通塞脉片对急性心肌梗死大鼠的治疗效果及机制研究  

Therapeutic effect and mechanism of Tongsaimai tablet on rats with acute myocardial infarction

作　　者：郭怀蕾 谭刚[2] 杨秀云[2] 邢人鑫[1] Guo Huailei;Tan Gang;Yang Xiuyun;Xing Renxin(Department of Pharmacy,Sichuan Academy of Medical Sciences·Sichuan Provincial People's Hospital,Chengdu 610072,Sichuan Province,China)

机构地区：[1]四川省医学科学院、四川省人民医院药学部,成都610072 [2]四川省医学科学院、四川省人民医院心血管内科,成都610072

出　　处：《中华老年心脑血管病杂志》2024年第7期817-823,共7页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：四川省卫生健康委员会科研课题项目(22PJ135)。

摘　　要：目的 探究通塞脉片对急性心肌梗死(AMI)大鼠心功能、心肌损伤、炎症及纤维化的影响及可能的作用机制。方法 选取大鼠73只,以手术结扎冠状动脉左前降支的方式建立AMI大鼠模型,成功造模的AMI大鼠60只随机分为模型组、p38丝裂原活化蛋白激酶(MAPK)抑制剂组(MAPK抑制剂10 mg/kg)、通塞脉片低剂量组(通塞脉片0.28 g/kg)、通塞脉片高剂量组(通塞脉片0.56 g/kg)、通塞脉片高剂量+p38 MAPK抑制剂组(通塞脉片0.56 g/kg+MAPK抑制剂10 mg/kg),每组12只;另取12只正常大鼠同造模方法进行相同的手术操作但不结扎冠状动脉左前降支作为假手术组。各组给予相应干预14 d,超声影像系统检测心功能指标[左心室舒张末期容积(LVEDV)、左心室收缩末期容积(LVESV)、左心室射血分数(LVEF),左心室短轴缩短率(LVFS)];酶联免疫吸附法检测心肌损伤指标[心肌肌钙蛋白I(cTnI)、乳酸脱氢酶(LDH)]和炎性因子[肿瘤坏死因子α(TNF-α)、白细胞介素(IL)6、IL-10]水平;苏木精-伊红染色、Masson染色观察心肌病理变化和纤维化程度;免疫组织化学染色检测心肌胶原组织Ⅰ型(CollagenⅠ)和心肌胶原组织Ⅲ型(CollagenⅢ)表达;Western blot检测心肌组织p38 MAPK/基质金属蛋白酶9(MMP-9)通路相关蛋白表达。结果 与模型组比较,p38 MAPK抑制剂组、通塞脉片低剂量组、通塞脉片高剂量组心肌组织病理损伤有不同程度的缓解,LVEDV、LVESV、cTnI、LDH、TNF-α、IL-6、心肌胶原容积分数(CVF)、CollagenⅠ、CollagenⅢ、磷酸化p38 MAPK(p-p38 MAPK)/p38 MAPK和MMP-9蛋白表达显著降低,LVEF、LVFS、IL-10显著升高(P<0.05)。与p38 MAPK抑制剂组和通塞脉片高剂量组比较,通塞脉片高剂量+p38 MAPK抑制剂组LVEDV、LVESV、cTnI、LDH、TNF-α、IL-6、CVF、CollagenⅠ、CollagenⅢ、p-p38 MAPK/p38 MAPK和MMP-9蛋白表达显著降低,LVEF[(64.31±7.78)%vs(52.89±7.05)%、(57.40±7.42)%]、LVFS[(34.51±5.29)%vs(27.02±5.01)、(25.04Objective To determine the effects of Tongsaimai tablet on cardiac function,myocardial injury,inflammation and fibrosis in rats with acute myocardial infarction(AMI)and investigate possible mechanism.Methods A total of 73rats were subjected to establish rat model of AMI by ligation of the left anterior descending coronary artery.The 60successfully modeled AMI rats were randomly divided into model group,p38mitogen-activated protein kinase(MAPK)inhibitor group(10mg/kg),low-and high-dose Tongsaimai tablet groups(0.28and 0.56g/kg),and highdose Tongsaimai tablet+p38MAPK inhibitor group(as above doses),with 12rats in each group.Another 12normal rats served as the sham operation group.After corresponding intervention for 14d,echocardiography was applied to evaluate the heart function,including left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left ventricular ejection fraction(LVEF),and left ventricular short axis shortening rate(LVFS).The levels of myocardial injury indexes[cardiac troponin I(cTnI),lactate dehydrogenase(LDH)]and inflammatoryfactors(TNF-α,IL-6,IL-10)were detected by ELISA.HE and Masson staining were used to observe pathological changes and fibrosis in myocardial tissues.The expression of CollagenⅠandCollagen Ⅲ in myocardial tissue was detected by immunohistochemical staining.The proteinexpression of p38MAPK/matrix metalloproteinase(MMP)-9pathway related proteins in myocardial tissues was detected by Western blotting.Results Compared with model group,the conditions were alleviated in the p38MAPK inhibitor group,and low-and high-dose Tongsaimai tabletgroups,with milder pathological damage in myocardial tissue,obviously decreased LVEDV,LVESV,cTnI,LDH,TNF-αand IL-6levels,CVF,expression of CollagenⅠ,CollagenⅢ,p-p38MAPK/p38MAPK and MMP-9,and increased LVEF,LVFS and IL-10level(P <0.05).Compared with p38MAPK inhibitor group and high-dose Tongsaimai tablet group,high-dose Tongsaimai tablet+p38MAPK inhibitor group had LVEDV,LVESV,cTnI,LDH,TNF-α,IL-6,CVF and Collag

关 键 词：通塞脉片 心肌梗死 心室功能 心房功能 心肌损伤 

分 类 号：R285.5[医药卫生—中药学]