【作者】 赵彦青；

【导师】 孙塑伦； 高颖；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2006， 博士

【摘要】 脑出血患者常发生继发性的心肌损害,临床上称为脑心综合征,表现为心电图改变、心律失常乃至心跳停止,常加速病情恶化,影响预后。脑心综合征的研究临床报道很多,而实验研究却很少,其机制尚不清楚,亟待我们去研究和探讨。临床上心脑血管疾病之间相互联系和相互影响,这已为很多临床医生所关注。本课题研究脑出血诱发心肌损伤的机制,同时也对心脑相关的理论作初步的探讨。目的:探讨脑出血诱发心肌损伤的病理生理机制,观察扶正护脑胶囊对心肌的保护作用,并初步探讨心脑相关的理论。方法:选用胶原酶加肝素联合注射建立大鼠脑出血诱发心肌损伤模型。设假手术组、模型组、扶正护脑组和安宫牛黄组。给药方法均为每日灌胃,实验各组分别在造模后6h、24h、72h三个时相点取材,观察各项指标。①分别采用生化方法和双抗夹心ELISA方法检测血清CK-MB和cTnI的含量,证明大鼠脑出血急性期存在心肌损伤,并观察扶正护脑胶囊的抗心肌损伤作用;②通过HE染色观察脑血肿的形成情况,通过HE染色、碱性复红苦味酸染色、透射电镜等观察脑出血大鼠心肌形态学的改变以及扶正护脑胶囊的防治效应;③采用高效液相-电化学法测定大鼠蓝斑和心肌组织NE的含量,并与血清CK-MB、cTnI含量作相关性分析,探讨蓝斑-去甲肾上腺素系统(LC-NE)在脑出血诱发心肌损伤中的作用及扶正护脑胶囊的干预效果;④采用放免方法测定大鼠心肌组织ET、TXB2、6-Keto-PGF1α的含量,采用硝酸还原酶法测定大鼠心肌组织NO含量,并与血清CK-MB、cTnI含量作相关性分析,探讨ET/NO、TXB2/6-Keto-PGF1α平衡紊乱在脑出血诱发心肌损伤中的作用以及扶正护脑胶囊的干预效果;⑤采用硫代巴比妥酸法(TBA法)测定心肌组织MDA含量,采用黄嘌呤氧化酶法测定心肌组织SOD活性,并与血清CK-MB、cTnI含量作相关性分析,探讨氧化应激在脑出血诱发心肌损伤中的作用以及扶正护脑胶囊的干预效果;⑥采用免疫组织化学SABC法,测定心肌组织TNF-α、IL-1β和HSP70的蛋白表达,并进行图像分析,观察所测指标的IOD值。并与血清CK-MB、cTnI含量作相关性分析,探讨炎性反应在脑出血诱发心肌损伤中的作用以及机体内源性的自我保护机制。结果:1血清CK-MB和cTnI的含量测定模型组各时间点大鼠血清CK-MB和cTnI较同期假手术组显著升高(P<0.01),术后24h达到高峰,CK-MB在术后72h下降显著,cTnI在术后72h稍有下降。扶正护脑组、安宫牛黄组CK-MB和cTnI含量较同期模型组显著下降(P<0.05,P<0.01)。2脑和心肌组织的病理形态学特征更多还原

【Abstract】 Intracerebral hemorrhage patients always have myocardial damages secondary, we call this cerebrocardiac syndrome(CCS).The syndrome was manifested as abnormal electro- cardiogram, arrhythmia, even stopping heartbeat suddenly.It accelerates the pathogenetic condition, affect the patient’s prognosis, and make the treatment more difficult.The clinical proof of CCS always is more,but experimentmal study is less,and its mechanism is still dimness.The relationship is very close between cardiovascular disease and cerebrovascular disease. This research will discuss the mechanism of CCS and the simple theory about the correlation of heart and brain. ObjectiveDiscuss the mechanism of CCS and the simple theory about the correlation of heart and brain,at the same time observe the effect of Fuzhenghunao capsule. MethodThe cerebral hemorrhage model was established by infusing collagenase and heparin into rat caudate. Male rats are divided randomly into four groups: Sham group; Model group; Fuzhenghunao capsule group(Fzhn);Angongniuhuang pill group(Agnh); Rats were taken orally , and all of the experimental indicators were detected at 6h,24h and 72h.1. The content of CK-MB and cTnI in serum were measured with biochemical methods and enzyme-linked immunosorbent assay(ELISA) respectively,and observe the protection effects of Fzhn capsule.2. Observed the myocardial histo-morphology changes of rats and the protection effects of Fzhn by methods of HE staining, HBFP staining, transmission electron microscope(TEM).3. The content of NE in the myocardial tissues and locus ceruleus tissues were detected by the high performance liquid phase-electrochemical method(HPLC),and explore the correction between NE content and CK-MB conten,cTnI content.Study the effect of locus ceruleus noradrenalin system(LC-NE) on the myocardial damage.4. The content of ET,TXB2 and 6-Keto-PGF1αin the myocardial tissues were tested by radioimmunoassay and NO content was done by nitrate reductase method. Explore the correction between the content of ET,NO,TXB2 , 6-Keto-PGF1αand the content of CK-MB and cTnI.Discuss the effect of their disorderly condition on the myocardial damage.5. Superoxide dismutase(SOD) activity and maleic dialdehyde (MDA) content in the myocardial tissues were tested by actinochemistry method. Explore the correction between SOD activity, MDA content and the content of CK-MB and cTnI,and then Study the effect of oxidative stress on the myocardial damage.更多还原