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中国科学技术大学附属第一医院心脏大血管外科
纸质出版日期:2022,
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余继全, 阮鹏, 葛建军. 川陈皮素通过Rnd3调控核因子κB信号在心肌梗死中的作用机制研究[J]. 中国医院用药评价与分析, 2022,22(3):332-337.
YU Jiquan, RUAN Peng, GE Jianjun. Mechanism of Nobiletin in Myocardial Infarction Based on Regulation of Nuclear Factor κB Signal by Rnd3[J]. 2022,22(3):332-337.
余继全, 阮鹏, 葛建军. 川陈皮素通过Rnd3调控核因子κB信号在心肌梗死中的作用机制研究[J]. 中国医院用药评价与分析, 2022,22(3):332-337. DOI: 10.14009/j.issn.1672-2124.2022.03.018.
YU Jiquan, RUAN Peng, GE Jianjun. Mechanism of Nobiletin in Myocardial Infarction Based on Regulation of Nuclear Factor κB Signal by Rnd3[J]. 2022,22(3):332-337. DOI: 10.14009/j.issn.1672-2124.2022.03.018.
目的:探讨川陈皮素通过Rnd3抑制核因子κB(NF-κB)信号调控心肌梗死的作用和相关机制。方法:(1)取普通正常小鼠40只,均分为假手术组、心肌梗死手术组、川陈皮素灌胃组和川陈皮素灌胃+心肌梗死手术组,应用心脏超声检测四组小鼠心功能变化,应用蛋白质印迹法检测四组小鼠心脏组织中Rnd3和Cleaved-caspase3的表达变化。(2)在新生大鼠心肌细胞水平进行Rnd3和NF-κB P65的蛋白免疫共沉淀和染色质免疫共沉淀实验,检测Rnd3和P65的结合情况。在新生大鼠心肌细胞中转染Sh-Rnd3和OE-Rnd3慢病毒,以蛋白质印迹法检测NF-κB P65的表达变化。(3)取心肌梗死小鼠40只,均分为造模组、造模+川陈皮素组、造模+NF-κB激动剂组和造模+川陈皮素+NF-κB激动剂组,应用心脏超声检测四组小鼠心功能变化,应用Tunel染色检测四组小鼠心脏组织中凋亡细胞的表达变化;以蛋白质印迹法检测四组小鼠心脏组织中Cleaved-caspase3的表达变化。结果:(1)心脏超声和蛋白质印迹法实验结果显示,与假手术组相比,心肌梗死手术组小鼠心脏射血分数和短轴缩短率明显降低,心脏组织中Rnd3和Cleaved-caspase3的含量显著升高;与心肌梗死手术组相比,川陈皮素灌胃+心肌梗死手术组小鼠心脏射血分数和短轴缩短率明显升高,心脏组织中Rnd3和Cleaved-caspase3的含量显著降低,上述差异均有统计学意义(P<0.05)。(2)蛋白免疫共沉淀和染色质免疫共沉淀实验结果显示,Rnd3可以与NF-κB P65结合调控新生大鼠心肌细胞的凋亡。抑制Rnd3表达时,NF-κB P65表达升高;过表达Rnd3时,NF-κB P65表达降低。(3)与造模组相比,造模+川陈皮素组、造模+NF-κB激动剂组和造模+川陈皮素+NF-κB激动剂组小鼠心脏射血分数和短轴缩短率升高,Cleaved-caspase3表达降低,细胞凋亡减少,差异均有统计学意义(P<0.05)。结论:川陈皮素可通过抑制Rnd3的表达进而激活NF-κB信号通路,减少急性心肌梗死导致的心肌细胞凋亡。
OBJECTIVE: To investigate the effect and related mechanism of nobiletin in myocardial infarction based on regulation of nuclear factor-κB(NF-κB) signal by Rnd3. METHODS:(1) Totally 40 normal mice were selected and divided into four groups: sham surgery group
myocardial infarction(MI) surgery group
nobiletin gavage group and nobiletin gavage +MI surgery group
changes of cardiac function were detected by cardiac ultrasound
changes of expression of Rnd3 and Cleaved-caspase3 in heart tissues of the four groups of mice were detected by Western blotting.(2) Protein immunoprecipitation and chromatin immunoprecipitation assays of Rnd3 and NF-κB P65 were performed at the level of neonatal rat cardiomyocytes to detect the binding of Rnd3 and P65. Sh-Rnd3 and OE-Rnd3 lentiviruses were transfected in neonatal rat cardiomyocytes
and changes of NF-κB P65 were detected by Western blotting.(3) Forty mice with myocardial infarction were divided into the model group
model+nobiletin group
model+NF-κB agonist group and model+nobiletin+NF-κB agonist group
changes of cardiac function in four groups were detected by cardiac ultrasound
and changes of apoptotic cell expression in heart tissues of four groups were detected by Tunel staining; changes of expression of Cleaved-caspase3 in heart tissues of four groups were detected by Western blotting. RESULTS:(1) Results of cardiac ultrasound and Western blotting test showed that the cardiac ejection fraction and short-axis shortening fraction in MI surgery group were significantly lower than those in sham surgery group
the contents of Rnd3 and Cleaved-caspase3 in heart tissues in MI surgery group were significantly higher than those in sham surgery group; compared with the MI surgery group
the cardiac ejection fraction and short-axis shortening fraction were significantly higher in the nobiletin gavage+MI surgery group
the contents of Rnd3 and Cleaved-caspase3 in heat tissues were significantly lower in the nobiletin gavage+MI surgery group
with statistically significant differences(P<0.05).(2) Results of protein immunoprecipitation and chromatin immunoprecipitation assays showed that Rnd3 combined with NF-κB P65 could regulate the apoptosis of neonatal rat cardiomyocytes. When Rnd3 expression was inhibited
the expression of NF-κB P65 increased; when Rnd3 was overexpressed
the expression of NF-κB P65 decreased.(3) Compared with the model group
the cardiac ejection fraction and short-axis shortening fraction increased
Cleaved-caspase3 expression and cell apoptosis decreased in the model+nobiletin group
the model+NF-κB agonist group and the model+nobiletin+NF-κB agonist group
with statistically significant differences(P<0.05). CONCLUSIONS: Nobiletin can reduce myocardial apoptosis induced by acute myocardial infarction by inhibiting Rnd3 expression and activating NF-κB signaling pathway.
川陈皮素Rnd3核因子κB心肌梗死
NobiletinRnd3Nuclear factor-κBMyocardial infarction
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