Leptin及其受体在非酒精性脂肪性肝炎患者肝组织中的表达

Expression of leptin and its receptors in liver tissue of nonalcoholic steatohepatitis patient

目的探讨细胞因子Leptin及其受体在非酒精性脂肪性肝炎(NASH)患者肝组织中的表达状况及其在NASH发病机制中的意义。方法应用免疫组织化学及原位分子杂交方法,对59例不同病变程度的NASH穿刺肝组织中Leptin及其受体Ob-R、Ob-Rb和Ob-Ra的表达进行检测,观察表达部位和表达量的变化,分析其与NASH病变程度之间的关系。结果NASH肝组织内,Leptin主要表达于肝腺泡3带脂变区域及纤维化明显的汇管区及其周围的库普费细胞(KC)、单个核细胞(MNC)、肝星状细胞(HSC)内;LeptinmRNA多表达于肝腺泡3带肝细胞内;Leptin受体的定位和分布与Leptin大体一致,其中Ob-Rb表达量较Ob-Ra多;Lep-tin及其受体在NASH纤维化分期(S)组和脂变分级(F)组组间的表达差异性明显(均P<0.05)。结论Leptin及其受体与NASH肝细胞脂变发生及程度密切相关,并可能作为重要的调节因子参与NASH肝纤维化过程。

Objective To explore the expression of leptin and its receptors in liver tissue of nonalcoholic steatohepatitis （NASH） patient and its significance in pathogenesis. Methyls Samples of 59 liver biopsies of NASH patients were divided into three groups G, S and F according to their degree of inflammation and steatosis and stage of fibrosis. The expression of leptin and its receptors including Oh-R, the short form of Ob-R （Ob-Ra） and the long form of Ob-R（Ob-Rb） were semi-quantitatively determined at the protein and/or rnRNA expression levels by using immunohistochemistry, in situ hybridization and image analysis. Results The expressions of leptin in NASH liver tissues were found in KC, HSC and MNC, which were mainly situated in zone 3 near steatotic hepatocytes and perisinusoidal or portal fibrosis areas. Leptin mRNA （Oh） positive cells were distributed in hepatocytes in zone 3. The expression of leptin at protein and mRNA levels in the NASH liver tissues was significantly increased in NASH compared with normal liver tissues （ P〈0. 05）, and it was parallel to the Ob-R expression level. The association of leptin up-regulated expression with steatosis grades and fibrosis stage was statistically significant （ P〈0. 05）. Ob-Ra and Ob-Rb mRNA positive cells in NASH progressively increased with the severity of liver fibrosis （ P〈0. 05）. Conclusion The results suggested that leptin and its receptors might be correlated with steatosis and play an important role in fibrogenesis and progression of NASH.