HIV/HCV共感染者的肝纤维化进展迅速，其机制尚未完全阐明。NK细胞是肝脏内数量最多的免疫细胞，参与肝损伤的发生。本课题拟以HIV/HCV共感染、单纯HCV、单纯HIV感染者以及健康志愿者作为对照，在HIV/HCV 共感染者中采用流式细胞术、免疫组化等方法检测外周血和肝组织中NK细胞频率、分群及表面活化/抑制性受体表达、TRAIL以及相关炎症因子的表达情况。探索不同感染组NK细胞频率变化以及功能差异，研究NK细胞在HIV/HCV共感染者肝损伤加重中的作用，以及NK细胞功能差异与肝损伤程度的相关性。同时使用MiRNA芯片检测各组患者NK细胞表达MiRNA的差异，筛选出各组差异表达的MiRNA。进一步采用过表达及干涉表达的方法考察相关MiRNA在NK细胞促进HIV/HCV共感染肝纤维化快速进展中的作用及机制。从而从MiRNA-NK细胞的角度研究共感染着肝纤维化快速进展的机制。

HIV can increase the liver injury in patients of HCV infection, but the mechanism has not yet been elucidated. NK cells as the largest number of immune cells in the liver may be involved in the occurrence of liver damage.The purpose of this program is to explore the frequency and function changes of NK cells in patients of HIV/HCV co-infection compared with the patients of HCV, HIV infection and healthy volunteers. We will detect the NK cell frequency, clustering, and surface activative or inhibitory receptors and TNF related apoptosis induced ligand (TRAIL) expression in peripheral blood and liver tissue by the methods of flow cytometry, western blot, immunohistochemistry. Then study the correlation between NK cell and liver injury of HIV/HCV co-infection. MiRNAs are a novel class of small non-coding single-stranded RNAs that regulate gene expression at the posttranscriptional level by binding to target mRNAs. MiRNAs in the complex regulatory network controls both viral and host gene expression in the infected cells. MiRNA chip was used to perform a comprehensive analysis of miRNA expression from four groups. Differentially expressed miRNA lists were investigated for cognate mRNA targets in order to delineate miRNA-mRNA functional interactions. Taken together, our project will provide the first reported mechanistic data on effect of miRNA on the hepatic fibrosis mediated by NK cell and appear a strategy to slow or block hepatic fibrosis in HIV/HCV con-infected patients.