Yohimbine enhances protection of berberine against LPS-induced mouse lethality through multiple mechanisms.
Yohimbine enhances protection of berberine against LPS-induced mouse lethality through multiple mechanisms.
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育亨宾通过多种机制增强小檗碱对脂多糖引起的小鼠致死的保护
DOI：
10.1371/journal.pone.0052863
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Li H;Wang Y;Zhang H;Jia B;Wang D;Li H;Lu D;Qi R;Yan Y;Wang H
脓毒症仍然是重症监护病房死亡的主要原因，迫切需要更好的治疗方法。革兰氏阴性细菌脂多糖(LPS)是脓毒症的重要诱因。我们已经证明，黄连素(Ber)对脂多糖(LPS)诱导的致死性具有保护作用，育亨宾(Yohimbine，Y)可增强其致死性，Ber与育亨宾(Yohimbine，Y)联合应用也可提高败血症小鼠的存活率。然而，Y增强Ber对脂多糖诱导的致死性保护的确切机制仍不清楚。本研究证实，同时给予Y也增强了Ber对抗内毒素致死的保护作用。Ber或/和Y可减轻内毒素攻击小鼠的肝损伤，但不能减轻肾损伤。Ber和/或Y均能抑制脂多糖刺激的IκBα、JNK和ERK的磷酸化、核因子κB的活化和α的产生。Ber或/和Y均能抑制内毒素诱导的小鼠脾细胞IRF3、TYK2和STAT1的磷酸化，抑制β和IP-10mRNA的表达。尤其是Y可增强Ber对脂多糖诱导的IP-10mRNA表达的抑制作用。体外实验进一步证明，Y可显著增强Ber对脂多糖诱导的巨噬细胞产生肿瘤坏死因子-α的抑制作用，Ber与Y联用可促进内毒素诱导的巨噬细胞产生IL-10，并可抑制内毒素刺激的巨噬细胞I-κBα、JNK、ERK和IRF3的磷酸化及核因子-κB的活化。综上所述，Y可通过减轻肝损伤、上调IL-10的产生、抑制IκBα、JNK、ERK和IRF3的磷酸化来增强Ber对脂多糖诱导的小鼠致死性损伤的保护作用。BER联合Y可能是一种预防脓毒症的有效免疫调节剂。
Sepsis remains a major cause of mortality in intensive care units, better therapies are urgently needed. Gram-negative bacterial lipopolysaccharide (LPS) is an important trigger of sepsis. We have demonstrated that berberine (Ber) protects against lethality induced by LPS, which is enhanced by yohimbine (Y) pretreatment, and Ber combined with Y also improves survival in septic mice. However, the precise mechanisms by which Y enhances protection of Ber against LPS - induced lethality remain unclear. The present study confirmed that simultaneously administered Y also enhanced protection of Ber against LPS-induced lethality. Ber or/and Y attenuated liver injury, but not renal injury in LPS-challenged mice. Ber or/and Y all inhibited LPS-stimulated IκBα, JNK and ERK phosphorylation, NF-κB activation as well as TNF-α production. Ber also increased IL-10 production in LPS-challenged mice, which was enhanced by Y. Furthermore, Ber or/and Y all suppressed LPS-induced IRF3, TyK2 and STAT1 phosphorylation, as well as IFN-β and IP-10 mRNA expression in spleen of mice at 1 h after LPS challenge. Especially, Y enhanced the inhibitory effect of Ber on LPS-induced IP-10 mRNA expression. In vitro experiments further demonstrated that Y significantly enhanced the inhibitory effect of Ber on TNF-α production in LPS-treated peritoneal macrophages, Ber combined with Y promoted LPS-induced IL-10 production and LPS-stimulated IκBα, JNK, ERK and IRF3 phosphorylation and NF-κB activation were also suppressed by Ber or/and Y pretreatment in peritoneal macrophages. Taken together, these results demonstrate that Y enhances the protection of Ber against LPS-induced lethality in mice via attenuating liver injury, upregulating IL-10 production and suppressing IκBα, JNK, ERK and IRF3 phosphorylation. Ber combined with Y may be an effective immunomodulator agent for the prevention of sepsis.
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影响因子：
5.6
作者：
Ponte, Charlene Barreto;Rocha Alves, Erica Alessandra;Souza Kueckelhaus, Selma Aparecida
通讯作者：
Souza Kueckelhaus, Selma Aparecida
DOI：
10.1016/s0006-291x(03)01049-0
发表时间：
2003-07-11
影响因子：
3.1
作者：
Sakaguchi, S;Negishi, H;Taniguchi, T
通讯作者：
Taniguchi, T
白介素10可保护小鼠免受致命性内毒素血症的侵害。
影响因子：
15.3
作者：
Howard, M;Muchamuel, T;Andrade, S;Menon, S
通讯作者：
Menon, S
影响因子：
4.4
作者：
Kamezaki, K;Shimoda, K;Harada, M
通讯作者：
Harada, M
DOI：
10.1073/pnas.92.23.10688
发表时间：
1995-11-07
影响因子：
11.1
作者：
LAUBACH, VE;SHESELY, EG;SHERMAN, PA
通讯作者：
SHERMAN, PA