脂肪变肝细胞的CD44与炎症介质结合促进CCL2表达，通过CCR2招募M1型巨噬细胞浸润肝脏，促进非酒精型脂肪性肝炎（NASH）发生发展。参葛方是治疗NASH有效验方，改善NASH患者肝功能和影像学指标，疗效与血清CD44表达下调有关；还可抑制NASH模型鼠肝组织CD44、CCL2和CCR2表达。据此提出假说：参葛方通过抑制肝细胞CD44表达，进而下调CCL2，阻断CCR2介导的M1型巨噬细胞浸润肝脏治疗NASH。拟开展：①参葛方对NASH患者外周血和肝组织中CD44、CCL2和CCR2表达的影响；②CD44敲除和野生型小鼠构建NASH动物模型，检测肝脏M1型巨噬细胞浸润及CD44、CCL2、CCR2的表达；③肝细胞与巨噬细胞共培养，分别沉默肝细胞CD44和巨噬细胞CCR2，证实参葛方通过下调CD44-CCL2-CCR2轴抑制M1型巨噬细胞浸润肝脏，阐明参葛方治疗NASH的免疫机制。

CD44 of steatosis hepatocytes promotes the expression of CCL2 while combined with inflammatory mediators, and then recruits M1 macrophages to infiltrate the liver through CCR2 for enhancing the development of non-alcoholic steatohepatitis (NASH). Shenge Recipe is an effective prescription for treating NASH. It can make NASH patients recover from abnormal liver function and imaging indicators, and inhibits the expression of CD44, CCL2 and CCR2 in liver of NASH mice. Besides, the efficacy is related to the decrease of serum CD44. Therefore, the reaserch hypothesis is proposed that inhibiting the expression of hepatocellular CD44 can decrease CCL2 following Shenge Recipe treatment, which can block CCR2-mediated infiltration of M1 macrophages to liver. In this study, find out changes of CD44, CCL2 and CCR2 in NASH patients after taking Shenge Recipe firstly. And then, detect infiltrated M1 macrophages, as well as expression of CD44, CCL2 and CCR2 in liver of NASH model which constracted by CD44 deficient mice and wild type. Last, demonstrate Shenge Recipe supressing M1 macrophages infiltration through down-regulating CD44-CCL2-CCR2 pathway by silencing hepatocellular CD44 and CCR2 of macrophages respectively in co-culture system to further clarifying the partial immunological mechanism of therapy NASH.