Observation Of The Dose-effect And Time-effect Relationship In Rabbits Between LPS And Renal Injury Induced By Endotoxin

ObjectiveTo find a general rule of renal function damage in different level of endotoxemia model rabbit during the first 5 hours and further provide a reference for clinical treatment of endotoxemia.MethodsForty-eight big-eared rabbits were randomly divided into 4 groups:normal control group, low-dose of LPS group(100μg/kg), middle-dose of LPS group(200μg/kg) and high-dose of LPS group(400μg/kg). The normal control group included 3 rabbits, and the other groups were 15 of each (3 rabbits for every time point). According to the weight and group, each rabbits were injected with different dose of LPS dissolved in 5ml NS. The normal control group were injected with 5ml NS without LPS in ten minutes. The observation was started after the injection was completed. There were 5 time points as follows:1st hour(T1),2nd hour(T2),3rd hour(T3),4th hour(T4) and 5th hour(T5). Each time point, every group had 3 rabbits to be dealt with anaesthetizing and then the blood sample were drawn to measure Urea and Scr, urine were collected from the bladder for electropHoresis, and then the kidneys were dissected for pathology and immunol histochemistry assay.ResultsThe normal control group's Urea from T1 to T5 were as follows:6.0±0.9,6.1±1.0, 6.1±0.9,6.1±1.0,6.2±1.1mmol/L, Scr from T1 to T5 were as follows:59±13,59±10, 59±12,58±10,59±12μmol/L. While the low-dose of LPS group's Urea (from T1 to T5 were as follows:6.4±1.2,7.7±1.8,8.2±0.9,9.1±1.2,10.7±1.1mmol/L)was significantly increased at T4(P<0.05), Scr(from T1 to T5 were as follows:55±15,64±19,81±17, 111±15,121±17μmol/L)was significantly increased at T4(P<0.05); middle-dose of LPS group's Urea (from T1 to T5 were as follows:7.0±1.8,8.4±1.7,9.2±1.3,9.6±1.4, 11.8±1.8mmol/L) was significantly increased at T3(P<0.05), Scr(from T1 to T5 were as follows:71±7,77±9,97±8,122±14,152±11μmol/L)was significantly increased at T3(P<0.05);high-dose of LPS group's Urea (from T1 to T5 were as follows:9.4±1.2, 10.8±1.5,12.1±1.9,12.7±1.8,13.8±1.2mmol/L)was significantly increased at T1(P<0.05), Scr(from T1 to T5 were as follows:84±9,101±6,126±14,158±16, 206±23μmol/L)was significantly increased at T1(P<0.05). The significantly different result of the urine electropHoresis was demonstrated at T5 in low-dose of LPS group, T4 in middle-dose of LPS group, T3 in high-dose of LPS group, the similar results were also observed in the tests of pathology and immunol histochemistry assay.ConclusionAll of the three treatment groups appeared azotemia before kidney pathological injury were observed. Urea and Scr were significantly increased, and tubular proteinuria were observed. Kidney injury induced by endotoxin became worsened on a dose-effect and time-effect dependent style.