小鼠内毒素休克急性期B1和B2激肽受体的血流动力学及肾脏受累情况
Hemodynamic and renal involvement of B1 and B2 kinin receptors during the acute phase of endotoxin shock in mice.
作者信息
Seguin Th, Buleon M, Destrube M, Ranera M T, Couture R, Girolami J P, Tack I
机构信息
Laboratoire de Physiologie, Faculté de Médecine, Rangueil, Toulouse, France.
出版信息
Int Immunopharmacol. 2008 Feb;8(2):217-21. doi: 10.1016/j.intimp.2007.08.008. Epub 2007 Aug 31.
B1 kinin receptor (B1R) is up-regulated by endotoxins and thus may represent a therapeutic target in sepsis. We investigated the expression and role of B1R and B2R in the acute phase of lipopolysaccharide (LPS)-induced endotoxin shock in C57BL/6 mice (WT) and B1R and B2R knock out mice (B1KO, B2KO). B1R mRNA was enhanced from 6 to 48 h after LPS while B2R mRNA was further increased in B1KO. Maximal hypotension was found 24 h after LPS, and was more pronounced in B1KO, but was reduced in B2KO. Glomerular filtration rate was more reduced by LPS in B1KO than in WT and B2KO. Glycemia was reduced by LPS and particularly in B1KO and B2KO mice. Mortality was increased by LPS in B1KO. These data suggest that the up-regulated B1R plays, at least transiently, a significant beneficial role in acute LPS-induced hypotension. Conversely, supra activation of B2R could be also involved in the increased mortality observed in B1KO mice.
B1缓激肽受体（B1R）可被内毒素上调，因此可能是脓毒症的一个治疗靶点。我们研究了B1R和B2R在C57BL/6小鼠（野生型）以及B1R和B2R基因敲除小鼠（B1KO、B2KO）中脂多糖（LPS）诱导的内毒素休克急性期的表达及作用。LPS注射后6至48小时，B1R信使核糖核酸（mRNA）增加，而在B1KO小鼠中B2R mRNA进一步增加。LPS注射后24小时出现最大程度的低血压，且在B1KO小鼠中更明显，但在B2KO小鼠中有所减轻。与野生型和B2KO小鼠相比，LPS使B1KO小鼠的肾小球滤过率降低得更多。LPS使血糖降低，在B1KO和B2KO小鼠中尤其明显。LPS使B1KO小鼠的死亡率增加。这些数据表明，上调的B1R至少在急性LPS诱导的低血压中发挥了显著的有益作用。相反，B2R的过度激活也可能与B1KO小鼠中观察到的死亡率增加有关。
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