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多巴胺缓解脂多糖/半乳糖胺诱导的小鼠急性肝损伤。

Dopamine alleviated acute liver injury induced by lipopolysaccharide/d-galactosamine in mice.

机构信息

Department of Pathophysiology, Chongqing Medical University, Chongqing, China.

Hospital of Chongqing University of Arts and Sciences, Chongqing, China.

出版信息

Int Immunopharmacol. 2018 Aug;61:249-255. doi: 10.1016/j.intimp.2018.06.004. Epub 2018 Jun 9.

DOI:10.1016/j.intimp.2018.06.004
PMID:29894864
Abstract

Dopamine (DA), a crucial neurotransmitter, not only functions in the central nervous system but also plays important roles in the modulation of inflammation. Several studies suggest that DA might suppress the inflammatory response both in vitro and in vivo. In the present study, the potential effects of DA in a mouse model with lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced acute liver injury were investigated. The results show that DA-treated LPS/D-Gal-exposed mice had reduced incidence of histologic lesions, lower plasma aminotransferases and improved the survival rates compared to LPS/D-Gal-exposed mice. Treatment with DA also suppressed LPS/D-Gal-induced production of TNF-α, phosphorylation of c-jun-N-terminal kinase (JNK), cleavage of caspase-3, up-regulation of hepatic caspase-3, caspase-8, and caspase-9 activities and reduced the count of TUNEL-positive hepatocytes. These data indicate that DA attenuated LPS/D-Gal-induced fulminant liver injury in mice, which implies that DA might have value for the prevention of inflammatory liver disease.

摘要

多巴胺(DA)是一种重要的神经递质,不仅在中枢神经系统中发挥作用,而且在炎症的调节中也起着重要作用。一些研究表明,DA 可能在体外和体内抑制炎症反应。在本研究中,研究了 DA 在脂多糖(LPS)/D-半乳糖胺(D-Gal)诱导的急性肝损伤小鼠模型中的潜在作用。结果表明,与 LPS/D-Gal 暴露的小鼠相比,DA 处理的 LPS/D-Gal 暴露的小鼠组织学病变发生率降低,血浆氨基转移酶降低,生存率提高。DA 治疗还抑制了 LPS/D-Gal 诱导的 TNF-α产生、c-jun-N 末端激酶(JNK)磷酸化、半胱天冬酶-3 的切割、肝半胱天冬酶-3、半胱天冬酶-8 和半胱天冬酶-9 活性的上调,并减少了 TUNEL 阳性肝细胞的计数。这些数据表明,DA 减轻了 LPS/D-Gal 诱导的小鼠暴发性肝损伤,这意味着 DA 可能对预防炎症性肝病具有价值。

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