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The high mobility group protein B1 (High mobility group box 1 protein, HMGB1) 30 years ago found a nuclear non-histone proteins. Previous studies mainly focused on its role in the cell nucleus. Recent studies found that HMGB1 released by monocytes / macrophages in LPS, IL-1, TNF-α and other stimuli, also available through a variety of organizations necrotic cells escape of extracellular released into the extracellular HMGB1 can combined with multiple receptors such as RAGE, TLR4, play a biological role. All causes liver inflammation or necrosis can make HMGB1 released into the extracellular activation of TLR4 and other receptors TLR4 pathway proved to be a key node of the formation mechanism of liver fibrosis. Based on the above theory, consider HMGB1 may play an important role in the mechanism of liver fibrosis. Objective: This study begins by selecting the Bethune International Peace Hospital Shijiazhuang City Hospital patients with liver biopsy as an object of study, the detection of patients with varying degrees of liver fibrosis serum HMGB1 levels, to explore the relationship between the degree of liver fibrosis and HMGB1 levels and further by building a carbon tetrachloride model of hepatic fibrosis in mice to verify the role of HMGB1 in liver fibrosis, as well as explore the use of the the HMGB1 inhibitor of sodium butyrate prevent of HMGB1 synthesis or release can delay liver fibrosis progress, hopes for The clinical prevent liver fibrosis progression provides new strategies and approaches. Method: a collection of clinical cases: random selection from December 2008 to June 2010 age 18 to 58 years with varying degrees of chronic hepatitis B and liver cirrhosis patients with 73 cases, the diagnostic criteria in line with the Chinese Medical Association in 2005 Infectious Diseases Branch of the Chinese Medical Association Hepatology Hepatitis Prevention Foundation jointly issued by chronic hepatitis B prevention and treatment guidelines exclude other hepatitis virus infection, autoimmune hepatitis, alcoholic hepatitis, drug-induced hepatitis, cancer and other diseases as enrolled cases, including 54 cases of males, 19 females, mean age 34.6 ± 10.35 years, the G1-G 2 group of 43 patients, G3-G4 group of 30 patients, the S1-S2 group of 34 patients, the S3-S4 group of 39 cases, while select 12 healthy persons as controls, including 5 males and 7 females, mean age 33.1 ± 9.6 years, fasting blood liver function, serum HMGB1 levels detected in patients with ultrasound-guided liver biopsy pathology, to understand the degree of liver fibrosis The data analysis, a clear relationship between HMGB1 levels and liver fibrosis to understand the role of HMGB1 in the formation of liver fibrosis. 2 HMGB1 inhibitors experimental study of the prevention and treatment of liver fibrosis: clean grade male BALB / C mice 50, weighing 18 ~ 24 g, were randomly divided into the sodium butyrate prevention group 20, to give 40? L4 (olive oil dilution) , 2 mL / kg, every Tuesday, the five elements intraperitoneal injection, while giving a 1.5% sodium butyrate watering of 70 days, 20 model group given only 40? L4 (olive oil dilution) intraperitoneal injection of 2 mL / kg per On Tuesday, the five elements intraperitoneal injection, the control group (n = 10) every Tuesday and Friday to give 0.9% saline 2 mL / kg intraperitoneal injection, three groups after treatment were sacrificed 70 days, specimens of serum spare, by enzyme-linked immunosorbent assay (ELISA ) to detect HMGB1 levels, liver function, part of the liver tissue fixed in 4% paraformaldehyde for immunohistochemical examination, clear liver damage the shift of HMGB1 situation, part of the liver tissue was frozen at -80 degrees refrigerator for Western blot analysis to understand the expression of HMGB1. The result: a chronic liver disease patients HMGB1 levels and inflammatory activity relationship: HMGB1 levels in healthy control group was 16.86 ± 3.48 ng / mL, G1-G group was 26.54 ± 5.31 ng / mL, G3-G4 group was 33.64 ± 8.35 ng / mL. Patients with chronic liver disease HMGB1 levels than the healthy control group was significantly higher among the 3 groups, there were significant differences (P lt; 0.01), G3-G4 group was significantly higher than the G1-G 2 groups (P lt; 0.01). Chronic liver disease in patients with HMGB1 levels fibrosis relationship: health HMGB1 levels in the control group was 16.86 ± 3.48 ng / mL, S1-S2 group was 28.83 ± 7.53 ng / mL, S3-S4 group was 30.0 ± 7.61 ng / mL. healthy controls group S1-S2, S3-S4 group were significantly different (P lt; 0.01). S1-S2 group S3-S4 group no significant differences (P gt; 0.05). Relationship between chronic liver disease patients HMGB1 levels and liver function: serum HMGB1 levels and ALT (r = 0.2566, P lt; 0.05), AST (r = 0.4719, P lt; 0.01) showed a significant positive correlation with ALB (r = 0.114, P gt; 0.05), TBIL (r = 0.141, P gt; 0.05) no significant correlation. Sodium butyrate intervention on serum HMGB1 levels: CCl4 successful modeling serum HMGB1 levels significantly higher than the control group, the full given sodium butyrate interventions can significantly reduce serum HMGB1 levels, in which the model group 30.75 ± 7.43 ng / mL, the intervention group was 25.54 ± 3.97 ng / mL, with significant differences between groups (P lt; 0.01). 5 sodium butyrate intervention on inflammatory activity grade and fibrosis: given CCl4 modeling 70 days the mice were killed, the inflammatory activity of the model group G1-G2 level 4, G3-G4 level 10, the intervention group G1 6-G2 level 13, G3-G4 class between the two groups with a significant difference (χ2 = 5.125, P lt; 0.05). 3 fibrosis model group S1-S2, S3-S4 of 11, while the intervention group S1-S2, 12, S3-S4 7, the difference between groups (χ 2 = 5.661, P lt; 0.05 ). 6 mouse liver pathology HE and Sirius red staining: normal lobular structure was destroyed, liver cell cord disorganized, massive necrosis of liver cells, formation of visible pseudolobules; lobular architecture of the intervention group most reserved visible in the model group The visible fibers formed at regular intervals, but no typical pseudolobules formation. Mouse liver tissue immunohistochemistry: control group within the liver tissue HMGB1 expression in nuclear nucleus and the cytoplasm of a small amount of expression, no expression of cell organization. Model group is not only visible in the intracellular expression of HMGB1 in interstitial the sheet stain visible widely distributed, mostly located in the area of ??severe inflammation or presence of tissue necrosis. Compared with the model group, the intervention group organization HMGB1 expression levels were significantly lower. 8 Western blot analysis of mouse liver tissue: Compared with normal control, model group, liver tissue HMGB1 expression level was significantly higher in the intervention group HMGB1 expression levels compared with the model group decreased significantly. 9 with sodium butyrate intervention on mortality in mice: a model group of six mice died in the 70 days of the modeling process, the mortality rate was 30%, while the intervention group only one mouse died, the mortality rate 5%, with a statistically significant (P lt; 0.01). Conclusion: liver fibrosis in patients with serum HMGB1 levels compared with healthy controls was significantly higher, and is closely related to liver inflammation, may be an important reason for the start the inflammation of the liver fibrosis process. 2 mice CCL4 liver fibrosis model intrahepatic and The serum HMGB1 water on average a significant increase in liver inflammation and fibrosis were significantly positively correlated. 3 to inhibit the synthesis and release of CCL4 liver fibrosis model HMGB1 reduce the degree of inflammatory activity of the liver and liver fibrosis, slow down the progress of liver fibrosis and reduce mortality. 4 HMGB1 inhibitor sodium butyrate can significantly reduce liver fibrosis in a mouse model of intrahepatic and serum HMGB1 levels, improve histology and prognosis may be potential targets of Liver Fibrosis.
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