Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities.
Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities.
复制标题
DOI：
10.1038/srep11822
复制
发表时间：
2015-07-07
影响因子：
4.6
通讯作者：
Fan HY
中科院分区：
文献类型：
--
作者：
Yu C;Qi D;Sun JF;Li P;Fan HY
本研究旨在通过体内注射脂多糖(LPS)和盲肠结扎穿孔(CLP)的方法，以及在体外对内毒素诱导的HK-2细胞的作用，探讨大黄酸对脓毒症所致急性肾损伤的作用及其机制。在组织病理学分析中，大黄酸有效地减轻了肾脏损伤的严重程度。大黄酸能显著降低两种实验性脓毒症小鼠血尿素氮、血肌酐及肿瘤坏死因子α、白介素1β水平。此外，大黄酸还能明显减轻CLP后12 h部分受损巨噬细胞的吞噬功能，减少循环中白细胞的渗出。大黄酸能提高脂多糖刺激的HK-2细胞的存活率，抑制单核细胞趋化蛋白-1和IL-8的释放，并抑制脂多糖刺激的磷酸化的NF-κB p65、IκBα和IKKβ的表达。提示大黄酸对内毒素所致的肾损伤具有保护作用。大黄酸抗内毒素肾损伤的机制可能与其抗炎、免疫调节作用密切相关，其机制可能是通过抑制NF-κB信号通路中相关蛋白的表达和磷酸化，抑制NF-κB p65的转录，从而抑制其活化，从而达到抗炎免疫的目的。这些证据表明，大黄酸对内毒素血症所致的急性肾损伤具有潜在的治疗作用。
This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury.
登录
查看更多内容
DOI：
10.1159/000142934
发表时间：
2008
期刊：
Nephron. Experimental nephrology
影响因子：
--
作者：
Kinsey GR;Li L;Okusa MD
通讯作者：
Okusa MD
DOI：
10.1186/cc10061
发表时间：
2011
期刊：
Critical care (London, England)
影响因子：
--
作者：
Karvellas CJ;Farhat MR;Sajjad I;Mogensen SS;Leung AA;Wald R;Bagshaw SM
通讯作者：
Bagshaw SM
影响因子：
11.8
作者：
Girard, TD;Opal, SM;Ely, EW
通讯作者：
Ely, EW
影响因子：
4.4
作者：
Schultz, MJ;van der Poll, T
通讯作者：
van der Poll, T
DOI：
10.1152/ajprenal.00148.2011
发表时间：
2012-04-01
影响因子：
4.2
作者：
Pessoa de Souza, Ana Carolina C.;Volpini, Rildo A.;Andrade, Lucia
通讯作者：
Andrade, Lucia