舒芬太尼联合脐血间充质干细胞移植对梗死心肌的保护作用

背景:药物预处理的延迟性保护作用成为近年来预处理领域的研究热点,舒芬太尼是一种非选择性阿片受体激动剂,有明显的心肌保护作用。目的:探讨舒芬太尼预处理联合脐血间充质干细胞移植对心肌梗死后损伤心肌的保护作用。方法:采用结扎左冠状动脉前降支的方式建立大鼠心肌缺血再灌注模型(缺血30 min,再灌注180 min),建模后随机分为缺血再灌注组,脐血间充质干细胞组,舒芬太尼+脐血间充质干细胞组,每组30只。缺血再灌注组于缺血再灌注前5 min经腹腔静脉注射1 mL生理盐水,脐血间充质干细胞组经腹腔静脉注射脐血间充质干细胞悬液1 m L,舒芬太尼+脐血间充质干细胞组在此基础上于冠脉阻断前10 min经腹腔静脉注射舒芬太尼10μg/kg,治疗后2周进行相关指标检测。结果与结论:(1)心肌梗死面积:舒芬太尼+脐血间充质干细胞组<脐血间充质干细胞组<缺血再灌注组,差异有显著性意义(P<0.05);(2)与缺血再灌注组比较,脐血间充质干细胞组血清肌酸激酶、乳酸脱氢酶及肌钙蛋白Ⅰ水平降低,一氧化氮水平增加,与脐血间充质干细胞组比较,舒芬太尼+脐血间充质干细胞组血清肌酸激酶、乳酸脱氢酶及肌钙蛋白I水平明显降低,一氧化氮水平增加更明显,差异有显著性意义(P<0.05);(3)Caspase-3蛋白表达:舒芬太尼+脐血间充质干细胞组<脐血间充质干细胞组<缺血再灌注组,差异有显著性意义(P<0.05);(4)血流动力学指标:与缺血再灌注组比较,脐血间充质干细胞组、舒芬太尼+脐血间充质干细胞组左心室舒张压升高,左心室舒张末压降低,差异有显著性意义(P<0.05);(5)与缺血再灌注组比较,脐血间充质干细胞组心肌组织病理学损伤程度减轻,舒芬太尼+脐血间充质干细胞组明显减轻;(6)结果表明,舒芬太尼预处理联合脐血间充质干细胞移植能够减轻大鼠心肌梗死程度,保护损伤的心肌。

Sufentanil combined with umbilical cord blood stem cells protects against myocardial infarction

BACKGROUND: In recent years, delayed protection of drug pretreatment has become a hot spot in the field of pretreatment, and sufentanil is a non-selective opioid receptor agonist that plays a significant myocardial protective role. OBJECTIVE:To investigate the protective effect of sufentanil combined with umbilical cord blood stem cell transplantation on injured myocardium after myocardial infarction. METHODS:Myocardial infarction model by ligating the left anterior descending coronary artery (ischemia 30 minutes and reperfusion 180 minutes) was made in 90 healthy adult Wistar rats, and then these rat models were randomly divided into ischemia-reperfusion (IR) group, cell transplantation group, combined treatment group (n=30/group). Rats in the IR group were given intraperitoneally intravenous injection of 1 mL normal saline 5 minutes before IR; rats in the cell transplantation group were given intraperitoneally intravenous injection of 1 mL umbilical cord blood stem cell suspension 5 minutes prior to IR; and rats in the combined treatment group were given intraperitoneally intravenous injection of 10 μg/kg sufentanil 10 minutes before IR and 1 mL umbilical cord blood stem cell suspension 5 minutes prior to IR. Two weeks later, related indicators were detected. RESULTS AND CONCLUSION:Compared with the IR group, myocardial infarct size was reduced significantly in the combined treatment group, followed by the cell transplantation group (P < 0.05). Lowest levels of serum creatine kinase, lactate dehydrogenase and troponin I were obtained in the combined treatment group followed by the cell transplantation group and IR group, while highest level of nitric oxide was observed in the combined treatment group followed by the cell transplantation group and IR group(P < 0.05). Highest expression of Caspase-3 protein was recorded in the combined treatment group, followed by the cell transplantation group and IR group (P < 0.05). Significantly increased left ventricular diastolic blood pressure and decreased left ventricular end diastolic pressure were found in the two cell transplantation groups compared with the IR group (P < 0.05). Moreover, pathological injury of the myocardial tissues was mitigated in the cell transplantation group and significantly relived in the combined treatment group compared with the IR group. In conclusion, the combined use of sufentanil and umbilical cord blood mesenchymal stem cell transplantation can reduce the degree of myocardial infarction and protect against myocardial injury.