日本血吸虫可溶性成虫抗原和可溶性虫卵抗原对小鼠1型糖尿病的拮抗作用研究

Study of antagonistic effect of SWA and SEA of Schistosoma japonicumin mice with type 1 diabetes

目的探讨日本血吸虫可溶性成虫抗原(SWA)和可溶性虫卵抗原(SEA)对小鼠1型糖尿病的拮抗作用。方法把24只成功建模的1型糖尿病小鼠随机分3组(A、B、C组),每组8只小鼠。同时制备日本血吸虫SWA和SEA。A组模型鼠经腹部皮下多点注射日本血吸虫SWA进行免疫;B组模型鼠经腹部皮下多点注射日本血吸虫SEA进行免疫;C组模型鼠用PBS代替抗原腹部皮下免疫,1周免疫1次,共4次,4周后,颈椎脱臼处死各组小鼠,留取血清,采用ELISA双抗夹心法测定各组小鼠血清中IL-4和IFN-γ的水平,并取胰腺观察病理改变。结果免疫4周后,B组小鼠血清IL-4水平[(23.87±4.85)pg/mL]高于C组[(4.39±0.56)pg/mL],差异有统计学意义(P<0.01),而IFN-γ水平[(271.85±26.04)pg/mL]低于C组[(362.79±32.50)pg/mL],差异也具有统计学意义(P<0.01)。但是A组小鼠IL-4水平[(5.09±0.37)pg/mL]和IFN-γ水平[(379.56±34.47)pg/mL],与C组比较,差异无统计学意义(P>0.05)。B组小鼠的胰岛结构虽没有保持完整,但淋巴细胞浸润较C组少,胰岛内部也未见大量淋巴细胞浸润。与C组小鼠胰腺相比,A组小鼠胰腺未见明显变化,胰岛仍可见大量淋巴细胞浸润,残余胰岛细胞数量减少,并可见少数胰岛结构被破坏。结论日本血吸虫SEA对糖尿病1型小鼠具有一定拮抗作用,其作用机制可能是通过使IL-4升高和IFN-γ下降,调节Th1/Th2免疫偏移,导致Th1反应下调,Th2反应增强。

Objective To explore the antagonistic effect of Schistosoma japonicum soluble adult worm antigen （SWA）and solu-ble egg antigen （SEA）in the mice with type 1 diabetes.Methods The 24 successful modeling type 1 diabetes mice were randomly divided into three groups （A,B,C group,n=8）.SWA and SEA of Schistosoma japonicum were prepared.Mice in A group were immunized by abdominal subcutaneous multi-point injection SWA.Mice in B group were immunized by abdominal subcutaneous multi-point injection SEA.And mice models of C group were immunized by PBS instead of antigen through abdominal subcutaneous injection.The mice got immunization once a week,a total of four times.4 weeks later,the mice were sacrificed,and serum specimens were collected for the determination of serum levels of IL-4 and IFN-γby double-antibody sandwich ELISA,while pancreas tissues were collected and the pathological changes were observed.Results The serum IL-4 level of B group [（23.87 ±4.85）pg/mL]was higher than C group [（4.39 ± 0.56 ）pg/mL],with significant differences （P 〈 0.01 ）,while the serum IFN-γ level [（271.85±26.04）pg/mL]was lower than C group [（362.79 ±32.50）pg/mL],also with significant differences （P 〈0.01）.The serum IL-4 and IFN-γof A group were （5.09±0.37）pg/mL and （379.56±34.47）pg/mL,which had no difference with C group （P〉0.05）.The islet structure of mice in B group was not intact,however,the lymphocytic infiltration in B group was less than C group,and there was no lymphocytic infiltration in pancreatic islets in B group.Compared with C group,the pancreas of mice in A group did not have significant changes,lymphocytes infiltration was still visible in islets.The number of residual islet cells de-creased,and visible minority islet structure was destroyed.Conclusion SEA of Schistosoma japonicum has certain antagonism effect on type 1 diabetes in experimental mice.Its mechanism may be the reduction of Th1 response and the enhancement of Th2 response through increasing IL-4 level and decreasing IFN-γlevel.