重组人促红细胞生成素预处理在风湿性心脏瓣膜病围手术期心肌保护作用的研究
发布时间：2018-07-16 15:56
【摘要】：目的:心肌保护一直是体外循环(Cardiopulmonary Bypass,CPB)心脏直视手术研究的热点。术后心功能障碍与原发疾病、CPB时心肌缺血、缺血-再灌注损伤、手术创伤等因素有关,缺血-再灌注损伤是心肌损伤的一个重要因素。有研究报道重组人促红细胞生成素(Recombinant human erythropoietin,r Hu EPO)在心肌缺血-再灌注损伤中具有保护作用,但对其在CPB心脏直视手术围手术期心肌保护作用研究较少。因此,本课题通过观察r Hu EPO预处理对风湿性心脏瓣膜病围术期心肌肌钙蛋白I(cardiac troponin I,c Tn I)、磷酸肌酸激酶同工酶(creatine kinase-MB,CK-MB)、心肌细胞超微结构改变的影响,探讨r Hu EPO预处理的心肌保护作用。方法:选择风湿性心脏瓣膜病人(拟行二尖瓣+主动脉瓣双瓣瓣膜置换)40例,年龄40~60岁,术前心功能II或III级(NYHA),术前无肝肾功能障碍、甲状腺疾病、糖尿病等代谢障碍性疾病;无心绞痛、心肌梗死、高血压等病史;无长期使用糖皮质激素和严重感染性疾病。采用随机数字表分为1个对照组(A组),3个实验组(B、C、D组),每组10例。所有患者均在静吸复合麻醉、中度低温和血液中度稀释下进行手术。实验组术前三天每天皮下注射r Hu EPO,B组r Hu EPO每次注射剂量为50u/Kg,C组为100u/Kg,D组为200u/Kg,对照组(A组)未作特殊处理。所有患者均在麻醉诱导前(T0)、主动脉开放时(T1)、主动脉开放后2h(T2)、主动脉开放后6h(T3)、主动脉开放后12h(T4)、主动脉开放后24h(T5)、主动脉开放后36h(T6)、主动脉开放后72h(T7)、主动脉开放后96h(T8)、主动脉开放后120h(T9)十个时间点采取静脉血标本,分别检测血常规、血清c Tn I、血清CK-MB的浓度变化;分别于阻断主动脉时、阻断主动脉后30min和阻断主动脉后60min三个时间点切取三小块右心房梳状肌组织。结果:所有患者围手术期无并发症发生,均痊愈出院。四组患者CPB心脏瓣膜置换术前和术中的一般资料比较差异均无统计学意义(P0.05)。三个不同剂量r Hu EPO预处理的实验组和对照组患者血清c Tn I、血清CK-MB浓度在麻醉诱导前均处于正常范围内,主动脉阻断后开始增高,主动脉开放后2h明显增高,主动脉开放后12h达到最高值,随后逐渐下降,分别在术后120h、72h接近正常值。组内各时间点血清c Tn I、血清CK-MB浓度均较麻醉诱导前升高,差异具有统计学意义(P0.05)。而同一时间点三个不同剂量r Hu EPO预处理的实验组与对照组进行两两组间比较:不同剂量r Hu EPO预处理组在各时间点血清c Tn I、血清CK-MB浓度明显低于对照组(P0.05),且血清c Tn I、血清CK-MB浓度随r Hu EPO预处理剂量的增大而降低,差异具有统计学意义(P0.05)。三个不同剂量r Hu EPO预处理的实验组和对照组患者右心房梳状肌组织的变化,随着阻断时间的延长心肌细胞肌丝、肌节、线粒体、肌浆网等超微结构损伤程度越重,且心肌细胞肌丝、肌节、线粒体、肌浆网等超微结构损伤程度随着r Hu EPO预处理剂量的增大而减轻。结论：1.血清c Tn I、血清CK-MB浓度在麻醉诱导前均处于正常范围内,在主动脉阻断后开始增高,主动脉开放后2h明显增高,到主动脉开放后12h达到最高值,随后逐渐下降,分别在术后120h、72h接近正常值。2.r Hu EPO预处理可以降低CPB心脏瓣膜置换术中、术后患者血清c Tn I、血清CK-MB的浓度,减轻心肌缺血缺氧和缺血-再灌注损伤,具有心肌保护作用,且有剂量依赖性。3.随着阻断时间的延长心肌细胞超微结构损伤程度越重,r Hu EPO预处理可以减轻心肌细胞超微结构的损伤程度,具有心肌保护作用,且有剂量依赖性。
[Abstract]:Objective: myocardial protection is always a hot spot in the study of open heart surgery for Cardiopulmonary Bypass (CPB). Cardiac dysfunction is associated with primary disease, myocardial ischemia, ischemia-reperfusion injury and surgical trauma at CPB. Ischemia reperfusion injury is an important factor in cardiac muscle injury. Recombinant human erythropoietin (R Hu EPO) plays a protective role in myocardial ischemia-reperfusion injury, but there are few studies on the myocardial protection in the perioperative period of CPB heart surgery. Therefore, this topic has been observed by observing R Hu EPO preconditioning in the perioperative cardiac troponin I (cardiac) Ponin I, C Tn I), the effect of phosphocreatine kinase isoenzyme (creatine kinase-MB, CK-MB), the ultrastructural changes of cardiac myocytes, and to explore the myocardial protection of R Hu EPO pretreatment. Methods: 40 patients with rheumatic heart valve (mitral valve + aortic valve replacement) were selected. There were no metabolic disorders of the liver and kidney, thyroid disease, diabetes and other metabolic disorders, no angina, myocardial infarction, hypertension, and no long-term use of glucocorticoid and severe infectious diseases. The random number table was divided into 1 control groups (group A), 3 experimental groups (B, C, D), 10 cases in each group. In the experimental group, R Hu EPO was injected subcutaneously three days before the operation. The dose of R Hu EPO in the group B was 50u/Kg, the C group was 100u/Kg, the D group was 200u/Kg, and the control group was not treated. All the patients were open to the aorta, open aorta, aorta opening. After the opening of 6h (T3), 12h (T4) after the opening of the aorta, 24h (T5) after the opening of the aorta, 36h (T6) after the opening of the aorta, the 72h (T7) after the opening of the aorta, the 96h (T8) after the opening of the aorta, and the ten time points after the opening of the aorta, the blood routine was detected, the serum concentration was changed, and the obstruction of the aorta was blocked, respectively. Three small pieces of right atrium comb muscle tissue were cut off at the three time points of 30min and 60min after aorta interruption. Results: all patients had no complications during the perioperative period. All the patients were cured and discharged from the hospital. The difference of general data before and during the operation of CPB heart valve replacement in the four groups had no statistical significance (P0.05). Three different doses of R Hu EPO The serum level of C Tn I in the pretreated group and the control group was in the normal range before the induction of anesthesia. After the aorta was blocked, the 2H increased significantly. After the opening of the aorta, the 2H increased significantly. After the opening of the aorta, the 12h reached the highest value, and then gradually decreased. After the operation, the 120h, 72h was close to the normal value. The serum C Tn in each time point in the group was in C Tn. I, serum CK-MB concentration was higher than before induction of anesthesia, the difference was statistically significant (P0.05), while the three different doses of R Hu EPO pretreatment group and the control group were compared with the control group: the R Hu EPO preconditioning group at different doses at each time point serum C Tn I, serum concentration was significantly lower than the control group, and blood C Tn I, serum CK-MB concentration decreased with the increase of R Hu EPO preconditioning dose (P0.05). The difference was statistically significant (P0.05). Changes in the right atrium comb muscle tissue of three different doses of R Hu EPO pretreatment group and control group, and the ultrastructural damage of myoscula, myosum, mitochondria and sarcoplasmic reticulum along with the interruption time The degree of ultrastructural damage of myocytes, myosmus, mitochondria, sarcoplasmic reticulum and other ultrastructural damage decreased with the increase of R Hu EPO preconditioning dose. Conclusion: 1. serum C Tn I, serum CK-MB concentration is in normal range before anesthesia induction, after aorta blockage, the increase of 2H obviously increases, to aorta after aorta is open. After opening, 12h reached the highest value, and then decreased gradually. The pre operation of 120h and 72h near normal value.2.r Hu EPO could reduce the serum C Tn I, serum CK-MB concentration, reduce myocardial ischemia and hypoxia and ischemia-reperfusion injury in the postoperative patients with CPB heart valve replacement, and have the protective effect of myocardial ischemia and reperfusion, and there is a dose dependent.3. along with the resistance. R Hu EPO pretreatment can reduce the damage degree of ultrastructure of myocardial cells, and have myocardial protective effect, and it has a dose dependent manner.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R654.2
本文编号：2126885
[Abstract]:Objective: myocardial protection is always a hot spot in the study of open heart surgery for Cardiopulmonary Bypass (CPB). Cardiac dysfunction is associated with primary disease, myocardial ischemia, ischemia-reperfusion injury and surgical trauma at CPB. Ischemia reperfusion injury is an important factor in cardiac muscle injury. Recombinant human erythropoietin (R Hu EPO) plays a protective role in myocardial ischemia-reperfusion injury, but there are few studies on the myocardial protection in the perioperative period of CPB heart surgery. Therefore, this topic has been observed by observing R Hu EPO preconditioning in the perioperative cardiac troponin I (cardiac) Ponin I, C Tn I), the effect of phosphocreatine kinase isoenzyme (creatine kinase-MB, CK-MB), the ultrastructural changes of cardiac myocytes, and to explore the myocardial protection of R Hu EPO pretreatment. Methods: 40 patients with rheumatic heart valve (mitral valve + aortic valve replacement) were selected. There were no metabolic disorders of the liver and kidney, thyroid disease, diabetes and other metabolic disorders, no angina, myocardial infarction, hypertension, and no long-term use of glucocorticoid and severe infectious diseases. The random number table was divided into 1 control groups (group A), 3 experimental groups (B, C, D), 10 cases in each group. In the experimental group, R Hu EPO was injected subcutaneously three days before the operation. The dose of R Hu EPO in the group B was 50u/Kg, the C group was 100u/Kg, the D group was 200u/Kg, and the control group was not treated. All the patients were open to the aorta, open aorta, aorta opening. After the opening of 6h (T3), 12h (T4) after the opening of the aorta, 24h (T5) after the opening of the aorta, 36h (T6) after the opening of the aorta, the 72h (T7) after the opening of the aorta, the 96h (T8) after the opening of the aorta, and the ten time points after the opening of the aorta, the blood routine was detected, the serum concentration was changed, and the obstruction of the aorta was blocked, respectively. Three small pieces of right atrium comb muscle tissue were cut off at the three time points of 30min and 60min after aorta interruption. Results: all patients had no complications during the perioperative period. All the patients were cured and discharged from the hospital. The difference of general data before and during the operation of CPB heart valve replacement in the four groups had no statistical significance (P0.05). Three different doses of R Hu EPO The serum level of C Tn I in the pretreated group and the control group was in the normal range before the induction of anesthesia. After the aorta was blocked, the 2H increased significantly. After the opening of the aorta, the 2H increased significantly. After the opening of the aorta, the 12h reached the highest value, and then gradually decreased. After the operation, the 120h, 72h was close to the normal value. The serum C Tn in each time point in the group was in C Tn. I, serum CK-MB concentration was higher than before induction of anesthesia, the difference was statistically significant (P0.05), while the three different doses of R Hu EPO pretreatment group and the control group were compared with the control group: the R Hu EPO preconditioning group at different doses at each time point serum C Tn I, serum concentration was significantly lower than the control group, and blood C Tn I, serum CK-MB concentration decreased with the increase of R Hu EPO preconditioning dose (P0.05). The difference was statistically significant (P0.05). Changes in the right atrium comb muscle tissue of three different doses of R Hu EPO pretreatment group and control group, and the ultrastructural damage of myoscula, myosum, mitochondria and sarcoplasmic reticulum along with the interruption time The degree of ultrastructural damage of myocytes, myosmus, mitochondria, sarcoplasmic reticulum and other ultrastructural damage decreased with the increase of R Hu EPO preconditioning dose. Conclusion: 1. serum C Tn I, serum CK-MB concentration is in normal range before anesthesia induction, after aorta blockage, the increase of 2H obviously increases, to aorta after aorta is open. After opening, 12h reached the highest value, and then decreased gradually. The pre operation of 120h and 72h near normal value.2.r Hu EPO could reduce the serum C Tn I, serum CK-MB concentration, reduce myocardial ischemia and hypoxia and ischemia-reperfusion injury in the postoperative patients with CPB heart valve replacement, and have the protective effect of myocardial ischemia and reperfusion, and there is a dose dependent.3. along with the resistance. R Hu EPO pretreatment can reduce the damage degree of ultrastructure of myocardial cells, and have myocardial protective effect, and it has a dose dependent manner.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R654.2
【参考文献】
相关期刊论文 前10条
1 秦川,肖颖彬,钟前进,陈林,王学锋;EPO预处理对心肌缺氧复氧损伤保护作用的研究[J];重庆医学;2005年05期
2 李元敏;宋兵;刘瑞生;唐汉博;;重组人促红细胞生成素对瓣膜置换术患者心肌保护作用[J];临床心血管病杂志;2009年04期
3 付永锋,樊廷俊;Bcl-2家族蛋白与细胞凋亡[J];生物化学与生物物理学报;2002年04期
4 臧伟进;孙蕾;于晓江;;腺苷和乙酰胆碱后适应诱导的心肌保护作用(英文)[J];生理学报;2007年05期
5 张鲁英,姜冠华,张广福,梁家立;婴幼儿温-冷-温停博液灌注心肌的临床研究[J];中国体外循环杂志;2004年03期
6 陈纲;陈张根;贾兵;何春兰;钟慧;;涂层技术对小婴儿体外循环炎性反应的保护作用[J];中国体外循环杂志;2007年04期
7 黑飞龙;龙村;;中国体外循环教育的现状和思考[J];中国体外循环杂志;2014年01期
8 王东侠;谭茗月;;促红细胞生成素在心血管疾病中的应用进展[J];心脏杂志;2007年03期
9 江樊莉;张新金;李建美;;促红细胞生成素抑制心脏重构作用及其机制的研究进展[J];医学综述;2012年02期
10 王萍,房秀生;心肌肌钙蛋白Ⅰ对体外循环期心肌损伤的判定价值[J];中华麻醉学杂志;2000年05期
相关博士学位论文 前1条
1 吴锦波;促红细胞生成素在大鼠心肌缺血再灌注损伤中的保护性作用研究[D];南方医科大学;2009年
，本文编号：2126885
本文链接：https://www.wllwen.com/yixuelunwen/mazuiyixuelunwen/2126885.html
最近更新
教材专著
