞排列较为整齐，模型组大鼠的心肌纤维排列紊乱，横纹模糊，可见细胞肿胀，伴有大量炎性细胞浸润，FA低、高剂量组有所改善。与假手术组比较，模型组大鼠血清中SOD水平降低（P<0.01），血清MDA、IL-1β、IL-6、TNF-α水平、心脏组织TLR4、MyD88、p-NF-κBp65的蛋白表达升高（P<0.01）。与模型组比较，FA组SOD水平升高（P<0.01），IL-1β、IL-6、TNF-α、MDA水平、心脏TLR4、MyD88、p-NF-κB p65蛋白表达降低（P<0.01）。FA高、低剂量组各指标比较，差异无统计学意义（P>0.05）。结论 FA可通过抑制TLR4/NF-κB信号通路的激活来发挥改善大鼠急性心肌缺血的作用。

英文摘要:

Objective To observe the effect and mechanism of forsythiaside A （FA） for acute myocardial ischemia injury rats. Methods SD rats were randomly divided into sham operation group（n=25），group model（n=17），low-dose FA group（n=19） and high-dose FA dose group（n=20）. Acute myocardial ischemia model was established by ligation of anterior descending coronary artery in rats except sham operation group. Low-dose and high-dose FA groups were given 20 and 40 mg·kg-1·d-1 FA by gavage 1 day before modeling，respectively，while sham operation group and model group were given equal volume of normal saline gavage，the course was 7 consecutive days. HE staining was used to observe the myocardial tissue pathology change. The rat serum malondialdehyde （MDA），superoxide dismutase （SOD），interleukin（IL）-6，IL-1β，tumor necrosis factor alpha（TNF-α） levels were detected by ELISA. The protein expressions of myocardial toll-like receptor 4（TLR4） and myeloid differentiation factor（MyD88），phosphorylation nuclear factor-κB （p-NF-κB） p65 were detected by Western Blot. And immunohistochemmistry was used to detected the myocardial p-NF-κB p65 protein expression. Results The arrangement of myocardial cells in sham operation group was more orderly. The arrangement of myocardial fibers in the model group was disordered，the transverse lines were blurred，the cells were swollen，and a large number of inflammatory cells were infiltrated. The improvement was found in FA groups. Compared with sham operation group， the serum SOD decreased（P<0.01），serum MDA，IL-1β，IL-6，TNF-α，the protein expressions of TLR4，MyD88，p-NF-κB p65 in heart tissues increased in model group（P<0.01）. Compared with model group，the serum SOD increased（P<0.01），serum IL-1β，IL-6，TNF-α，the protein expression of TLR4，MyD88，p-NF-κB p65 in heart tissues decreased in FA groups（P<0.01）. There was no statistical difference between high-dose FA group and low-dose FA group（P>0.05）. Conclusion FA can improve acute myocardial ischemia in rats by inhibiting the activation of TLR4/NF-κB signaling pathway.

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