摘要
目的探讨黄芪多糖抑制异丙肾上腺素诱导大鼠心肌肥厚中Toll样受体4/核因子-κB(TLR4/NF-κB)炎症信号通路的作用机制。方法 60只SD大鼠随机分为6组(每组10只):对照组,异丙肾上腺素组,异丙肾上腺素+黄芪多糖(低、中和高剂量)组,异丙肾上腺素+普萘洛尔组。各给药组连续腹腔注射3周,并于给药1 d后腹腔注射异丙肾上腺素2周。给药3周后,各组动物分别检测全心质量指数(HMI)、左心质量指数(LVMI);取左心室组织进行苏木精—伊红染色法(HE)染色;逆转录-聚合酶链反应(RT-PCR)检测心肌组织心钠素(ANP)和TLR4的mRNA表达;蛋白免疫印迹(Western blot)法检测心肌组织TLR4、p65蛋白(p65)和核因子κB抑制蛋白α(IκBα)的表达;酶联免疫吸附试验(ELISA)法检测血清中TNF-α、IL-6的水平。结果与对照组相比,异丙肾上腺素组大鼠的HMI和LVMI显著增加,ANP、TLR4m RNA表达增加,TLR4、p65的蛋白水平增加和IκBα蛋白水平减少,血清中TNF-α、IL-6明显增加,差异均有统计学意义(P<0.01)。与异丙肾上腺素组相比,黄芪多糖400、800mg/(kg·d)和普萘洛尔40 mg/(kg·d)组HMI和LVMI降低,ANP、TLR4 mRNA和TLR4、p65蛋白和血清中TNF-α、IL-6表达显著降低,IκBα蛋白的表达明显增加(P<0.01)。黄芪多糖200 mg/(kg·d)组ANP、TLR4 mRNA和TLR4、p65蛋白和血清中TNF-α的表达降低(P<0.05,P<0.01),IκBα蛋白的表达增高(P<0.05)。结论黄芪多糖能改善异丙肾上腺素诱导的心肌肥厚,其机制可能与抑制TLR4/NF-κB炎症信号通路有关。
AIM To investigate the inhibitory effect of on myocardial hypertrophy induced by isoproterenol via TLR4/NF-KB inflammation signaling pathway. METHODS Sixty SD rats were randomly assigned to the follow ing six groups （10 rats for each group） ： the control, isoproterenol group, isoproterenol plus astragalus polysaccha ride （low, middle and high dose）, and isoproterenol plus propranolol. Administered groups were injected intraper itoneally for three weeks, and isoproterenol was injected intraperitoneally for two weeks in the next day of each administration. After all administrations were completed, heart mass index （HMI） and left ventricular mass index （LVMI） of rats in each group were calculated, and pathological section was performed by HE staining. The mRNA expression levels of ANP and TLR4 were measured by RT-PCR and the expression of TLR4, p65, and IKBot in the tissue were measured by Western blot. The expression of TNF-αand IL-6 was measured by ELISA. RESULTS Compared to the control group, isoproterenol group showed the increase of HMI and LVMI, mRNA expression of ANP and TLR4 and the protein expression of TLR4, p65 and TNF-α, IL-6. Whereas the expression of IKBα de creased （P 〈0.01）. Compared to isoproterenol group, 400, 800 mg/（kg .d） polysaccharide from Astragali Ra dix and 40 rag/（ kg . d）proprano]ol decreased HMI and LVMI , and could significantly down-regulate the overex pression of ANP mRNA, TLR4 mRNA, TLR4, p65 and TNF-oL, IL-6, and increased the expression of IKBα （P 〈 0. 01 ）. polysaccharide from Astragali Radix 200 mg/（ kg.d） decreased ANP mRNA, TLR4 mRNA , TLR4, p65 and TNF-α expression （P 〈 0.05, P 〈 0. 01 ）, and increased the expression of IKBoL （P 〈 0.05）. CONCLU SIONS Polysaccharide from Astragali Radix has a protective effect on isoproterenol-induced cardiac hypertrophy, which is partially via inhibiting the TLR4/NF-KB signaling pathway.
出处
《中成药》
CAS
CSCD
北大核心
2014年第4期674-679,共6页
Chinese Traditional Patent Medicine
基金
国家自然科学基金(30973898/C190702)
辽宁省自然科学资金项目(201102141)
