Role of macrophage scavenger receptor A in the progression of dietary steatohepatitis in mice

雄性MSR-A敲除（MSR-A^<-/->）小鼠和年龄匹配的C57Bl/6J （MSR-A^<+/+>）小鼠分别饲喂MCD日粮或鼠粮5周或15周。组织染色法测定炎症和纤维化程度。分别用定量逆转录- pcr （RT-PCR）检测基因表达。通过组织病理学和F4/80的免疫组化结果显示，MSR-A缺乏减轻了MCD喂养小鼠的坏死炎症反应和巨噬细胞积聚。这种情况降低了肝脏促炎基因如肿瘤坏死因子- α、单核细胞趋化蛋白1、巨噬细胞集落刺激因子和促纤维化基因如I型胶原α 1、III型胶原α 1、α-平滑肌肌动蛋白、金属蛋白酶-2组织抑制剂、结缔组织生长因子的表达。此外，MSR-A缺乏显著减少肝脏中的胶原沉积。这些结果表明，MSR-A参与了脂肪性肝炎小鼠模型肝脏炎症和纤维化的增强。

Male MSR-A knockout (MSR-A^<-/->) mice and age-matched C57Bl/6J (MSR-A^<+/+>) mice were fed either MCD diet or chow diet for 5 or 15 weeks. Inflammation and fibrosis were determined by tissue staining. Gene expressions were determined by quantitative reverse transcription-PCR (RT-PCR), respectively. MSR-A deficiency attenuated necroinflammatory reaction and macrophage accumulation, as indicated by histopathology and immunohistochemistry for F4/80, in mice fed the MCD diet. This condition reduced the hepatic expression of the proinflammatory genes, such as tumor necrosis factor-alpha, monocyte chemotactic protein 1, and macrophage colony stimulating factor and the profibrogenic genes, such as collagen type I alpha 1, collagen type III alpha 1,α-smooth muscle actin, tissue inhibitor of metalloproteinase-2, and connective tissue growth factor. In addition, MSR-A deficiency significantly reduced collagen deposition in the livers. These results indicate that MSR-A contributes to the augmentation of hepatic inflammation and fibrosis in the mouse model of steatohepatitis.