The roles of Ginkgolide B in the protection of intestine against endotoxemia in young rats / 中华急诊医学杂志

ABSTRACT

Objective Gastrointestinal dysfunction is closely correlated with the impairment of intestinal barrier caused by serious infection.We focused on the role of platelet activating factor(PAF)in the intestinal impairment caused by endotoxemia by studying on the morphology of intestinal epithelial ceils and diamine oxidase (DAO)levels with the application of Ginkgolide B(PAF receptor antagonist).Method Eighteen-day-old Wistar rats were randomized into lipopolysaccharide(LPS)(5 mg/kg),PAF receptor antagonist(pretreatment and treatment)and normal saline(Control)groups(n=8 at each time point).Ginkgolide B(PAF receptor antagonist BN52021)5 mg/kg was administered 30 minutes before(in pretreatment group)and after LPS injection(in treatment group).The ileum specimens(n=8)were harvested at 1.5,3,6,24,48 and 72 hours after LPS or NS injection.The ultrastructures of intestinal epithelial cells were studied by transmission electron microscopy (TEM)and with hematoxylin and erosin staining.The contents of DAO in ileum tissue and plasma were measured respectively with spectrophotometer.According to data Normality and Variance equality,ANOVA analysis and LSD (least significant difference)-t test were used for multiple group difference.The whole test Was performed in the animal laboratory,pathological laboratory,biochemical laboratory of our hospital and electron microscopy laboratory of Liao-ning University of Traditionary Chinese Medicine.Results Histologic examination of intestinal injury in LPS group showed the edema of intestinal villi,the capillary congestion in lamina propria,the dilation of interstitial lymphatic vessel.and the polymorphonuclear infiltration in enteric cavity in LPS group at 1.5,3,6,24 hours.The edema of the intestinal villi were shown in antagonist group.Ultrastructural study showed microvilli and tight junctions were intact in the control group.The tight junctions enlarged and the microvilli were thin,rare or disrupted in the experimental group.The pathological changes in PAF antagonist group were slightly lighter than that in the LPS group.The DAO content in the ileum tissue was obviously decreased in the LPS group compared with that in the control group.It reached to a nadir at 6 hrs[from(0.172±0.004)U/mg to(0.096±0.010)U/mg,F=13.372,P＜0.01).The DAO content in plasma was obviously higher in the LPS group than that in the control group.The patterns of DAO changes in the PAF antagonist group were as the same as that in the LPS group at each time point.Conclusions PAF may play a certain role in the injury of intestinal barrier in endotoxemia.Preventive and remedial administration of Ginkgolide B may relieve intestinal injury.The activity changes of DAO in plasma synchronized with that in ileum tissue.It may be deduced that the alterations of DAO in plasma may indicate the destruction of intestinal mucosa in the early stage sensitively.