1969年Gall等首先将分子杂交技术应用于细胞和染色体的研究,1978年Brahic和Hasse改进了探针标记技术和原位杂交方法,并应用于检测细胞内的病毒基因。1981年Gowans应用该技术检测HBV感染的肝细胞内的HBV DNA,这对于在原位了解肝细胞内乙肝病毒基因及该基因的表达和肝炎病变关系 In 1969, Gall et al first applied molecular hybridization to the study of cells and chromosomes. In 1978, Brahic and Hasse improved the technique of probe labeling and in situ hybridization and applied it to the detection of intracellular viral genes. In 1981, Gowans applied this technique to detect HBV DNA in HBV-infected hepatocytes, which is of great significance for understanding the relationship between hepatitis B virus gene and the expression of hepatitis B virus gene and hepatitis in situ in hepatocytes