Aspect of Strategy for Liver Failure by Regelating Hepatic Stellate Cell Activation

(1)IV型胶原在慢性肝损伤患者肝脏手术中的意义：在有和没有慢性肝损伤的患者围手术期测量IV型胶原（IV-Col）。在肝硬化患者中显著升高。肝硬化患者术后血清IV-Col水平明显高于正常肝组织和慢性肝炎患者。在术前血清IV-Col水平为150>、150 - 300和> 300 ng/ml的病例中，术后肝功能衰竭的发生率分别为0%、11.6%和44.4%。在术后肝功能衰竭的情况下，血清IV-Col水平显着高于术前和术后相比，那些顺利的情况下。IV-Col是术后肝功能衰竭的独立危险因素。(2)NAC（N-乙酰半胱氨酸）抑制肝星状细胞增殖和肝纤维化：NAC剂量依赖性地阻断PDGF诱导的DNA合成和信号转导，包括DNA合成和信号转导。 ...更多信息 原代培养肝星状细胞，应用MAPK和Akt。在体外降解实验中，不同的蛋白酶抑制剂显示，还原剂，包括NAC，增强组织蛋白酶B的催化活性，并触发细胞外的PDGFR的蛋白水解，从而导致细胞对PDGF-BB的脱敏。Western blot结果显示肝星状细胞分泌成熟的组织蛋白酶B，而血管平滑肌细胞不分泌组织蛋白酶B。这种机制在体内肝纤维化模型中得到证实。(3)肝星状细胞对肝细胞增殖的调节1.应用共培养模型研究了星状细胞（HSC）对肝细胞增殖的影响。当与HSC共培养时，肝细胞DNA合成增强。HSC产生的HGF可能是促进肝细胞增殖的主要因素。细胞外基质可增强HGF的作用。HSC与肝细胞接触可减弱肝细胞的增殖，其中缝隙连接可能也参与了肝细胞增殖的调节。少

(1) SIGNIFICANCE OF TYPE IV COLLAGEN IN LIVER SURGERY FOR PATIENTS WITH CHRONIC LIVER INJURY: Type IV collagen (IV-Col) was measured perioperatively in patients with and without chronic liver damage. It was significantly elevated in cases with liver cirrhosis. In patients with liver cirrhosis, the postoperative serum IV-Col level significantly increased as compared to cases with normal liver and chronic hepatitis. Postoperative liver failure occurred at 0%, 11.6%, and 44.4% in cases with preoperative serum IV-Col levels of 150>, 150-300, and >300 ng/ml, respectively. In cases with postoperative liver failure, serum IV-Col levels were significantly higher both pre-and postoperatively as compared to those of uneventful cases. IV-Col revealed to be an independent risk factor for postoperative liver failure.(2) NAC (N-ACETYL CYSTEINE) SUPPRESSED PROLIFERATION OF HEPATIC STELLATE CELL AND LIVER FIBROSIS: NAC dose-dependently blocked PDGF-induced DNA synthesis and signal transduction, includ … More ing MAPK and Akt, inprimary-cultured hepatic stellate cell. In vitro degradation assay with various protease inhibitors showed that reducing agents, including NAC, enhanced the catalytical activity of cathepsin B and triggered extracellular proteolysis of PDGFR, thereby leading to desensitization of the cell to PDGF-BB. Moreover, western blot showed that hepatic stellate cell secreted mature-cathepsin B into the culture medium, while vascular smooth muscle cell did not secrete cathepsin B. This nechanism was demonstrated in in vivo liver fibrosis models.(3) HEPATIC STELLATE CELLS REGULATE PROLIFERATION OF HEPATOCYTES lEffect of stellate cells (HSC) on proliferation of hepatocytes was investigated using co-culture models. When co-cultured with HSC, hepatocyte DNA synthesis was enhanced. HGF produced by HSC seemed to be the primary factor to enhance hepatocyte proliferation. The action of HGF was augmented by extracellular matrix. The contact of HSC with hepatocyte attenuated the enhanced proliferation of hepatocyte, in which gap junction seemed also to regulate proliferation of hepatocyte. Less