胃旁路手术通过改善肝脂肪变的危险因素，可逆转非酒精性脂肪性肝炎（nonalcoholic steatohepatitis, NASH）。但因存在手术损伤，难以用于NASH防治。近期发现，这一"肝-肠对话"机制主要基于促NASH的抑胃肽（gastric inhibitory polypeptide, GIP）下调，以及抑制NASH的胰高血糖素样肽 (glucagons-like peptides，GLPs) 表达增高。为此，本研究拟由下消化道L细胞中克隆GLPs的开放读码框序列，分别构建GIP启动子驱动的重组慢病毒，并靶向导入上消化道的GIP分泌细胞-K细胞。以期借助正常饮食在胃肠道全程刺激GLPs的分泌，并通过提高GLPs/GIP比例抑制GIP功能，从而在生理条件下重塑"肝-肠对话"模式，实现对NASH的干预作用。

Gastrointestinal bypass is proved to ameliorate the risk factors of hepatic steatosis, and then reverses the nonalcoholic steatohepatitis (NASH). But the operative injury prevents it from the prevention and treatment of NASH. Recently, the therapeutic mechanisms underlying gastrointestinal bypass have been attributed to the down-regulation of gastric inhibitory polypeptide (GIP), a NASH-inducing hormone, and up-regulation of glucagons-like peptides (GLPs), which share the characteristics of NASH inhibition. We, therefore, attempt to clone the GLPs ORF sequences from L cell in lower digest tract, and construct the recombinant lentivirus driven by GIP promoter. After K-cell targeted GLPs accommodation, GLPs secretion may be stimulated in the whole digest tract by normal meal. The altered GLPs/GIP ratio also inhibits the function of GIP. In result, effective therapy of NASH could be induced on the basis of 'liver-gut cross talk' remodeling.