Study On The Protective Effect And Mechanisms Of The ω-3 Polyunsaturated Fatty Acids To The Schistosomiasis Liver Fibrosis In Mice

Objectives:Observing the effect of theω-3 polyunsaturated fatty acids on the starting and resolving of the schistosomiasis inflammatory response and liver fibrosis , the serum level of signal of liver fibrosis, the living states and function of liver cells ,to investigate the protective effect and mechanisms of theω-3 polyunsaturated fatty acids to the liver fibrosis induced by Schistosoma japonicum infection in mice, so provide the theoretical basis and strategy for its new clinic treatment method.Methods:The mice infected with the cercariae of Schistosoma japonicum (20±cercarie per mice via abdominal respectively)were separated randomly into three groups: Schistosoma japonicum model group(group A,10 mice), praziquantel treatment group (group B, 10 mice),ω-3 polyunsaturated fatty acids and praziquantel combined treatment group(group C,30 mice).Then, the group C were randomly divided into 3 equal groups: group C₁ was treated before the soluble eggs antigen (SEA) released into blood, that is 12 days after infected with cercariae; group C₂ and C₃ were treated after the SEA released into blood, that are respectively 35 days and 42 days after infected with cercariae.At the three different time ,mice of group C were combined treatment withω-3 polyunsaturated fatty acids and praziquantel (ω-3 polyunsaturated fatty acids 2ml/kg per mouse per day,Vi×7days, praziquantel 500mg/kg per mouse per day, gavage×2days).And group B was treated with praziquantel(500mg/kg per mouse per day, gavage×2days). At the same time,10 else uninfected mice were chosen as control group(group D).After 60 days, liver tissue samples of all mice were sectioned and stained with HE and Masson to measure the size of egg(ovum) granoma and assess the collagen deposited in mice's livers. And the serum level of hyaluronic acid(HA) and laminin(LN) were evaluated by radioimmunossay(RIA). Immunohistochemistry forα-smooth muscle actin(α-SMA) as an activated hepatic stellate cell(HSC) marker was performed to detect and quantify activated HSC by SP technique. The serum level of interferon-γ(IFN-γ),interleukin-13(IL-13) and tumor necrosis factor-α(TNF-α)were tested by enzyme-link edimmunosorbentassay (ELISA). The proliferation degree of CD4⁺T cell and CD8⁺T cell was evaluated by flow cytometry(FCM).Rests:Observed through HE and Masson staining, the size of egg(ovum) granoma and the collagen deposited in mice's livers in group C₁ were less than that of group A and group B. The serum level of IL-13 and TNF-α(0.27±0.02pg/μl,71.08±6.21pg/μl)were lower than that of group A(0.67±0.04pg/μl,129.77±8.34pg/μl)and group B(0.38±0.03pg/μl, 90.41±5.51pg/μl), when IFN-γhigher than that of group A and group B(0.54±0.03pg/ml VS0.17±0.02pg/ml, 0.42±0.02pg/ml)(P<0.01). The indicators of liver fibrosis, such as HA and LN in group C₁(822.35±69.62ng/ml,1233.07±42.69ng/ml) were lower than that of group A(1735.85±141.49ng/ml,1871.83±52.96ng/ml) and group B(1061.96±144.68ng/ml,1400.74±32.24ng/ml) (P<0.01). Compared with group A and group B, theα-SMA expression of the C₁ group decreased significantly. The percentage of the CD4 + T cell in C₁ group was lower than the normal group (group D), there was the statistically significant in the two groups (P < 0.05). while compared with C₁ group and infection model group (group A), praziquantel treatment group(group B) , The percentages of the CD4 + T cell were no significantly difference in the three groups.All groups had no significant difference with the proliferation degree of CD8⁺T cell .The C₂ group and C₃ group compared with B, all the testing indexes were no obvious difference.Conclusions:Before the soluble eggs antigens was release into the blood, the dosing method ofω-3 polyunsaturated fatty acids and praziquantel combined treatment could obviously decrease liver ovum granomatous inflammation and fibrosis degree in the schistosomiasis , the mechanism of the omega - 3 polyunsaturated fatty acid was relevant its effects of the anti-inflammatory and immune adjustment.