黄葵素通过核因子κB信号改善老年糖尿病大鼠心肌缺血再灌注的研究

目的：探讨黄葵素对糖尿病心肌缺血再灌注老年大鼠的影响及其作用机制。方法：将老年大鼠按照简单随机法分为假手术组（只穿线不结扎）、模型组（构建糖尿病心肌缺血再灌注模型）、黄葵素低剂量组（75 mg/kg的黄葵素）、黄葵素高剂量组（150 mg/kg的黄葵素）、抑制剂组（10 mg/kg的核因子κB抑制剂BAY11-7082），高剂量+抑制剂组（150 mg/kg的黄葵素+10 mg/kg BAY11-7082）。观察比较大鼠心功能指标、心肌梗死面积、血清指标含量、心肌细胞凋亡率、心肌组织相关蛋白表达。结果：与模型组比较，黄葵素低剂量、黄葵素高剂量组、抑制剂组、高剂量+抑制剂组大鼠心肌梗死面积、心肌肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、丙二醛（MDA）、原位末端转移酶标记法（Tunel）阳性细胞率、磷酸化核因子κB（p-NF-κB p65）、裂解胱天蛋白酶-3（Cl-caspase-3）、Bcl-2相关X蛋白（Bax）水平均显著降低（均P<0.05），左室射血分数（LVEF）、核因子κB抑制蛋白（IκBα）、B淋巴细胞瘤-2基因（Bcl-2）水平均显著升高（均P<0.05）；与高剂量组比较，高剂量+抑制剂组大鼠心肌梗死面积、cTnT、CK-MB、LDH、MDA、Tunel阳性细胞率、p-NF-κB p65、Cl-caspase-3、Bax水平均显著降低（均P<0.05），LVEF、IκBα、Bcl-2水平均显著升高（均P<0.05）。结论：黄葵素可能通过调节核因子κB信号抑制心肌细胞凋亡、氧化应激改善糖尿病心肌缺血再灌注老年大鼠心功能。

Total flavones of Abelmoschus manihot Ameliorate Myocardial Ischemia-reperfusion Injury in Elderly Diabetic Rats via NF-κB Signaling Pathway

To investigate the effects of total flavones of Abelmoschus manihot(TFA) on myocardial ischemia-reperfusion injury in elderly diabetic rats and reveal the potential mechanism.Methods:The simple random method was used to assign elderly rats into sham(threading without ligature)，model(diabetic myocardial ischemia-reperfusion)，low-and high-dose(75 and 150 mg/kg，respectively) TFA，inhibitor [10 mg/kg nuclear factor κB(NF-κB) inhibitor BAY11-7082]，and high-dose TFA+inhibitor(150 mg/kg TFA+10 mg/kg BAY11-7082) groups.The cardiac function indicators，myocardial infarction area，serum levels of indicators，apoptosis rate of myocardial cells，and expression of related proteins in the myocardial tissue were observed and compared.Results:Compared with the model group，the low-and high-dose TFA，inhibitor，and high-dose TFA+inhibitor groups showed reduced myocardial infarction area，lowered levels of cardiac troponin T(cTnT)，creatine kinase isoenzyme MB(CK-MB)，lactate dehydrogenase(LDH)，and malondialdehyde(MDA)，decreased positive rate of TdT-mediated dUDP nick end labeling(Tunel)，and downregulated protein levels of phosphorylated NF-κB p65(P-NF-κB p65)，cleaved cysteine aspartate proteinase-3(Cl-caspase-3) and B-cell lymphoma 2(Bcl-2)-associated X protein(Bax)(all P<0.05).Meanwhile，these groups showcased increased left ventricular ejection fraction(LVEF) and upregulated protein levels of nuclear factor κB inhibitory protein(IκBα) and Bcl-2(all P<0.05).Compared with the high-dose TFA group，the high-dose TFA+inhibitor group presented decreased myocardial infarction area，lowered levels of cTnT，CK-MB，LDH，and MDA，reduced Tunel positive cell rate，downregulated protein levels of p-NF-κB p65，Cl-caspase-3，and Bax(all P<0.05)，increased LVEF，and upregulated protein levels of IκBα and Bcl-2(all P<0.05).Conclusion:TFA may inhibit myocardial apoptosis and oxidative stress and improve the cardiac function in elderly diabetic rats with myocardial ischemia-reperfusion by regulating the NF-κB signaling pathway.