CAJ | 학술논문

目的观察二氧化铈(CeO2)纳米颗粒预处理对缺血再灌注损伤大鼠心肌细胞凋亡相关基因B淋巴细胞/白血病-2(bcl-2)、bcl-2相关X蛋白(bax)、半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3 mRNA表达的影响.方法将40只健康SD雄性大鼠随机分为5组,即假手术组(Sham,n=8)、心肌缺血再灌注损伤模型组(L/R,n=8)、I/R+CeO2不同纳米粒径组(1～10、10～25、50 nm,n=24).建立在体大鼠心肌缺血再灌注损伤模型.采用苏木素-伊红(HE)染色法观察心肌细胞病理学改变;原位末端转移酶标记(TUNEL)法检测心肌细胞凋亡情况;逆转录-聚合酶链反应(RT-PCR)法测定凋亡相关基因bcl-2、bax、Caspase-3 mRNA表达水平.结果与Sham组比较,I/R组和I/R+CeO2不同纳米粒径组均出现明确的心肌缺血和心肌梗死区域;I/R+ CeO2(10～25 nm)组心肌细胞损伤程度最轻,细胞凋亡率显著低于I/R组(P＜0.01);I/R+ CeO2不同纳米粒径组心肌细胞中bcl-2 mRNA表达水平较I/R组显著升高(P＜0.01),bax和Caspase-3 mRNA表达水平较I/R组明显降低(P＜0.01).结论 CeO2纳米颗粒能够一定程度抑制缺血再灌注损伤诱导的心肌细胞凋亡作用,其中10 ～25 nm CeO2纳米颗粒对心肌组织的保护作用最显著.抗凋亡机制可能与其上调抗凋亡基因bcl-2和下调促凋亡基因bax、Caspase-3的表达有关.
목적 관찰이양화시(CeO2)납미과립예처리대결혈재관주손상대서심기세포조망상관기인B림파세포/백혈병-2(bcl-2)、bcl-2상관X단백(bax)、반광안선천동안산특이성단백매(Caspase)-3 mRNA표체적영향.방법 장40지건강SD웅성대서수궤분위5조,즉가수술조(Sham,n=8)、심기결혈재관주손상모형조(L/R,n=8)、I/R+CeO2불동납미립경조(1～10、10～25、50 nm,n=24).건립재체대서심기결혈재관주손상모형.채용소목소-이홍(HE)염색법관찰심기세포병이학개변;원위말단전이매표기(TUNEL)법검측심기세포조망정황;역전록-취합매련반응(RT-PCR)법측정조망상관기인bcl-2、bax、Caspase-3 mRNA표체수평.결과 여Sham조비교,I/R조화I/R+CeO2불동납미립경조균출현명학적심기결혈화심기경사구역;I/R+ CeO2(10～25 nm)조심기세포손상정도최경,세포조망솔현저저우I/R조(P＜0.01);I/R+ CeO2불동납미립경조심기세포중bcl-2 mRNA표체수평교I/R조현저승고(P＜0.01),bax화Caspase-3 mRNA표체수평교I/R조명현강저(P＜0.01).결론 CeO2납미과립능구일정정도억제결혈재관주손상유도적심기세포조망작용,기중10 ～25 nm CeO2납미과립대심기조직적보호작용최현저.항조망궤제가능여기상조항조망기인bcl-2화하조촉조망기인bax、Caspase-3적표체유관.
Objective To investigate the effect of cerium oxide (CeO2) nanoparticles on cardiomyocyte apoptosis,and expression of B lymphocytes/leukemia-2 (bcl-2),bcl-2 associated X protein (bax) and Caspase-3 mRNA following myocardial ischemia-reperfusion injury (MIRI) in rats.Methods Forty health male Sprague-Dawley rats were randomly divided into five groups:sham group,I/R group,I/R + CeO2 preconditioning groups with three diverse nano size (1-10,10-25,50 nm).The MIRI model of rats in vivo was established successfully.Hematoxylin-eosin staining (HE) method was used to identify the pathologic changes of myocardial tissue.The apoptotic cardiomyocytes were detected by in situ TdT-media-ted dUTP nick end labeling (TUNEL) method,and the mRNA expression levels of bcl-2,bax and Caspase-3 were detected by using reverse transcription polymerase chain reaction (RT-PCR).Results Compared with the sham group,myocardial ischemia and myocardial infarction areas were significantly increased in I/R group and I/R + CeO2 preconditioning groups.The apoptosis rate of cardiomyocytes in I/R + CeO2 (10-25 nm) group was significantly decreased (P ＜ 0.01 or P ＜ 0.05) as compared other groups except the Sham group.Compared with the I/R group,the mRNA expression level of bcl-2 was increased (P ＜0.01) and that of bax and Caspase-3 was significantly decreased (P ＜ 0.01) in the I/R + CeO2 precondi-tioning groups.Conclusion CeO2 nanoparticles can inhibit the apoptosis of myocardium induced by MIRI,probably through the mechanisms of up-regulating the expression of bcl-2 and down-regulating the expression of bax and Caspase-3.The 10-25 nm CeO2 nanoparticles show the most significant myocardial protective effect.