乳凝集素抗独特型抗体Ab2β在人轮状病毒腹泻乳鼠模型治疗中的作用  

Role of lactadherin anti-idiotypic monoclonal antibodies Ab2βin the treatment of human rotavirus-induced diarrhea in a neonatal mouse model

作　　者：孙丽[1] 张诗海 胡芳芳 SUN Li;ZHANG Shihai;HU Fangfang(Department of Clinical Laboratory,Hefei Third People's Hospital,Hefei,Anhui 230002,China;Department of Clinical Laboratory,Anhui Children's Hospital,Hefei,Anhui 230001,China)

机构地区：[1]合肥市第三人民医院检验科,安徽合肥230002 [2]安徽省儿童医院检验科,安徽合肥230001

出　　处：《中国热带医学》2023年第7期736-741,共6页China Tropical Medicine

基　　金：合肥市卫计委应用医学研究项目(No.hwk2016zc010)。

摘　　要：目的 探讨乳凝集素抗独特型抗体Ab2β在新生乳鼠感染人轮状病毒(human rotavirus, HRV)的预防与治疗中的作用,并分析其作用机制。方法 采用杂交瘤技术制备乳凝集素抗独特型抗体;选取120只7日龄昆明小鼠乳鼠作为研究对象,采用随机数字表法将其分为A、B、C组以及对照组,每组30只,A、B、C三组均采用灌胃病毒方式造模,其中A组造模后不进行任何处理,B组在造模前连续7 d喂服乳凝集素,C组在造模后连续7 d喂服乳凝集素,对照组灌胃不含病毒的细胞培养液。观察各组乳鼠感染病毒后不同时间点的临床表现(腹泻、体重)并采用酶联免疫分析法(enzyme-linked immunosorbent assay, ELISA)检测乳鼠粪便中轮状病毒抗原含量;HRV感染7 d后,采用免疫组化法检测各组乳鼠小肠组织细胞间粘附分子1(intercellular adhesion molecule-1, ICAM-1)的表达水平。结果 对照组新生乳鼠各时间点均未非发生腹泻,A、B、C 3组乳鼠在HRV攻击1 d后出现腹泻症状,B、C组腹泻程度在HRV攻击后2~4 d低于A组,差异有统计学意义(P<0.05);B、C组乳鼠粪便中HRV抗原含量在HRV攻击后1~5 d低于A组,差异有统计学意义(P<0.05),B、C组各时间点腹泻程度和HRV抗原含量比较,差异均无统计学意义(P>0.05)。各组乳鼠感染前、感染后1 d体重比较,差异无统计学意义(P>0.05);B、C组乳鼠在HRV攻击后3、5、7 d体重高于A组,差异有统计学意义(P<0.05),B、C组乳鼠在HRV攻击后各时间点体重比较,差异均无统计学意义(P>0.05)。A、B、C三组乳鼠在HRV攻击7 d后小肠组织ICAM-1表达细胞数高于对照组,差异有统计学意义(P<0.05),B、C组ICAM-1表达细胞数及灰度值低于A组,差异有统计学意义(P<0.05)。结论 乳凝集素抗独特型抗体Ab2β对新生乳鼠人轮状病毒感染具有很好的预防与治疗作用,可显著改善腹泻症状、降低HRV病毒载量,其具体作用机制可能与抑制小肠组织ICAM-1的表达有关。Objective To investigate the preventive and therapeutic effects of anti-idiotypic monoclonal antibodies(Ab2β)of lactadherin on neonatal mice infected with human rotavirus(HRV),and to analyze the underlying mechanism.Methods Hybridoma technology was used to prepare Ab2βof lactadherin.One hundred and twenty 7-day-old Kunming mice were randomly divided into groups A,B,C and control,each consisting of 30 mice.Groups A,B,and C were all infected with HRV via oral gavage.Group A received no treatment,group B was orally administered lactadherin for 7 days prior to infection,and group C was orally administered lactadherin for 7 days after infection,the control group was orally administered cell culture medium that did not contain the virus.The clinical manifestations(diarrhea,body weight)at different time points after infection of the neonatal mice in each group were observed,and the content of rotavirus antigen in the feces of neonatal mice was detected by enzyme-linked immunosorbent assay(ELISA).After HRV infection for 7 days,immunohistochemical staining was used to examine the expression level of intercellular adhesion molecule-1(ICAM-1)in mouse small intestinal tissues in each group.Results No diarrhea occurred in the control group at any time point.Groups A,B,and C showed diarrhea symptoms after HRV challenge for 1 day.The degree of diarrhea in groups B and C was lower than that in group A at 2-4 days after HRV challenge,and the difference was statistically significant(P<0.05).The HRV antigen content in the feces of the neonatal mice in groups B and C was lower than that in group A at 1-5 days after HRV challenge,and the difference was statistically significant(P<0.05).There was no significant difference in the degree of diarrhea and HRV antigen content between groups B and C at each time point(P>0.05).There was no significant difference in the body weight of the neonatal mice in each group before infection and 1 day after infection(P>0.05);the weight of neonatal mice in groups B and C was higher than that in group

关 键 词：乳凝集素抗独特型抗体Ab2β 人轮状病毒 腹泻 白细胞黏附分子 

分 类 号：R373[医药卫生—病原生物学]