Long Xianping,Deng Wenwen,Zhao Ranzun,Wang Dongmei,Zheng Xiaoyu,Shi Bei.Effect of silencing Nrf2 gene on myocardial apoptosis after rat myocardial infarction with bone marrow mesenchymal stem cell transplantation[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(13):1319-1324.
Long Xianping,Deng Wenwen,Zhao Ranzun,Wang Dongmei,Zheng Xiaoyu,Shi Bei.Effect of silencing Nrf2 gene on myocardial apoptosis after rat myocardial infarction with bone marrow mesenchymal stem cell transplantation[J].J Amry Med Univ (J Third Mil Med Univ),2015,37(13):1319-1324.DOI:
Effect of silencing Nrf2 gene on myocardial apoptosis after rat myocardial infarction with bone marrow mesenchymal stem cell transplantation
tation of bone marrow mesenchymal stem cells (MSCs) after RNA-interfered nuclear factor erythroid 2-related factor 2 (Nrf2) on myocardial apoptosis and cardiac function in rats after myocardial infarction (MI). Methods The established MI rat models were randomly divided into MSCs transplantation group with Nrf2 gene silence (Nrf2 interference group
n=12)
MSCs transplantation group with no-load lentivirus modification (Nrf2 normal group
n=12)
and normal saline injection group (control group
n=12). On the 7th day after cell transplantation
the expression of caspase 3 in myocardial tissue was observed with cell immunofluorescence assay. On the 28th day after cell transplantation
pathological changes in myocardial tissues after infarction was evaluated after HE staining
the infarct size was evaluated with TTC staining
the protein expression of Nrf2
Bcl2 and Bax in MI region was detected by Western blotting. Results On the 7th day after cell transplantation
the immunofluorescence results showed that the fluorescence intensity of protein caspase 3 in myocardial tissue was significantly increased in MSCs
Nrf2-/-
group than MSCs
Nrf2+/-
group
and no fluorescence was observed in the control group. On the 28th day after cells transplantation
HE staining results showed that there were obvious myocardial tissue muscle fibers in disorganized arrangement and filaments breakage and infiltration of inflammatory cells in the Nrf2 interference group but the myocardial tissue muscle fibers were well-arranged and less infiltration of inflammatory cells were seen in the Nrf2 normal group. Myocardial TTC staining showed that the myocardial infarct size was (35.30±0.41)% in the Nrf2 interference group
which was significantly higher than that in the Nrf2 normal group [(25.07±0.15)%
P0.05
]
but had no significant difference with the control group [(35.40±0.70)%
P0.05
]
. Western blot results showed that the expression levels of Nrf2 and anti-apoptotic protein Bcl-2 were decreased
while that of pro-apoptotic protein Bax was increased in the Nrf2 interference group than the Nrf2 normal group (P0.05)
but no difference was found in the expression of above molecules between the former group and control (P0.05). The Nrf2 interference group had obviously lower ejection fraction (EF) and larger ventricular volumethan the Nrf2 normal group [EF: (40.83±2.67)% vs (52.35±1.58)%
P0.05; left ventricular end diastolic diameter: 1.090±0.061 vs 0.790 0±0.024 5
left ventricular end systolic diameter: 0.750±0.062 vs 0.610±0.026
]
. Conclusion Transplantation of Nrf2-interfered MSCs suppresses the expression of anti-apoptotic protein while promotes that of pro-apoptotic protein in myocardial infarction zone
and reduces the repair ability of exogenous MSCs for infarcted heart.
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