竹节参苷 I 通过抑制诱导型一氧化氮合酶的表达来提高脓毒症小鼠的存活率。
Tubeimoside I improves survival of mice in sepsis by inhibiting inducible nitric oxide synthase expression.
机构信息
Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Institute of Life Sciences, Chongqing Medical University, Chongqing 400010, China.
Institute of Life Sciences, Chongqing Medical University, Chongqing 400010, China; Department of Medical Laboratory Technology, Chongqing Medical University, Chongqing 400010, China.
出版信息
Biomed Pharmacother. 2020 Jun;126:110083. doi: 10.1016/j.biopha.2020.110083. Epub 2020 Apr 6.
Sepsis is a disease with high mortality rate worldwide and inducible nitric oxide (iNOS) induced vascular hyporeactivity plays a key role in it. There is no effective drug to treat vascular hyporeactivity specifically. Tubeimoside I (TBM) is a triterpenoid saponin isolated from Rhizoma Bolbostemmatis. In this study, we found that 4 mg/kg TBM intraperitoneally injected 1 h before cecal ligation and puncture (CLP) partially improved survival, ameliorated mean arterial pressure (MAP) and enhanced vascular responsiveness to norepinephrine (NE) and KCl in wild-type septic mice. CLP activated TLR4-MyD88-NF-κB-iNOS pathway was also inhibited by TBM both in vitro and in vivo. However, iNOS gene knockout counteracted the protection provided by TBM. We conclude that TBM protects mice in sepsis by reducing excessive NO production through inhibiting the TLR4-MyD88-NF-κB-iNOS pathway. Our study suggests a possible therapeutic application of TBM in sepsis.
脓毒症是一种全球范围内死亡率较高的疾病，诱导型一氧化氮合酶（iNOS）引起的血管低反应性在其中起着关键作用。目前尚无专门治疗血管低反应性的有效药物。 苦碟子甲素（TBM）是从苦碟子中分离得到的一种三萜皂苷。在这项研究中，我们发现腹腔注射 4mg/kg TBM 可在盲肠结扎穿孔（CLP）前 1 小时部分改善存活率，改善平均动脉压（MAP），并增强对去甲肾上腺素（NE）和 KCl 的血管反应性。TBM 还可在体外和体内抑制 CLP 激活的 TLR4-MyD88-NF-κB-iNOS 通路。然而，iNOS 基因敲除则抵消了 TBM 提供的保护作用。我们的结论是，TBM 通过抑制 TLR4-MyD88-NF-κB-iNOS 通路减少过度的 NO 生成，从而保护脓毒症小鼠。我们的研究表明 TBM 在脓毒症治疗中有一定的应用前景。
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