氨甲酰化促红细胞生成素抗大鼠心脏缺血/再灌注损伤的作用

Effect of carbamylated erythropoietin on cardiac ischemia/reperfusion injury in rats

目的研究氨甲酰化促红细胞生成素(CEPO)抗大鼠心脏缺血/再灌注损伤(MIRI)的作用。方法将雄性Wistar大鼠分为4组,每组10只:正常对照组、假手术组、手术组和CEPO组。正常对照组不接受任何干预措施,假手术组大鼠开胸穿线但不结扎冠状动脉,手术组和CEPO组均接受开胸心肌缺血再灌注手术建立MIRI大鼠模型。造模后,CEPO组在术中腹腔注射CEPO 50μg·kg^(-1),2次/周,持续3周;手术组同期腹腔注射等量0.9%Na Cl。3周后观察大鼠血清心肌酶谱、心肌缺血及梗塞面积、中性粒细胞(PMN)计数和测定髓过氧化物酶(MPO)活性、细胞凋亡率。结果造模后,手术组与假手术组和正常对照组相比,血清中得肌酸激酶(CK)、乳酸脱氢酶(LDH)、谷草转氨酶(AST)与α-羟丁酸脱氢酶(α-HBDH)的活性均显著升高,差异均有统计学意义(均P<0.05)。CEPO组的CK、LDH、GOT和α-HBDH活性显著低于对手术组,差异均有统计学意义(均P<0.05)。CEPO组、手术组的心肌缺血面积百分比分别为(39.97±4.24)%,(52.18±4.56)%;这2组的心肌梗塞面积百分比分别为(21.37±8.22)%,(33.41±4.83)%,组间差异均有统计学意义(均P<0.05)。正常对照组、假手术组、手术组和CEPO组的PMN计数分别为(18±13),(19±12),(212±24),(93±16)个;这4组的MPO活性分别为(0.96±0.19),(0.95±0.28),(3.74±0.43),(1.57±0.24)×103U/100 g;这4组的凋亡率分别为(5.93±1.46)%,(5.84±1.51)%,(34.22±6.87)%,(14.31±2.83)%,手术组与假手术组和正常对照组相比,差异均有统计学意义(均P<0.05);CEPO组与手术组比较,差异均有统计学意义(均P<0.05)。结论 CEPO对MIRI大鼠有改善作用。

Objective To study the effect of carbamylated erythropoietin（ CEPO） on cardiac ischemia/reperfusion injury（ MIRI） in rats.Methods Male Wistar rats were divided into four groups： the normal control group（ n = 10）,sham operation group（ n = 10）,the surgery group（ n = 10） and CEPO group（ n = 10）. The normal control group did not receive any intervention measures; the rats in the sham operation group underwent thoracotomy without ligation of the coronary artery; both the operation group and the CEPO group received open chest myocardial ischemia reperfusion surgery to establish MIRI rat model. After modeling,CEPO group received intraperitoneal injection of CEPO 50μg·kg-1,2 times a week for 3 weeks. The same volume of saline wasinjected into the abdominal cavity in the operation group simultaneously. After 3 weeks,the serum myocardial enzyme spectrum,myocardial ischemic and infarction range,polymorphonuclear neutrophils（ PMN） count,myocardial myeloperoxidase（ MPO） activity and myocardial cells apoptosis rate were observed. Results After establishing model,the crestine phosphokinase（ CK）,lactate dehydrogenase（ LDH） and aspartate aminotransferase（ AST）,α-hydroxybutyric dehydrogenase（ α-HBDH） activity in operation group were significantly higher than in sham operation and normal control group（ all P〈0. 05）. The activities of CK,LDH,AST and α-HBDH in CEPO group were significantly lower than those in the operation group（ P〈0. 05）. The percentage of myocardial ischemic area（ %） in CEPO group was（ 39. 97 ± 4. 24） %,which was significantly lower than that of the operation group（ 52. 18 ± 4. 56） %（ P〈0. 05）.The myocardial infarction area（ %） in CEPO group was（ 21. 37 ± 8. 22） %,which was significantly lower than that of the operation group（ 33. 41 ± 4. 83） %（ P〈0. 05）. The PMN counts in normal control and sham operation groups were（ 18 ± 13） and（ 19 ± 12） point,significantly lower than that of the operation group（ 212 ± 24） point（ P〈0. 05）;the PMN count of the CEPO group was（ 93 ± 16）,significantly lower than that of the operation group（ P〈0. 05）. The activity of MPO in normal control and sham operation groups were（ 0. 96 ± 0. 19）,（ 0. 95 ± 0. 28） × 103 U/100 g respectively,significantly lower than that in the operation group（ 3. 74 ± 0. 43） × 103 U/100 g（ P〈0. 05）; the activity of MPO in CEPO group was（ 1. 57 ± 0. 24） × 103 U/100 g,significantly lower than that in the operation group（ P〈0. 05）. The apoptotic rate of myocardial cells in normal control and sham operation groups were（ 5. 93 ± 1. 46） %and（ 5. 84 ± 1. 51） %,significantly lower than in the surgery group（ 34. 22 ± 6. 87） %（ P〈0. 05）; apoptotic rate of myocardial cells in CEPO group was（ 14. 31 ± 2. 83） %,significantly lower than the surgery group（ P〈0. 05）.Conclusion CEPO had the improvement effect on MIRI rat.