重組人促紅細(xì)胞生成素預(yù)處理在風(fēng)濕性心臟瓣膜病圍手術(shù)期心肌保護(hù)作用的研究
發(fā)布時(shí)間：2018-07-16 15:56
【摘要】：目的:心肌保護(hù)一直是體外循環(huán)(Cardiopulmonary Bypass,CPB)心臟直視手術(shù)研究的熱點(diǎn)。術(shù)后心功能障礙與原發(fā)疾病、CPB時(shí)心肌缺血、缺血-再灌注損傷、手術(shù)創(chuàng)傷等因素有關(guān),缺血-再灌注損傷是心肌損傷的一個(gè)重要因素。有研究報(bào)道重組人促紅細(xì)胞生成素(Recombinant human erythropoietin,r Hu EPO)在心肌缺血-再灌注損傷中具有保護(hù)作用,但對(duì)其在CPB心臟直視手術(shù)圍手術(shù)期心肌保護(hù)作用研究較少。因此,本課題通過(guò)觀察r Hu EPO預(yù)處理對(duì)風(fēng)濕性心臟瓣膜病圍術(shù)期心肌肌鈣蛋白I(cardiac troponin I,c Tn I)、磷酸肌酸激酶同工酶(creatine kinase-MB,CK-MB)、心肌細(xì)胞超微結(jié)構(gòu)改變的影響,探討r Hu EPO預(yù)處理的心肌保護(hù)作用。方法:選擇風(fēng)濕性心臟瓣膜病人(擬行二尖瓣+主動(dòng)脈瓣雙瓣瓣膜置換)40例,年齡40~60歲,術(shù)前心功能II或III級(jí)(NYHA),術(shù)前無(wú)肝腎功能障礙、甲狀腺疾病、糖尿病等代謝障礙性疾病;無(wú)心絞痛、心肌梗死、高血壓等病史;無(wú)長(zhǎng)期使用糖皮質(zhì)激素和嚴(yán)重感染性疾病。采用隨機(jī)數(shù)字表分為1個(gè)對(duì)照組(A組),3個(gè)實(shí)驗(yàn)組(B、C、D組),每組10例。所有患者均在靜吸復(fù)合麻醉、中度低溫和血液中度稀釋下進(jìn)行手術(shù)。實(shí)驗(yàn)組術(shù)前三天每天皮下注射r Hu EPO,B組r Hu EPO每次注射劑量為50u/Kg,C組為100u/Kg,D組為200u/Kg,對(duì)照組(A組)未作特殊處理。所有患者均在麻醉誘導(dǎo)前(T0)、主動(dòng)脈開(kāi)放時(shí)(T1)、主動(dòng)脈開(kāi)放后2h(T2)、主動(dòng)脈開(kāi)放后6h(T3)、主動(dòng)脈開(kāi)放后12h(T4)、主動(dòng)脈開(kāi)放后24h(T5)、主動(dòng)脈開(kāi)放后36h(T6)、主動(dòng)脈開(kāi)放后72h(T7)、主動(dòng)脈開(kāi)放后96h(T8)、主動(dòng)脈開(kāi)放后120h(T9)十個(gè)時(shí)間點(diǎn)采取靜脈血標(biāo)本,分別檢測(cè)血常規(guī)、血清c Tn I、血清CK-MB的濃度變化;分別于阻斷主動(dòng)脈時(shí)、阻斷主動(dòng)脈后30min和阻斷主動(dòng)脈后60min三個(gè)時(shí)間點(diǎn)切取三小塊右心房梳狀肌組織。結(jié)果:所有患者圍手術(shù)期無(wú)并發(fā)癥發(fā)生,均痊愈出院。四組患者CPB心臟瓣膜置換術(shù)前和術(shù)中的一般資料比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。三個(gè)不同劑量r Hu EPO預(yù)處理的實(shí)驗(yàn)組和對(duì)照組患者血清c Tn I、血清CK-MB濃度在麻醉誘導(dǎo)前均處于正常范圍內(nèi),主動(dòng)脈阻斷后開(kāi)始增高,主動(dòng)脈開(kāi)放后2h明顯增高,主動(dòng)脈開(kāi)放后12h達(dá)到最高值,隨后逐漸下降,分別在術(shù)后120h、72h接近正常值。組內(nèi)各時(shí)間點(diǎn)血清c Tn I、血清CK-MB濃度均較麻醉誘導(dǎo)前升高,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。而同一時(shí)間點(diǎn)三個(gè)不同劑量r Hu EPO預(yù)處理的實(shí)驗(yàn)組與對(duì)照組進(jìn)行兩兩組間比較:不同劑量r Hu EPO預(yù)處理組在各時(shí)間點(diǎn)血清c Tn I、血清CK-MB濃度明顯低于對(duì)照組(P0.05),且血清c Tn I、血清CK-MB濃度隨r Hu EPO預(yù)處理劑量的增大而降低,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。三個(gè)不同劑量r Hu EPO預(yù)處理的實(shí)驗(yàn)組和對(duì)照組患者右心房梳狀肌組織的變化,隨著阻斷時(shí)間的延長(zhǎng)心肌細(xì)胞肌絲、肌節(jié)、線粒體、肌漿網(wǎng)等超微結(jié)構(gòu)損傷程度越重,且心肌細(xì)胞肌絲、肌節(jié)、線粒體、肌漿網(wǎng)等超微結(jié)構(gòu)損傷程度隨著r Hu EPO預(yù)處理劑量的增大而減輕。結(jié)論：1.血清c Tn I、血清CK-MB濃度在麻醉誘導(dǎo)前均處于正常范圍內(nèi),在主動(dòng)脈阻斷后開(kāi)始增高,主動(dòng)脈開(kāi)放后2h明顯增高,到主動(dòng)脈開(kāi)放后12h達(dá)到最高值,隨后逐漸下降,分別在術(shù)后120h、72h接近正常值。2.r Hu EPO預(yù)處理可以降低CPB心臟瓣膜置換術(shù)中、術(shù)后患者血清c Tn I、血清CK-MB的濃度,減輕心肌缺血缺氧和缺血-再灌注損傷,具有心肌保護(hù)作用,且有劑量依賴性。3.隨著阻斷時(shí)間的延長(zhǎng)心肌細(xì)胞超微結(jié)構(gòu)損傷程度越重,r Hu EPO預(yù)處理可以減輕心肌細(xì)胞超微結(jié)構(gòu)的損傷程度,具有心肌保護(hù)作用,且有劑量依賴性。
[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.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R654.2
本文編號(hào)：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.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R654.2
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