Abstract:

Objective To investigate the effects of adult-worm excretory-secretory protein (AES) and the excretory-secretory antigen of eggs (ESA) of Schistosoma japonicum on the mice with type Ⅰ diabetes, and preliminarily explore the mechanisms of the antigens in the mice. Methods Twenty-four male KM mice were randomized to groups of blank control, PBS, AES and ESA (n= 6 in each group). Mice in the blank control were free of any intervention, whereas those in PBS, AES and ESA groups were injected with streptozotocin (STZ) solution to prepare type Ⅰ diabetes model. After successful modeling, the mice were immunized subcutaneously with PBS, AES or ESA, respectively, at multiple points in the abdomen, once a week, for 4 consecutive weeks. The blood glucose of mice was detected 1 week after immunization intervention and continued for 4 weeks. After 4 weeks of immune intervention, the serum levels of IL-4 and IFN-γ were measured by ELISA, and the pathological changes of pancreatic tissue were detected by HE staining. Results Compared with the PBS group, the blood glucose levels of mice in the AES and ESA groups showed a decreasing trend from the 2^nd week after immunization, and the blood glucose levels of mice in the ESA group were lower than those in the AES group. The difference in blood glucose levels was significant between the groups at the 2^nd, 3^rd and 4^th weeks after immunization (F=1 214.00, 1 055.00, 683.64, all P<0.05), and the serum IL-4 and IFN-γ levels were significantly different between groups (F=146.84, 21.11, both P<0.05). The serum IL-4 level in ESA group [(61.45±6.14) pg/mL] was higher than that in PBS group [(21.96±3.98) pg/mL] and AES group [(49.31±3.19) pg/mL], yet the IFN-γ level [(129.48±36.75) pg/mL] was lower than that in PBS group [(316.43±66.38) pg/mL] and AES group [(212.09±70.89) pg/mL], with statistical difference (all P<0.05). Pancreatic islet atrophy, decrease in number and vacuole-like degeneration were observed in mice in PBS group, whereas pancreatic islet atrophy appeared slight in mice in ESA group, and the severity of pathological changes in the pancreatic tissues was moderate between PBS and ESA group. Conclusion The ESA of Schistosoma japonicum has a certain protective effect on mice with type Ⅰ diabetes. The mechanism may be that after ESA stimulation, Th1 response is inhibited, while Th2 response is enhanced, which is manifested by the increase of IL-4 and the decrease of IFN-γ, eventually alleviating the pathological damage to pancreatic tissues to a certain extent.

Key words: Schistosoma japonicum, Adult-worm excretory-secretory protein, Excretory-secretory antigen of eggs, Type Ⅰ diabetes mellitus