CAJ | 학술논문

背景:近期报道骨髓间充质干细胞心肌内直接移植联合培哚普利治疗急性心肌梗死大鼠,可改善心肌组织内环境,并增强急性心肌梗死疗效.目的:观察人脐血单个核细胞静脉移植联合血管紧张素转化酶抑制剂培哚普利对家兔急性心肌梗死心肌组织炎症反应与促炎因子白细胞介素6表达及心功能影响,并探讨联合治疗对急性心肌梗死可能的保护机制.方法:人脐血单个核细胞取自健康足月分娩产妇脐血.60只健康家兔制备急性心肌梗死模型,建模成功后随机数字表法均分对照组、培哚普利组、单纯移植组和联合治疗组.每组随机选5只家兔分别于移植后1,2,4周超声心动图检测家兔心功能指标左室射血分数及左室短轴缩短率;苏木精-伊红染色光镜观察心肌病理变化和白细胞计数;免疫组化检测心肌组织白细胞介素6蛋白表达量;荧光显微镜观测绿色荧光蛋白阳性细胞.结果与结论:①与对照组比较,培哚普利组、单纯移植组、联合治疗组治疗后1,2,4周心功能指标左室短轴缩短率及左室射血分数改善(P<0.05),单纯移植组高于培哚普利组(P<0.05),联合治疗组改善最显著(P<0.05).②与对照组比较,培哚普利组、单纯移植组、联合治疗组治疗后1,2,4周心肌组织白细胞计数及白细胞介素6的表达均显著减低(P<0.05),且单纯移植组低于培哚普利组(P<0.05),联合治疗组最低(P<0.05).③联合治疗组、单纯移植组治疗后1,2,4周均可见绿色荧光蛋白阳性细胞散在分布于梗死周边区域,且联合治疗组细胞计数多于单纯移植组(P<0.05).说明培哚普利联合人脐血单个核细胞静脉移植治疗急性心肌梗死实验动物,能提高移植细胞在心肌组织内存活率,并进一步改善心功能.其机制可能与联合治疗抑制心肌局部炎症反应及促炎因子白细胞介素6水平表达作用增强有关.
배경:근기보도골수간충질간세포심기내직접이식연합배타보리치료급성심기경사대서,가개선심기조직내배경,병증강급성심기경사료효.목적:관찰인제혈단개핵세포정맥이식연합혈관긴장소전화매억제제배타보리대가토급성심기경사심기조직염증반응여촉염인자백세포개소6표체급심공능영향,병탐토연합치료대급성심기경사가능적보호궤제.방법:인제혈단개핵세포취자건강족월분면산부제혈.60지건강가토제비급성심기경사모형,건모성공후수궤수자표법균분대조조、배타보리조、단순이식조화연합치료조.매조수궤선5지가토분별우이식후1,2,4주초성심동도검측가토심공능지표좌실사혈분수급좌실단축축단솔;소목정-이홍염색광경관찰심기병리변화화백세포계수;면역조화검측심기조직백세포개소6단백표체량;형광현미경관측록색형광단백양성세포.결과여결론:①여대조조비교,배타보리조、단순이식조、연합치료조치료후1,2,4주심공능지표좌실단축축단솔급좌실사혈분수개선(P<0.05),단순이식조고우배타보리조(P<0.05),연합치료조개선최현저(P<0.05).②여대조조비교,배타보리조、단순이식조、연합치료조치료후1,2,4주심기조직백세포계수급백세포개소6적표체균현저감저(P<0.05),차단순이식조저우배타보리조(P<0.05),연합치료조최저(P<0.05).③연합치료조、단순이식조치료후1,2,4주균가견록색형광단백양성세포산재분포우경사주변구역,차연합치료조세포계수다우단순이식조(P<0.05).설명배타보리연합인제혈단개핵세포정맥이식치료급성심기경사실험동물,능제고이식세포재심기조직내존활솔,병진일보개선심공능.기궤제가능여연합치료억제심기국부염증반응급촉염인자백세포개소6수평표체작용증강유관.
BACKGROUND:A recent study has indicated that angiotensin-converting enzyme inhibitor, perindopril, combined with transplantation of bone marrow-derived mesenchymal stem cel s can reduce inflammatory response in the injured myocardium associated with enhanced improvement of cardiac function in an animal model of acute myocardial infarction. OBJECTIVE:To observe the effects of intravenous transplantation of human umbilical cord blood mononuclear cel s combined with perindopril on the inflammatory responses and pro-inflammatory cytokine interleukin-6 expression as wel as the cardiac function in rabbits with acute myocardial infarction, and to investigate the possible protective mechanism of the combination treatment for acute myocardial infarction. METHODS:The human umbilical cord blood mononuclear cel s were obtained from healthy ful-term delivery maternal cord blood. Sixty healthy rabbits were selected to establish the models of acute myocardial infarction, and the models were divided into four groups randomly:control group, perindopril group, simple transplantation group and combination group. Five rabbits were selected from each group to detect the cardiac function index of left ventricular ejection fraction and left ventricular fractional shortening with echocardiography at 1, 2 and 4 weeks after treatment. Hematoxylin-eosin staining was performed to observe the myocardial pathological changes and white blood cel count under light microscope. The protein expression of interleukin-6 in myocardial tissue was detected with immunohistochemistry. The number of green fluorescent protein-positive cel s was observed under fluorescence microscope. RESULTS AND CONCLUSION:Compared with the control group, left ventricular ejection fraction and left ventricular fractional shortening were significantly improved in the perindopril group, simple transplantation group and combination group at 1, 2 and 4 weeks respectively after the treatment (P<0.05). The improvement of cardiac function index in simple transplantation group was higher than that in the perindopril group and most significantly in the combination group among the three treatment groups (P<0.05). Compared with the control group, the number of white blood cel s and the expression of interleukin-6 were decreased significantly in the perindopril group, simple transplantation group and combination group (P<0.05). The number of white blood cel s and the expression of interleukin-6 were lower in the simple transplantation group than in the perindopril group (P<0.05), and lowest in the combination group among the three treatment groups (P<0.05). Green fluorescent protein-positive cel s were found to distribute in the peri-myocardial infarction area in the simple transplantation group and combination group at 1, 2 and 4 weeks after treatment, and the number of the green fluorescent protein-positive cel s in the combination group was more than that in the simple transplantation group. The findings indicate that the combination of intravenous transplantation of human umbilical cord blood mononuclear cel s and perindopril in the treatment of rabbits with acute myocardial infarction can increase the survival rate of transplanted cel s, and further enhance the improvement of the heart function. The possible mechanism may be relate to the combination treatment, which can inhibit the local myocardial inflammation response and the expression of pro-inflammatory cytokine, interleukin-6, effectively.