Higuchi Nobito, Kato Masaki, Kotoh Kazuhiro, Kohjima Motoyuki, Aishima Shinichi, Nakamuta Makoto, Fukui Yoshinori, Takayanagi Ryoichi, Enjoji Munechika
Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Higashi-ku, Fukuoka, Japan.
Liver Int. 2007 Dec;27(10):1342-8. doi: 10.1111/j.1478-3231.2007.01590.x. Epub 2007 Sep 26.
We have reported that hepatic arterial steroid injection is an effective therapy to rescue patients from fulminant or severe acute hepatic failure. We speculate that a high concentration of steroid suppresses inflammatory processes in the liver directly by restraining activated inflammatory cells, including macrophages. To analyse the detailed mechanism, steroid injection via the portal vein was performed in an experimental model of liver damage.
Rats subjected to lipopolysaccharide and d-galactosamine injection were treated with a methylprednisolone injection via the tail vein or the portal vein. The survival rate, serum levels of inflammatory cytokines and apoptotic cell counts in the liver were analysed.
The survival rate was significantly improved by steroid injection, especially via the portal vein. Serum values of alanine aminotransferase, tumor necrosis factor-alpha and interferon-gamma were reduced in the treated groups, especially the group given portal venous injections. Apoptotic cell counts in the liver were significantly lower in the group injected with steroid via the portal vein.
In the model rats, high concentrations of steroid in the liver acted on inflammatory cells and suppressed inflammatory cytokines and liver cell death. The mechanism is suggested to be the same for arterial steroid injection therapy in patients with acute hepatic failure.
我们曾报道肝动脉注射类固醇是一种有效的治疗方法,可挽救暴发性或严重急性肝衰竭患者。我们推测高浓度的类固醇通过抑制包括巨噬细胞在内的活化炎症细胞,直接抑制肝脏中的炎症过程。为分析详细机制,在肝损伤实验模型中进行了门静脉注射类固醇。
对接受脂多糖和d-半乳糖胺注射的大鼠,通过尾静脉或门静脉注射甲基泼尼松龙进行治疗。分析存活率、血清炎症细胞因子水平及肝脏中的凋亡细胞计数。
注射类固醇,尤其是通过门静脉注射,可显著提高存活率。治疗组中丙氨酸转氨酶、肿瘤坏死因子-α和干扰素-γ的血清值降低,尤其是门静脉注射组。通过门静脉注射类固醇的组中肝脏的凋亡细胞计数显著更低。
在模型大鼠中,肝脏中的高浓度类固醇作用于炎症细胞,抑制炎症细胞因子和肝细胞死亡。急性肝衰竭患者动脉注射类固醇治疗的机制可能与此相同。