Establishment Of Rat Pre-liver Failure Models And Study Of Th17/Treg Imbalance

Objective: To study the approaches for establishing pre-liver failure models in rat.Methods: Different doses of carbon tetrachloride through intraperitoneal injection to build rat models with pre-liver failure. Different doses of D-galactosamine(D-Gal N) and1ipopolysaccharide(LPS) through intraperitoneal injection to build rat models with pre-liver failure. To observe the changes of activity of rats,the changes of liver appearance,the pathology changes and serum biochemical changes of rat models to evaluate the effect of the model. Results: Liver cells swelled below 25 mg/kg dose group,but more than 50 mg/kg dose, there were chunk or large necrotic liver histology. There were hepatocyte swelling and mild necrosis below 50 mg/kg dose, but more than 500mg/kg dose, there were large necrotic liver histology. The carbon tetrachloride dose of 50mg/kg is appropriate. There were hepatocyte swelling and mild necrosis below 700mg/kg D-Gal N combined 35 ug/kg LPS dose, but more than 3500 mg/kg D-Gal N combined 175 ug/kg LPS dose, there were large necrotic liver histology. The 350mg/kg D-Gal N combined 17.5ug/kg LPS dose is appropriate. Conclusions: Using 50 mg/kg tetrachloride or 350mg/kg D-Gal N combined 17.5ug/kg LPS can both successfully establish pre-liver failure rat models. Liver appearance,liver histology and serum biochemistry changes conform to pre-hepatic failure.Objective: To study the changes of Th17, Treg and Th17/Treg in in animal models with pre-hepatic failure established with carbon tetrachloride or LPS and D-Gal N,the alterations of these cells after glucocorticoid and thymosin intervention. Methods: Put 100 ul the rat caudal vein blood into test tubes with sodium heparin for the detection of Th17 and Treg by intracellular cytokine identification using in vitro stimulation and fixation/permeabilization followed by flow cytometry. Figure out Th17/Treg. The figures were expressed with mean + standard deviation(x±s), t-test was used between different groups. HE staining and immunohistochemical staining were performed in the rats after the rats were sacrificed. Results: The animal models established in two ways had higher Th17, lower Treg and Th17/Treg dysregulation. Th17 levels in rats decreased, Treg levels increased, and Th17/Treg ratios rebalanced after glucocorticoid treatment. Th17 levels increased, Treg levels slightly decreased, and Th17/Treg ratios dysregulated after thymosin intervention. Conclusions: The Th17/Treg imbalances improved after dexamethasone intervention.Animal models occured increase Th17, slightly low Treg after thymosin intervention, therefore, dexamethasone can alleviate pre-hepatic failure,but thymosin is likely to aggravate the condition.Sequential therapy of glucocorticoid followed by thymosin may improve the condition.