Establishment Of A Model Of Multiple Organ Dysfunction Syndrome In Aged Rats

Objective: To investigate the suitable dosage of D-galactose inducing the aging model by subcutaneous injection and the reliability of this aging model. To establish a model of multiple organ dysfunction syndrome in aged rats and assess the role of lung in this MODS model.Methods: This study involves two parts. 1)Forty three-month old rats were randomly divided into 4 groups (n=10): 0.075g.kg-1 D-galactose group, 0.1g.kg-1 D-galactose group, 0.125g.kg-1 D-galactose group, and 3 -month old control group. Ten twenty-four-month rats were set as another control group. The D-galactose groups received D-galactose injected subcutaneously once per day, the two control groups were injected subcutaneously equivalent saline. The following indices were observed 40 days later: the activity of MAO-B in the brain tissue, the activity of superoxide dismutase (SOD) and the content of the lipid peroxides(LPO) in serum, the contents of lipofuscin in brain, heart and liver, the content of hemolysin in serum, the thymus weight index, the spleen weight index, the growth rate of weight, the blood sugar and cholesterol in serum. 2)Two hundred and ten 24-month old rats were randomly divided into three groups (n=70): oleic acid + lipopolysaccharide group(EOL group), oleic acid group(EO group), lipopolysaccharide group(EL group). Seventy aging models in rats induced by D-galactose were set as another oleic acid + lipopolysaccharide group(DOL group). EOL group received intravenous injection of 0.175ml/kg oleic acid at first and intravenous injection of 2.5mg/kg lipopolysaccharide eight hours later. DOL group received intravenous injection of 0.2ml/kg oleic acid at first and intravenous injection of 2.5mg/kg lipopolysaccharide eight hours later. EO group and EL group received intravenous injection of oleic acid or lipopolysaccharide respectively. After injection, all rats received 1.5L/min oxygen therapy for four hours except the 1h post-injection group. At the time before injection and then at 1,6,12,24,72,120 hours after injection, the PaO2, heart rate, respiratory rate, mean arterial pressure and the biochemical criteria of heart, liver, kidney and small intestine were measured. In addition, the incidence of MODSE and mortality of each group were observed.Results: 1) Comparing with 3-month group , the activity of MAO-B in the brain tissueand the content of the LPO of each D-galactose group and 24-month group increased respectively (P <0.01); the activity of SOD of each D-galactose group and 24-month group decreased (P <0.01); the contents of lipofuscin in brain, heart and liver increased (P <0.01); the content of hemolysin in serum, the thymus weight index and the spleen weight index of D-galactose 0.125g .kg-1 group and 24-month group decreased (P <0.01); no significant difference was found in blood sugar between D-galactose group and 3-month group; cholesterol in serum of D-galactose 0.1g/kg group increased (P <0.01); the growth rate of weight of each D-galactose group decreased (P <0.01). These changes of D-galactose 0.125g/kg group were similar to those in 24-month group (P >0.05); 2) After receiving intravenous injecting of OA, PaO2 of the EO group descended significantly (P<0.01). The descent of PaO2 of the EL group injured by LPS was not significant (P>0.05). The function changes of liver, heart, kidney and small intestine of both EO group and EL group were not significant (P>0.05). The incidence of MODSE and the mortality of EO group were 15.4% and 13.3%. The incidence of MODSE and the mortality of EL group were 17.4% and 23.3%; 3) During the time 6~24 hours after receiving intravenous injecting of OA and LPS, the PaO2 of EOL group and DOL group were less than 9.3kPa, and the alanine aminotransferase(ALT), total bilirubin(T-BIL), urea nitrogen(UREA), creatinine(CREA), aspartate aminotransferase (AST), creatine phosphokinase(CPK), diamine oxidase (DAO)　of both EOL group and DOL group were more than two times higher than that of control group before injection. The incidence of MODSE and the mortality of EOL...