The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced m...The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced myocardial remodeling by activating the PI3K/AKT1 pathway.The cardiac function of mice was evaluated by echocardiography,revealing that MgIG could improve left ventricular function.Pathological staining analysis showed that MgIG could reduce the degree of myocardial injury caused by ISO.Serum data detected by ELISA demonstrated that MgIG could decrease the levels of CK-MB,MDA,and LDH while increasing the activity of GSH-Px.Western blotting analysis revealed that protein expression levels of Collagen I,BNP,Bax,cleaved caspase-3,p-PI3K,and p-AKT1 were decreased,whereas the protein expressions of Bcl-2,COX2,and SOD1 were increased upon MgIG treatment.However,the activation of the PI3K pathway reversed the cardioprotective effects of MgIG,as evidenced by the addition of PI3K activators.Taken together,our comprehensive results suggested that MgIG could improve ISO-induced myocardial remodeling,potentially through its mechanism of inhibiting the PI3K/AKT1 pathway to regulate apoptosis and oxidative stress.展开更多
[目的]基于PI3K/Akt1通路探讨补气养血通络组方对硼替佐米(Vel)所致大鼠周围神经毒性(BiPN)的作用,明确其作用机制。[方法]选取36只成年雄性SD大鼠,随机分为空白组,硼替佐米组(Vel组)、甲钴胺组、补气养血通络组低、中、高剂量组,每组6...[目的]基于PI3K/Akt1通路探讨补气养血通络组方对硼替佐米(Vel)所致大鼠周围神经毒性(BiPN)的作用,明确其作用机制。[方法]选取36只成年雄性SD大鼠,随机分为空白组,硼替佐米组(Vel组)、甲钴胺组、补气养血通络组低、中、高剂量组,每组6只。除空白组外,其余各组大鼠皮下注射硼替佐米(1 mg/kg)每周给药2次持续给药32 d建立BiPN大鼠模型。同时甲钴胺组给予甲钴胺与0.9%氯化钠注射液混悬液(0.05 mg/mL)灌胃;补气通络养血汤低、中、高剂量组给予1.0 g/mL、2.5 g/mL、4.0 g/mL的补气通络养血汤灌胃;空白组及Vel组给予0.9%氯化钠注射液灌胃。通过行为学检测大鼠冷刺激敏感度与机械性缩足阈值;通过HE染色分析大鼠背根神经节病理变化;使用酶联免疫吸附实验(ELISA)检测大鼠血清中SIRT3、IL-6、TNF-α水平以及实时荧光定量聚合酶链反应(RT-qPCR)检测大鼠脊髓中PI3K、Akt1、mTOR mRNA相对表达量。[结果]给药17 d,补气通络养血汤高剂量组冷刺激敏感度与机械性缩足阈值高于Vel组(17.83±2.01 vs 14.17±1.34;6.26±0.64 vs 5.38±0.28;P<0.05)。给药25 d,与Vel组相比,甲钴胺组和补气通络养血汤高剂量组冷刺激敏感度与机械性缩足阈均升高(P<0.05)。给药32 d,与Vel组相比,甲钴胺组、补气通络养血汤(中、高剂量)组冷刺激敏感度与机械性缩足阈均升高(P<0.05);与空白组相比,Vel组SIRT3水平降低,IL-6及TNF-α水平升高(116.73±5.39 vs 77.68±4.17;78.42±6.36 vs 104.27±7.28;40.03±8.36 vs 97.29±10.68;P<0.05)。与Vel组相比,甲钴胺组及补气通络养血汤(低、中、高剂量组)背根神经节损伤逐渐恢复、SIRT3水平均有所上升、IL-6及TNF-α水平均降低,但仅甲钴胺组、补气通络养血汤(中、高剂量组)与Vel组相比具有统计意义(P<0.05);与空白组相比,Vel组PI3K、AKT1、mTOR mRNA相对表达量均降低(2.89±0.84 vs 0.72±0.41;2.77±0.54 vs 0.62±0.61;2.93±0.68 vs 0.71±0.56;P<0.05)。与Vel组相比,甲钴胺组、补气通络养血汤(中、高剂量组)PI3K、AKT1、mTOR mRNA相对表达量均升高,差异具有统计意义(P<0.05)。[结论]补气养血通络汤可通过抑制炎症因子,上调PI3K/Akt1通路,改善硼替佐米所致的大鼠周围神经毒性损伤。展开更多
基金Jiangxi Provincial Department of Education Science and Technology Project(Grant No.GJJ2401615)Jiangxi Provincial Department of Education Teaching Reform Project(Grant No.JXJG-24-15-15).
文摘The aim of this study is to investigate the mechanism of magnesium isoglycyrrhizinate(MgIG)in the treatment of myocardial remodeling induced by isoproterenol(ISO)in mice.We assessed the impact of MgIG on ISO-induced myocardial remodeling by activating the PI3K/AKT1 pathway.The cardiac function of mice was evaluated by echocardiography,revealing that MgIG could improve left ventricular function.Pathological staining analysis showed that MgIG could reduce the degree of myocardial injury caused by ISO.Serum data detected by ELISA demonstrated that MgIG could decrease the levels of CK-MB,MDA,and LDH while increasing the activity of GSH-Px.Western blotting analysis revealed that protein expression levels of Collagen I,BNP,Bax,cleaved caspase-3,p-PI3K,and p-AKT1 were decreased,whereas the protein expressions of Bcl-2,COX2,and SOD1 were increased upon MgIG treatment.However,the activation of the PI3K pathway reversed the cardioprotective effects of MgIG,as evidenced by the addition of PI3K activators.Taken together,our comprehensive results suggested that MgIG could improve ISO-induced myocardial remodeling,potentially through its mechanism of inhibiting the PI3K/AKT1 pathway to regulate apoptosis and oxidative stress.
文摘[目的]基于PI3K/Akt1通路探讨补气养血通络组方对硼替佐米(Vel)所致大鼠周围神经毒性(BiPN)的作用,明确其作用机制。[方法]选取36只成年雄性SD大鼠,随机分为空白组,硼替佐米组(Vel组)、甲钴胺组、补气养血通络组低、中、高剂量组,每组6只。除空白组外,其余各组大鼠皮下注射硼替佐米(1 mg/kg)每周给药2次持续给药32 d建立BiPN大鼠模型。同时甲钴胺组给予甲钴胺与0.9%氯化钠注射液混悬液(0.05 mg/mL)灌胃;补气通络养血汤低、中、高剂量组给予1.0 g/mL、2.5 g/mL、4.0 g/mL的补气通络养血汤灌胃;空白组及Vel组给予0.9%氯化钠注射液灌胃。通过行为学检测大鼠冷刺激敏感度与机械性缩足阈值;通过HE染色分析大鼠背根神经节病理变化;使用酶联免疫吸附实验(ELISA)检测大鼠血清中SIRT3、IL-6、TNF-α水平以及实时荧光定量聚合酶链反应(RT-qPCR)检测大鼠脊髓中PI3K、Akt1、mTOR mRNA相对表达量。[结果]给药17 d,补气通络养血汤高剂量组冷刺激敏感度与机械性缩足阈值高于Vel组(17.83±2.01 vs 14.17±1.34;6.26±0.64 vs 5.38±0.28;P<0.05)。给药25 d,与Vel组相比,甲钴胺组和补气通络养血汤高剂量组冷刺激敏感度与机械性缩足阈均升高(P<0.05)。给药32 d,与Vel组相比,甲钴胺组、补气通络养血汤(中、高剂量)组冷刺激敏感度与机械性缩足阈均升高(P<0.05);与空白组相比,Vel组SIRT3水平降低,IL-6及TNF-α水平升高(116.73±5.39 vs 77.68±4.17;78.42±6.36 vs 104.27±7.28;40.03±8.36 vs 97.29±10.68;P<0.05)。与Vel组相比,甲钴胺组及补气通络养血汤(低、中、高剂量组)背根神经节损伤逐渐恢复、SIRT3水平均有所上升、IL-6及TNF-α水平均降低,但仅甲钴胺组、补气通络养血汤(中、高剂量组)与Vel组相比具有统计意义(P<0.05);与空白组相比,Vel组PI3K、AKT1、mTOR mRNA相对表达量均降低(2.89±0.84 vs 0.72±0.41;2.77±0.54 vs 0.62±0.61;2.93±0.68 vs 0.71±0.56;P<0.05)。与Vel组相比,甲钴胺组、补气通络养血汤(中、高剂量组)PI3K、AKT1、mTOR mRNA相对表达量均升高,差异具有统计意义(P<0.05)。[结论]补气养血通络汤可通过抑制炎症因子,上调PI3K/Akt1通路,改善硼替佐米所致的大鼠周围神经毒性损伤。
