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粒细胞集落刺激因子对心肌梗死大鼠炎症与凋亡的影响
Effect of granulocyte colony-stimulating factor on inflammation and apoptosis in rats with myocardial infarction
【摘要】 目的研究粒细胞集落刺激因子(GCSF)对急性心肌梗死大鼠炎症因子及相关凋亡指标的影响。方法按照体重将SD雄性大鼠随机分为4组,每组各15只:假手术组、模型组、GCSF小剂量递增组(GCSF-L-I)与GCSF大剂量组(GCSF-H)。建立心肌梗死动物模型后,GCSF-L-I组大鼠给予GCSF初始剂量5μg·kg-1,随后每天增加剂量5μg·kg-1,连续给药1周,总剂量达140μg·kg-1;GCSF-H组大鼠给予GCSF 20μg·kg-1·d-1,连续给药1周,总剂量亦达140μg·kg-1;假手术组、模型组给予等量0.9%Na Cl。检测各组大鼠的血液细胞学指标、炎症因子指标及心功能指标,建模术后第2周通过免疫印迹法测定各组大鼠相关细胞凋亡因子B细胞淋巴瘤-2(Bcl-2)及B淋巴瘤2-基因相关X蛋白(Bax)表达。结果建模2周,假手术组、模型组、GCSF-L-I组和GCSF-H组的白细胞数量分别为(6.15±0.28),(6.35±0.68),(8.20±1.51),(7.46±2.43)×109/L,模型组与假手术组比较,差异无统计学意义(P>0.05);GCSF-L-I组和GCSF-H组与模型组比较,差异均有统计学意义(均P<0.05)。假手术组、模型组、GCSF-L-I组和GCSF-H组的超敏C反应蛋白分别为(1.25±0.23),(4.16±0.71),(2.00±0.69),(2.12±0.72)mg·L-1,模型组、CSF-L-I组和GCSF-H组与假手术组比较,差异均有统计学意义(均P<0.05);GCSF-L-I组和GCSF-H组与模型组比较,差异均有统计学意义(均P<0.05)。假手术组、模型组、GCSF-L-I组和GCSF-H组的左室射血分数分别为(70.16±2.95)%,(43.36±3.10)%,(65.45±2.23)%,(56.27±2.36)%,模型组与假手术组比较,差异有统计学意义(P<0.05);GCSF-L-I组和GCSF-H组与模型组比较,差异均有统计学意义(均P<0.05);GCSF-L-I组明显高于GCSF-H组,差异有统计学意义(P<0.05)。结论 GCSF通过调控炎症反应、抑制凋亡,明显改善了大鼠心梗后心功能,且GCSF小剂量递增干预效果更明显。
【Abstract】 Objective To study the effect of granulocyte colony-stimulating factor(GCSF)on inflammatory factors and related apoptosis indexes in rats with acute myocardial infarction(AMI).Methods SD rats were randomly divided into 4 groups:sham operation group,model group,low-dose GCSF increasing(GCSF-L-I)group and high-dose GCSF(GCSF-H)group.After the AMI model established,GCSF-L-I group,after coronary artery ligation,intraperitoneally injected GCSF,initial dose 5μg·kg-1,then a daily increase of 5μg·kg-1,continued the medication for a week,the total dose of GCSF was 140μg·kg-1;GCSF-H group,after coronary artery ligation,intraperitoneally injected GCSF 20μg·kg-1·d-1,continued the medication for a week,the total dose of GCSF was also140μg·kg-1;sham operation group and model group were given the same amount of 0.9%sodium chloride injection.The indexes of blood cytology,inflammatory factors and cardiac function were detected at 1 and 2 weeks after modeling in each group.At the time of 2 weeks after modeling,the expression of apoptosis related factors B-cell lymphoma-2(Bcl-2)and BCL2-associated X protein(Bax)were detected by Western blot.Results Two weeks after modeling,the number of white blood cells in sham operation group,model group,GCSF-L-I group and GCSF-H group were respectively(6.15±0.28),(6.35±0.68),(8.20±1.51),(7.46±2.43)×109·L-1;compared with the sham operation group,there was no significant change in the model group(P>0.05);compared with the model group,the GCSF-L-I group and the GCSF-H group were significantly increased(all P<0.05).The high sensitive C-reactive protein levels in the 4 groups were respectively(1.25±0.23),(4.16±0.71),(2.00±0.69),(2.12±0.72)mg·L-1.The left ventricular ejection fraction in the 4 groups were respectively(70.16±2.95)%,(43.36±3.10)%,(65.45±2.23)%,(56.27±2.36)%.Compared the sham operation group with the model group,the difference of the factors were significant(all P<0.05).Compared the model group with the GCSF-L-I group and the GCSF-H group were all significant(all P<0.05).GCSF-L-I group was significantly higher than that in GCSF-H group(P<0.05).Conclusion GCSF significantly improved the cardiac function of rats after myocardial infarction by regulating inflammatory reaction and inhibiting apoptosis,and the effect of low dose increasing of GCSF was more obvious.
【Key words】 acute myocardial infarction; granulocyte colony-stimulating factor; apoptosis; inflammatory factor;
- 【文献出处】 中国临床药理学杂志 ,The Chinese Journal of Clinical Pharmacology , 编辑部邮箱 ,2018年12期
- 【分类号】R-332;R965
- 【被引频次】2
- 【下载频次】112