摘要
目的:探讨microRNA-21对低温条件下心力衰竭大鼠的影响。方法:利用阿霉素及气候箱建立常/低温条件下心力衰竭大鼠模型,以心功能、心肌组织凋亡率及病理改变作为建模成功的观察指标。采用定量荧光PCR(qRT-PCR)检测各组心肌组织microRNA-21的表达。体外培养新生大鼠心肌细胞,标记BrdU,构建过表达microRNA-21的重组慢病毒表达载体并转染入心肌细胞。建模成功后将低温条件下心力衰竭的大鼠随机分为3组,分别注射转染了过表达microRNA-21的重组慢病毒表达载体的心肌细胞(I组)、单纯心肌细胞(II组)和DMEM培养基(III组)。超声心动图检测各组心功能。处死大鼠,留取心脏标本进行HE病理染色及免疫组化检测。结果:低温条件下心力衰竭大鼠(d组)的心功能低于常温条件下心力衰竭大鼠(c组);c组明显低于常温条件下正常大鼠(a组)。a组的心功能与低温条件下正常大鼠(b组)无明显差异。d组的心肌组织凋亡率高于c组;c组明显高于a组。a组的心肌组织凋亡率与b组无明显差异。microRNA-21在c组心肌组织中的表达低于a组;microRNA-21在d组心肌组织中的表达低于c组;microRNA-21在b组心肌组织中的表达低于a组;Ⅰ组microR-NA-21的表达高于Ⅱ组(P<0.05);超声检测心功能提示I组和II组的心功能障碍轻于III组(P<0.05),尤以I组更显著(P<0.05);免疫组化检测显示,移植的心肌细胞在移植区存活;HE染色显示I组和II组的心力衰竭病理变化比Ⅲ组明显减轻(P<0.05),尤以I组更显著(P<0.05)。结论:心肌细胞移植于低温条件下心力衰竭大鼠能改善心功能,减轻心肌组织的心衰病理变化,其中microRNA-21转染入心肌细胞后移植效果更显著,为microRNA-21未来诊断及治疗低温条件下心力衰竭提供了新思路。
AIM： To investigate the effects of microRNA-21 on heart failure rats under the low-temperature condition. METHODS ： The rat model of heart failure was constructed by injection of adriamycin and the rats were placed in a climate box. The cardiac functions, the apoptotic index and pathological changes of the myocardium were determined. The expression of microRNA-21 in the myocardium of the rats was detected by qRT-PCR. Neonatal cardiomyocytes were cultured in vitro, labeled with BrdU and transferred with lenti-microRNA-21 by DNA transfection. The heart failure rats in the cold environment were randomly divided into 3 groups： the rats in group I were transplanted with lenti-microRNA-21- transfected neonatal cardiomyocytes, the rats in group II were transplanted with untransfected cardiomyocytes and the rats in group III were transplanted with culture medium into the failure myocardium. The echocardiography was applied to evaluate the heart functions. The rats were then executed and the hearts were harvested for histological （HE staining） and immuno- histological （anti-BrdU staining） examinations. RESULTS： The cardiac functions of the heart failure rats in the cold envi-ronment （group d） were significantly worse than those in the normal environment （group c）. The cardiac functions in group c were significantly worse than those in the normal rats in the normal environment （group a）. No obvious difference of the cardiac functions between group a and group b （the normal rats in the cold environment） was observed. The apoptot- ic index of the myocardium in group d was significantly higher than that in group c, and that in group c was significantly higher than that in group a. No obvious difference of the apoptotic index of myocardium between group a and group b was found. The expression level of microRNA-21 in the myocardium in group c was significantly lower than that in group a, that in group d was lower than that in group c, and that in group b was also lower than that in group A. The expression of mi- croRNA-21 in the transfected groups was higher than that in untransfected groups. Improvement of ejection fraction （EF） in group I and group II was greater than that in group III. The transplanted cardiomyocytes survived in the failure myocardi- urn. The pathological changes of the myocardium in group I and group II were improved as compared with those in group III. The cardiac functions and pathological improvement in the myocardium were better in group I than those in group II. CONCLUSION： Transplantation of microRNA-21-transfected cardiomyocytes into the myocardium of heart failure rats un- der the low-temperature condition improves the cardiac functions and relieves the pathological changes.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2013年第1期1-8,共8页
Chinese Journal of Pathophysiology
基金
国家科技支撑计划(No.2008BAI68BA02)
