肝脏去唾液酸糖蛋白受体靶向活体荧光成像评估酒精性肝损伤肝脏功能的研究

In vivo fluorescence imaging of hepatocyte asialoglycoprotein receptor targeted for evaluation of liver function

目的运用肝脏去唾液酸糖蛋白受体(ASGPR)靶向活体荧光成像技术评估肝脏功能的可行性观察。方法应用小动物活体荧光成像系统分别观察正常和慢性酒精性肝损伤(cALI)小鼠尾静脉注射Cy5.5-半乳糖化多聚赖氨酸荧光探针即刻、40、60、90 min的活体荧光成像特征,并结合小鼠肝脏ASGPR的含量、血清ALT、AST、GGT水平和肝组织HE染色切片观察,分析活体荧光肝脏靶向成像特征与肝脏ASGPR表达、肝脏血清学指标及肝组织形态学特征的相关性。结果正常组小鼠肝脏区域的荧光信号强度和面积均显著高于cALI组。与正常组小鼠比较,cALI小鼠肝组织ASGPR表达显著下降。血清学检测显示cALI小鼠ALT、AST和GGT水平升高,提示肝功能损伤。形态学观察显示cALI小鼠肝组织出现肝细胞脂肪变性、炎性浸润和局灶性坏死的病理改变。结论肝脏ASGPR靶向活体荧光成像可以直观、动态、活体显示肝细胞损伤程度,可用于cALI的肝脏储备功能的评估。

Objective To analyze the feasibility of liver function evaluation using fluorescence imaging targeting to asialoglycoprotein receptor(ASGPR)in vivo.Methods The fluorescence imaging characteristics of health and chronic alcoholic liver injury(cALI)mice were observed immediately,40,60 and 90 min after injection of Cy5.5-galactosylated poly-lysine fluorescent probe into tail vein in vivo.The content of liver ASGPR,serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and gamma-glutamyl transferase(GGT),and liver tissue sections stained with HE were observed.The correlations between the features of in vivo fluorescent imaging and liver ASGPR expression,liver serological indexes and liver histomorphological characteristics were analyzed.Results The fluorescence intensity and area of liver region in the control group were significantly higher than those in the cALI group.Compared with health mice,the expression of ASGPR in liver tissue of cALI mice was significantly decreased.The levels of ALT,AST and GGT in cALI mice were elevated,suggesting liver function injury.Hepatocyte steatosis,inflammatory infiltration and focal necrosis were found in cALI mice.Conclusion In vivo liver ASGPR targeted fluorescence imaging can visually,dynamically and in vivo show the degree of hepatocyte injury,which is an experimental imaging technology that can be used to evaluate liver reserve function.