Investigation Of The Common Mechanisms From Inflammatory Water- Fluid Dysbolism By Different Animal Modeling Methods

Objective:Through the establishment of acute lung injury(ALI), acute gastric ulcer(AGU) and chronic renal failure (CRF) animal models to investigate the changes of inflammatory cytokines and expression of aquaporins, we probe into the common mechanisms from inflammatory water-fluid dysbolism by different causes, which could provide a basis for prevention, treatment and therapeutic drug development of inflammatory water-fluid dysbolism.Methods:Several male Wistar rats of 6-8-week old were taken for 3 experiments. Wistar rats were randomly divided into 3 groups by weights in each experiment. The 3 groups included normal group, model group and intervention group. ALI, AGU, CRF were modeling respectively by injection of lipopolysaccharide, intragastric administration of ethanol, intragastric administration of adenine suspension, then we take dexamethasone, ranitidine and prednisone for drug intervention. When taken anesthesia after model establishment, blood were collected to detect serum levels of inflammatory cytokines. The rats were killed after anesthesia and target organs were used for HE staining to observe pathological changes. Real-time PCR, Western Blotting and Immunohistochemical Staining were used for measuring mRNA and protein expression of aquaporins in target organs.Results:General signs of rats with acute lung injury were weak, these rats were in poor mental state. Compared to the normal group, lung index, serum tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), interleukin-6(IL-6) were significantly increased (P<0.05). Expression level of AQP1 in lung was significantly decreased (P<0.05), while expression level of AQP5 in lung wasn’t decreased notably (P>0.05).After administration of dexamethasone, general signs of these rats were improved. Compared to the model group, lung index, serum TNF-α, CRP and IL-6 were significantly decreased (P<0.05), expression level of AQP1and AQP5 in lung as well as expression level of AQP1 in spleen were significantly decreased (P<0.05). Structures of lung tissues in normal group were clear and complete. However the alveolar septum of lung in model group were obviously thicken, alveolar wall were infiltrated by neutrophils and lymphocytes.Rats with acute gastric ulcer were in poor mental state. Compared to the normal group, serum TNF-α and IL-6 of model group rats were significantly increased (P<0.05). Expression level of AQP1 in both stomach, expression level of AQP3 in stomach and stomach index weren’t increased notably (P>0.05). After administration of ranitidine, mental state of these rats was improved. Compared to the model group, serum TNF-a, IL-6 were significantly decreased (P<0.05), and the expression level of AQP3 in stomach as well as expression level of AQP1 in spleen were decreased. However the expression level of AQP1 in stomach increased. Gastric mucosas of normal group rats were regular in shape while gastric mucosa of model group rats were blurred, inflammatory cells were observed.Rats with chronic renal failure were in quite poor mental state. Compared to the normal group, kidney index, serum TNF-a, CRP, IL-6 and expression level of AQP2 in kidney were significantly increased (P<0.05). Expression level of AQP1 in kidney was significantly decreased (P<0.05).After administration of prednisone for several days, general signs of these rats were improved. Compared to the model group, expression level of AQP1 in kidney was significantly increased (P<0.05), kidney index, serum CRP content as well as expression level of AQP2 in kidney were decreased. Renal tubules of normal group rats were packed tightly; however, there were severe expansion of renal tubules in model group. Glomerular of model group rats were damaged with infiltration by inflammatory cells and the border area showed hyaline change.Conclusions:Serum inflammatory cytokines TNF-a, CRP and IL-6 showed different degrees of increase among these three models.While inflammatory water-fluid dysbolism occurred in target organs with decreased expression of AQP1,other AQPs had abnormal expressions,too.Therefore,we concluded that among inflammatory water-fluid dysbolism induced by different causes, manifestations and targets of abnormal expressions of AQPs might have differences.