心脑同治模型大鼠建立与表征参数研究

Establishment and Characterization Parameters of the Cardio-Cerebral Co-Treatment Model Rats

导出

摘要目的建立心脑同治大鼠模型,研究模型表征参数。方法SD大鼠采用丝线法制备缺血再灌注脑卒中模型,并采用冠状动脉前降支结扎法制备心肌缺血模型。实验设置假手术组[A组,等量0.5%羧甲基纤维素钠(CMC-Na)],模型对照组(B组,等量0.5%CMC-Na),银杏叶胶囊低、高剂量组(C_(1)组、C_(2)组,以总黄酮醇苷计6,12 mg/kg),各8只。心肌缺血30 min后,各组大鼠灌胃相应药物,连续14 d。表征参数研究包括心电图(ECG)-ⅡST段电压,心肌梗死、脑梗死面积比,心肌组织、脑组织形态,神经功能损伤严重程度评估量表(NSS)评分,心脏超声指标[M型心脏超声心动图、左室舒张末期容积(LVEDV)、左室收缩末期容积(LVESV)、射血分数(EF)],血流动力学指标[平均动脉压(MAP)、左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室压最大上升/下降速率(±dp/d_(tmax))],凝血因子指标[活化部分凝血活酶时间(APTT)和纤维蛋白原(Fib)],心肌酶与炎性因子[肌酸激酶MB型同工酶(CK-MB)、肿瘤坏死因子-α(TNF-α)]水平。采用双因素皮尔逊相关系数计算法评估EF和NSS评分(r_(1)),APTT与心肌梗死面积比(r_(2))、脑梗死面积比(r_(3)),Fib水平与心肌梗死面积比(r_(4))、脑梗死面积比(r_(5))的相关性。结果与B组比较,C_(1)组大鼠心肌组织的苍白色区域明显缩小,心脏室腔形态变化不明显,室间隔与左心室后壁运动幅度稍有增加;C_(2)组大鼠的苍白色区域进一步缩小,心脏室腔形态有所改善,收缩期室腔有所减小,室间隔与左心室后壁运动幅度大幅增加。与B组比较,C_(1)组、C_(2)组大鼠的ECG-ⅡST段电压分别降低21.72%(P>0.05)和37.30%(P<0.05);给药7 d后的NSS评分分别降低23.08%(P<0.05)和24.36%(P<0.01),给药14 d后的NSS评分分别降低18.31%(P<0.05)和32.39%(P<0.001);心肌梗死面积比分别降低16.00%(P<0.05)和20.11%(P<0.01),脑梗死面积比分别降低27.61%(P>0.05)和29.89%(P<0.05);给药14 d后的EF分别升高11.45%(P>0.05)和25.81%(P<0.01);LVEDP分别降低18.96%(P>0.05)和24.75%(P>0.05);Fib水平分别降低8.86%(P>0.05)和12.96%(P>0.05);TNF-α水平分别降低19.82%(P<0.05)和17.53%(P<0.05);LVEDV,LVESV,MAP,LVSP均无显著差异(P>0.05)。与B组比较,C_(2)组大鼠的APTT显著延长(P<0.05),+dp/d_(tmax)显著升高(P<0.05),CK-MB水平显著降低(P<0.05)。心脑功能相关性分析结果显示,r_(1),r_(2),r_(3),r_(4),r_(5)分别为-0.990,-0.987,-0.965,0.993,1.000。结论通过建立SD大鼠心脑同治模型,可同时体现出脑卒中、心肌缺血相关表征参数,且该心脑同治模型可用于心脑血管病的病理、生理过程研究及新药探索。 Objective To establish the cardio-cerebral co-treatment model rats,and to study the characterization parameters.Methods The ischemia-reperfusion stroke model was established by the silk thread method and the myocardial ischemia model was prepared by anterior descending coronary artery ligation.The experimental groups were divided into the sham group[group A,equal amount of 0.5%carboxymethyl cellulose sodium(CMC-Na)],the model control group(group B,equal amount of 0.5%CMC-Na),and low-and high-dose groups of Ginkgo Biloba Capsules(group C_(1)and group C_(2),the doses were 6 and 12 mg/kg calculated as total flavonol glycosides),with eight rats in each group.After 30 min of myocardial ischemia,rats in each group were orally administered with the corresponding drugs for 14 d.Characterization parameter studies included electrocardiography(ECG)-ⅡST segment voltage,myocardial infarction to cerebral infarction area ratio,myocardial and brain tissue morphology,Neurological Severity Scale(NSS)score,cardiac ultrasound indexes[M-mode echocardiography,left ventricular-end diastolic volume(LVEDV),left ventricular-end systolic volume(LVESV),ejection fraction(EF)],hemodynamic indexes[mean arterial pressure(MAP),left ventricular systolic pressure(LVSP),left ventricular-end diastolic pressure(LVEDP),maximum rate of left ventricular pressure rise/fall(±dp/d_(tmax))],coagulation factor indexes[activated-partial thromboplastin time(APTT)and fibrinogen(Fib)],the levels of myocardial enzymes and inflammatory factors[creatine kinase-MB isoenzyme(CK-MB),tumor necrosis factor-α(TNF-α)]were detected.The two-factor Pearson correlation coefficient calculation method was used to evaluate the correlation between EF and NSS scores(r_(1)),APTT and myocardial infarction area ratio(r_(2)),APTT and cerebral infarction area ratio(r_(3)),Fib level and myocardial infarction area ratio(r_(4)),and Fib level and cerebral infarction area ratio(r_(5)).Results Compared with those in group B,the pale areas of myocardial tissue of rats in group C_(1)significantly reduced,no significant change was observed in the shape of the heart chamber,and the interventricular septum and left ventricular posterior wall motion amplitude slightly increased;the pale area of rats in the C_(2)group further shrank,the shape of the cardiac chamber improved,the systolic chamber decreased,and the interventricular septum and left ventricular posterior wall motion amplitude significantly increased.Compared with those in group B,the ECG-ⅡST segment voltage of rats in groups C_(1)and C_(2)decreased by 21.72%(P>0.05)and 37.30%(P<0.05)respectively;the NSS scores of rats in groups C_(1)and C_(2)decreased by 23.08%(P<0.05)and 24.36%(P<0.01)respectively after 7 d of administration,the NSS scores of rats in groups C_(1)and C_(2)decreased by 18.31%(P<0.05)and 32.39%(P<0.001)respectively after 14 d of administration;the myocardial infarction area ratio of rats in groups C_(1)and C_(2)decreased by 16.00%(P<0.05)and 20.11%(P<0.01)respectively,and the cerebral infarction area ratio of rats in groups C_(1)and C_(2)decreased by 27.61%(P>0.05)and 29.89%(P<0.05)respectively;the EF of rats in groups C_(1)and C_(2)increased by 11.45%(P>0.05)and 25.81%(P<0.01)respectively after 14 d of administration;the LVEDP of rats in groups C_(1)and C_(2)decreased by 18.96%(P>0.05)and 24.75%(P>0.05)respectively;the Fib level of rats in groups C_(1)and C_(2)decreased by 8.86%(P>0.05)and 12.96%(P>0.05)respectively;the TNF-αlevel of rats in groups C_(1)and C_(2)decreased by 19.82%(P<0.05)and 17.53%(P<0.05)respectively;but the LVEDV,LVESV,MAP,LVSP in the groups C_(1)and C_(2)had no significant difference.Compared with those in group B,the APTT in group C_(2)significantly prolonged(P<0.05),the+dp/d_(tmax)of rats in group C_(2)significantly increased(P<0.05),and the CK-MB level in group C_(2)significantly decreased(P<0.05).The correlation analysis of cardiovascular and cerebrovascular functions showed that the r_(1),r_(2),r_(3),r_(4),and r_(5)were-0.990,-0.987,-0.965,-0.993,and 1.000,respectively.Conclusion By establishing the cardio-cerebral co-treatment model rats,it is possible to simultaneously reflect the characteristic parameters related to stroke and myocardial ischemia,and the cardio-cerebral co-treatment model can be used for the study of the pathological and physiological processes of cardiovascular and cerebrovascular diseases,and the exploration of new drugs.

作者王诗元郝春华刘杰张津溢王维亭 WANG Shiyuan;HAO Chunhua;LIU Jie;ZHANG Jinyi;WANG Weiting(School of Nursing,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Winhonour Medtech Co.,Ltd.,Tianjin 300192,China)

机构地区天津中医药大学护理学院天津维佳医药科技有限公司

出处《中国药业》 2026年第1期67-73,共7页 China Pharmaceuticals

基金天津市科学技术局天开高教科创园企业研发专项项目[23YFZXYC00002]。

关键词心脑同治脑卒中心肌梗死动物模型银杏叶胶囊 SD大鼠表征参数 cardio-cerebral co-treatment stroke myocardial infarction animal model Ginkgo Biloba Capsules SD rats characterization parameters