ABSTRACT
Objective To establish the lipopolysaccharide(LPS)-induced autism spectrum disorder(ASD) models at second trimester in rat offspring,and to investigate the effect of LPS exposure on social interaction behavior and neuro-immune system in rat offspring.Methods Twelve-week-old pregnant specific pathogen free rats were randomly divided into non-exposed group(10 cases) and LPS-exposed group(10 cases).Rats in the exposure group were intraperitoneally injected with LPS 25 mg/kg at 12.5 d,while rats in the non-exposed group were intraperitoneally injected with 9 g/L saline.At the age of 28 days,10 rats were randomly selected from each group as the experimental group and the control group.The following tests were carried out in two groups of rats.Their offspring were randomly allocated to the control group (10 cases) and the experimental group (10 cases).The autism-like social behaviors were evaluated by the social interaction test.Density of dendritic spine was analyzed by Golgi staining.The expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA1) were analyzed by immunohistochemisty.The levels of i nterleukin (IL)-1 β,IL-4,IL-6,IL-10,interferon-gamma (IFN-γ'),and transforming growth factor-beta(TGF-β) in rat offspring were detected by enzyme-linked immunosorbent assay.Results The score of social interaction test in the experimental group [(-197.81 ± 101.83) scores] was lower than that in the control group [(132.73 ± 114.63) scores],and the difference was statistically significant (t =5.453,P ＜ 0.05).Density of dendritic spine in CA1 region of hippocampus was lower in the experimental group[(7.71 ± 1.33) numbers/10 μm] than that in the control group[(9.66 ± 1.76) numbers/10 μm] by Golgi staining,and the difference was statistically significant(t =2.775,P ＜ 0.05).Expressions of GFAP and IBA1 in experimental group were higher than those in the control group by immunohistochemisty.Levels of IL-1 β,IL-6,IL-10 and IFN-γ in the experimental group were higher than those in the control group,while level of TGF-β was lower than that in the control group,and the differences were statistically significant(all P ＜0.05).The scores of social interaction test were correlated with the levels of IFN-γ(r =0.756,P ＜ 0.05).Conclusion LPS exposure at early pregnancy may affect the neuro-immune system of rat offspring and result in autism-like behavior.
ABSTRACT
Objective To investigate the role and significance of E selectin in the pathogenesis of neonatal acute lung injury (ALI).Method Ninety neonatal Sprague Dawley (SD) rats (6 or 7 days after birth) were randomly assigned to the control group (n =10) and ALI group (n =80).The rats in the ALI group received intraperitoneal injection of lipopolysaccharide (LPS) at dose of 4 mg/kg and they were divided into eight subgroups with 10 rats in each group according to different sacrifice time (0.5 h,1 h,2 h,3 h,4 h,8 h,12 h and 24 h after injection).Rats in the control group were injected intraperitoneally the same volume of normal saline and they were sacrificed at 4 hours after injection.Expression of the E-selectin in lung tissue was detected dynamically by immunohistochemistry and the serum soluble endothelial selectin (sE-selection) was detected by enzyme-linked immunosorbent assay (ELISA).The pathological changes of the lung tissue and the wet/dry lung weight ratio (W/D ratio) were recorded.Result The strong expression of a large number of E-selectin was detected in the vascular endothelial cells of the lung tissue in the ALI group,while only moderate expression of E-selection was observed in the control group.The W/D ratio in the ALI group gradually increased from 0.5 h after intraperitoneal injection of LPS,reached the peak at 8 h,and then began to decline.The ratio was significantly higher in the ALI group than that of the control group from 4 to 12 h after injection (P ＜ 0.05).The mean optical density of E-selectin in lung tissue of ALI group was also higher than that of the control group and the average optical density of ALI group at 2 h,3 h,4 h and 8 h was significantly higher [2 h:(0.36 ±0.09),3 h:(0.38 ±0.01),4 h:(0.44 ± 0.06),8 h:(0.30 ± 0.09),control group:(0.24 ± 0.01),P ＜ 0.05].The level of serum sE-selectin gradually increased after intraperitoneal injection of LPS,reached the peak at 2 h,and then decreased gradually.The level of sE selection was significantly higher than that of the control group at the point of 2 h,3 h,4 h and 8 h (P ＜ 0.05).The level of serum sE-selectin increased along with the expression of E-selectin in lung tissues,and they were positively correlated (r =0.730,P ＜ 0.01).Conclusion The increased expression of E-selectin and the elevation of serum sE-selectin level may reflect the injury of pulmonary vascular endothelial cells induced by systemic inflammatory response.