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目的通过研究NF-κBp56与人肝纤维化病理分期的相关性,探讨NF-κB在肝衰竭后肝纤维化发病机理中的作用。方法60例肝穿标本均选自2008年7月～2009年12月在我院住院的慢性乙型肝炎肝纤维化患者,其中男38例,女22例,年龄16～50岁,平均35岁,均无其他慢性疾病。所有病例均进行肝穿刺活组织检查,并进行苏木素-伊红(Hematoxylin-Eosin,HE)染色、氢氧化银氨液浸染法(Ag染)、Masson三色染色法,确定肝纤维化分期诊断(S0-S4),病理诊断标准按照2000年9月(西安)传染病与寄生虫病学分会、肝病学分会联合修订方案执行。其中S0期11例,S1期13例,S2期10例,S3期12例,S4期14例,运用免疫组化技术分别测定Ⅰ、Ⅲ型胶原、α-平滑肌肌动蛋白(alpha-smooth muscle action,α-SMA),和NF-κBp65在不同病理分期肝纤维化组织中的分布与表达,明确其相关性,并进行统计学分析。结果Ⅰ、Ⅲ型胶原的表达与肝纤维化分期(S)呈明显的正相关性,即S4>S3>S2>S1(S0),差异具有统计学意义(P<0.01);α-SMA在汇管区的表达率明显高于小叶内,并以汇管区表达为主,以出现棕黄色或棕褐色颗粒为阳性,肝纤维化程度重时,在汇管区、纤维间隔,特别是汇管区边缘碎屑样坏死处有较强的阳性信号,与肝纤维化分期(S)呈明显的正相关性,即S4>S3>S2>S1(S0),差异具有统计学意义(P<0.01);NF-κBp65的阳性染色部位位于肝细胞浆及细胞核,以细胞核内为多,肝纤维化程度重时则有较强的阳性信号,与肝纤维化分期(S)呈明显的正相关性,即S4>S3>S2>S1(S0),差异具有统计学意义(P<0.01);NF-κBp65与α-SMA、Ⅰ型胶原、Ⅲ型胶原的表达呈正相关性。结论 NF-κBp65的表达与肝衰竭后肝纤维化的发生发展有关。其机制可能与促进肝星状细胞活化后表达α-SMA增加,Ⅰ型胶原和Ⅲ型胶原分泌增加有关。
Objective To investigate the role of NF-κB in the pathogenesis of hepatic fibrosis after liver failure by studying the relationship between NF-κB p56 and pathological stage of human liver fibrosis. Methods Totally 60 cases of liver biopsy specimens were selected from patients with chronic hepatitis B liver fibrosis hospitalized in our hospital from July 2008 to December 2009, including 38 males and 22 females, aged from 16 to 50 years, with an average of 35 years , No other chronic diseases. Liver biopsy was performed in all the cases, Hematoxylin-Eosin (HE), Ag staining and Masson trichrome staining were performed to confirm the staging of liver fibrosis S0-S4), pathological diagnostic criteria in accordance with the September 2000 (Xi’an) Epidemiology and Parasitology Branch, Liver Branch will jointly implement the revised program. There were 11 cases in stage S0, 13 cases in stage S1, 10 cases in stage S2, 12 cases in stage S3 and 14 cases in stage S4. Immunohistochemistry was used to detect the expressions of collagen type I and III, alpha-smooth muscle action, α-SMA), and NF-κBp65 in different pathological stages of liver fibrosis tissue distribution and clear correlation, and statistical analysis. Results The expression of type Ⅰ and type Ⅲ collagen was positively correlated with the stage of liver fibrosis (S), ie, S4> S3> S2> S1 (S0), the difference was statistically significant (P <0.01) The expression rate in portal area was significantly higher than that in lobular area, and was mainly expressed in portal area, with the appearance of brownish-yellow or brown granules. When the degree of hepatic fibrosis was heavy, in portal area, fiber space, especially the edge of portal area There was a significant positive correlation between the debris-like necrosis and the stage of liver fibrosis (S), ie, S4> S3> S2> S1 (S0), the difference was statistically significant (P <0.01) The positive staining sites of -κBp65 were located in the cytoplasm and nucleus of hepatocytes, with more nuclei and more positive signals when the degree of hepatic fibrosis was severe, which was positively correlated with the stage of liver fibrosis (S) (P <0.01). There was a positive correlation between NF-κBp65 and the expression of α-SMA, collagen type Ⅰ and collagen type Ⅲ. Conclusion The expression of NF-κBp65 is related to the occurrence and development of hepatic fibrosis after liver failure. The mechanism may be related to the enhancement of α-SMA expression and the increase of type Ⅰ collagen and type Ⅲ collagen after hepatic stellate cells activation.