Nielsen Susanne Schouw, Grøfte Thorbjørn, Tygstrup Niels, Vilstrup Hendrik
Department of Medicine V (Hepatology & Gastroenterology), Aarhus University Hospital, Noerrebrogade 44, DK-8000 Aarhus C, Denmark.
Comp Hepatol. 2006 Sep 12;5:3. doi: 10.1186/1476-5926-5-3.
In patients with cirrhosis, infection is frequent and a leading cause of death. This is secondary to various immunologic abnormalities in both the innate and the adaptive immune system. However, it remains unclear whether cirrhosis affects the inflammatory systemic component of the innate immunity, 'the acute phase response', mostly effectuated by the liver itself. We hypothesized that rats with cirrhosis raise a reduced acute phase response induced by lipopolysaccharide (LPS).
We examined the acute phase response induced by intraperitoneal injection of a low dose of LPS, in sham operated control animals and in rats with liver cirrhosis induced by bile duct ligation (BDL). We measured the serum concentrations of the most important acute phase proteins and their liver tissue gene expressions, assessed by mRNA levels. The BDL-model itself increased the serum concentration of alpha1-acid glycoprotein (alpha1AGP) and haptoglobin. LPS was lethal to 25% of the cirrhotic animals and to none of the controls. Twenty-four hours after LPS, the serum concentration of alpha1AGP and haptoglobin, the mRNA level of these acute phase proteins and of alpha2-macroglobulin and thiostatin rose to the same level in the animals with cirrhosis and in controls.
In rats with experimental cirrhosis LPS caused high mortality. In the survivors, the cirrhotic liver still synthesized acute phase proteins as the normal liver, indicating a normal hepatic contribution to this part of the acute phase response.
在肝硬化患者中，感染很常见且是主要死因。这继发于先天性和适应性免疫系统的各种免疫异常。然而，肝硬化是否影响先天性免疫的炎症全身性成分“急性期反应”（主要由肝脏自身完成）仍不清楚。我们推测肝硬化大鼠对脂多糖（LPS）诱导的急性期反应减弱。
我们检测了假手术对照动物和胆管结扎（BDL）诱导的肝硬化大鼠腹腔注射低剂量LPS后引发的急性期反应。我们测量了最重要的急性期蛋白的血清浓度及其肝脏组织基因表达（通过mRNA水平评估）。BDL模型本身增加了α1-酸性糖蛋白（α1AGP）和触珠蛋白的血清浓度。LPS对25%的肝硬化动物致死，对所有对照动物均无致死作用。LPS注射24小时后，肝硬化动物和对照动物中α1AGP和触珠蛋白的血清浓度、这些急性期蛋白以及α2-巨球蛋白和硫抑素的mRNA水平均上升至相同水平。
在实验性肝硬化大鼠中，LPS导致高死亡率。在存活者中，肝硬化肝脏仍能像正常肝脏一样合成急性期蛋白，表明肝脏对急性期反应的这一部分贡献正常。
