Liver fibrosis is a gradual process of increased secretion and decreased degradation of extracellular materials (ECM). Most author hold that the process is initiated by the damage of hepatic cells (HCs), which leads to activation and secretion of multiple cellular factors of Kupffer cells. These factors, along with the cellular factors secreted by damaged HCs, thrombocytes and endothelial cells of the hepatic sinusoid, and some chemical mediators are activators of hepatic stellate cells (HSCs). Being activated, HSCs differentiate into myofibroblasts, and, via self-secretion and parasecretion, proliferate and synthesize a massive amount of extracellular materials which gradually accumulate and lead to formation of liver fibrosis.1 Since fibrosis is a common course in a variety of chronic liver diseases, prevention against its formation is of great importance. The following are the recent achievements of traditional Chinese medicine (TCM) in this field.

Kupffer细胞抑制剂氯化钆的研究现状

氯化钆通过抑制Kupffer细胞,可缓解肝脏疾病的发生发展.这种作用表现在多个方面:氯化钆作用于Kupffer细胞,抑制吞噬和抗原提呈,进而抑制大鼠肝移植的急性排斥反应;缺血再灌注时,保护受伤的肝脏,促进肝细胞的再生;减轻对内毒素的敏感性及内毒素所致的感染作用;有效预防和减轻酒精性肝损伤等.该文对目前氯化钆抑制Kupffer细胞,进而减轻肝脏疾病的机制的研究现状综述如下.

AIM: To determine the evolutionary pattern of parenchymal cell apoptosis in multiple organs early after intestinal ischemia-reperfusion(I/R) and its induction mechanisms and the role of apoptosis in triggering SIRS/MODS. METHODS: An I/R model was reproduced by clipping and releasing the superior mesenteric artery in rats and mice. Flow cytometry, electron microscope, DNA agarose gel electrophoresis, TUNEL method, fluorescent and Gomori's silver-HE staining were used to detect apoptosis. Distribution features of apoptotic parenchymal cells in multiple organs were observed. Immunohistochemical staining of HSP 70 and Bcl-2 were performd to study the induction mechanisms of apoptosis.RESULTS and CONCLUSION: 1. Damage of the liver, lung, gut and kidney was appeared in early phase of I/R. The percentages of apoptosis in parenchyma organs increased progressively. The percentages of cell necrosis increased with the prolonged I/R duration. 2. Percentages of apoptosis were much higher near the central veins of liver lobules, in the outer medulla of the kidney, and the antimescenteric border of intestinal mucosal epithelium because of ischemia. 3. The expression of HSP 70 increased and Bcl-2 reduced in the areas mentioned above because of hypoperfusion. 4. Apoptosis of I/R hepatocytes, splenocytes and thymocytes was obviously increased after Kupffer cell blockage with GdCl3, showing the functional state of Kupffer cells may play an important role in SIRS/MODS.

BACKGROUND: Gadolinium chloride (GdCl3) selectively in-activates Kupffer cells and protects against ischemia/reperfu-sion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplan-tation (PLTx) is not clear. This study was to investigate the role of GdCl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process.
METHODS: PLTx (30% partial liver transplantation) was per-formed using Kamada's cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose (5 mg/kg) and high-dose (10 mg/kg) GdCl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regen-eration by PCNA staining and BrdU uptake, apoptosis by TU-NEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting.
RESULTS: GdCl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine amino-transferase and aspartate aminotransferase (P>0.05). GdCl3 pretreatment induced apoptosis and inhibited IL-6 overex-pression and STAT3 phosphorylation after PLTx in graft tissues.
CONCLUSION: Kupffer cells may contribute to the liver re-generation after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway.

Objective:　To study the rule of ERK1/2 activity and regulative effect of ERK1/2 pathway on the production of pro-inflammatory cytokine TNFα in mice Kupffer cells (mKC) induced by LPS, and to exploring novel methods to prevent and treat clinical patients of endotoxemia.　　Methods:　Immunoprecipitate kinase assay and Western blotting analysis were used to detect the phosphorylated ERK1/2 kinase activity in mKC stimulated by LPS, and ELISA was used to study the effect of ERK1/2 signaling cascade on LPS-induced TNFα production in mKC.　　Results:　In mKC, LPS treatment resulted in transient and rapid increase of kinase activity of ERK1/2 that phosphorylated their specific substrate ELK-1, with maximal value at 30 minutes and a return near to baseline within 2 hours, and LPS-induced ERK1/2 activity from LPS concentration of 10 pg/ml to the top activity at 100 ng/ml. No activity was observed in unstimulated mKC. Inhibition of the ERK1/2 pathway using the specific ERK1/2 signal pathway inhibitor PD98059 caused a marked and concentration-dependent reduction of TNFα production.　　Conclusions:　The results show that LPS can markedly activate ERK1/2 pathway in mKC. PD98059 causes a significant and concentration-dependent reduction of TNFα production. ERK1/2 may be a novel target to treat clinical patient of endotoxemia.