Experimental Studies Of Antioxidant And Anti-inflammation Therapy Intervention In Uremic Rats.

Objectives: To observe the effect of pyrrolidine dithiocarbamate(PDTC) and N-acetylcysteine(NAC) on rats with 5/6 nephrectomy(5/6Nx) model, we detected the level of serum malondialdehyde(MDA), superoxide dismutase(SOD), advanced oxidation protein products(AOPP), leukocytes interleukin-1β(IL-1β), serum free triiodothyronine(FT3) and thyroid stimulating hormone(TSH), to explore the relationship among oxidative stress, inflammation and thyroid hormone(TH), and to provide theoretical basis for clinical treatment.Methods: 24 healthy SD rats were equally randomly divided into six groups(equal numbers of males and females). Five groups were randomly selected for 5/6Nx and drawn into 5/6Nx group, PDTC group, sodium bicarbonate(SB) group, NAC group and TH group. The remaining group did not undergo 5/6Nx operation was setted as Blank group, no special treatment. Experimental doses: PDTC was intraperitoneally injected at 10mg/100 g, once daily. SB was intragastric administrated at 0.1g/100 g, once daily. NAC effervescent tablet was intragastric administrated at 80mg/100 g, once daily. Levothyroxine was intragastric administrated at 2μg/100 g, once daily. These drugs were administered for 6 weeks. The level of MDA, SOD, AOPP, IL-1β, FT3 and TSH were detected in the sixth week. SPSS19.0 software was used to analyze statistical data. Relating factors in different groups are compared by using variance analysis method.Results: 1. Serum MDA(nmol/ml), Blank group compared with 5/6Nx group, MDA content was significant increased in 5/6Nx group(P < 0.01). PDTC group, SB group, NAC group and TH group compared with 5/6Nx group, MDA level was decreased in each group(P < 0.01, P = 0.018, P < 0.01, P < 0.01). There was no significant difference in pair-wise comparison among PDTC group, SB group, NAC group and TH group(P > 0.05). 2. Serum SOD(U/ml), Blank group compared with 5/6Nx group, SOD content was significant decreased in 5/6Nx group(P <0.01). PDTC group, SB group, NAC group and TH group compared with 5/6Nx group, SOD level was increased in each group(P < 0.01, P = 0.042, P < 0.01, P < 0.01). There was no significant difference in pair-wise comparison among PDTC group, SB group, NAC group and TH group(P > 0.05) expect PDTC group and SB group(P = 0.033). 3. Serum AOPP(umol/l), Blank group compared with 5/6Nx group, AOPP level was increased significantly in 5/6Nx group(P <0.01). PDTC group, SB group, NAC group and TH group compared with 5/6Nx group, AOPP content was decreased in each group(P < 0.01, P < 0.01, P < 0.01, P = 0.021). Pair-wise comparison among PDTC group, SB group, NAC group and TH group, there were significant statistic between PDTC group and NAC group(P < 0.01), PDTC group and TH group(P = 0.01), SB group and NAC group(P < 0.01), SB group and TH group(P = 0.035), NAC group and TH group(P < 0.01). However, there was no significant statistic difference between PDTC group and SB group(P = 0.543). 4. Serum IL-1β(pg/ml), Blank group compared with 5/6Nx group, IL-1β level was elevated significantly in 5/6Nx group(P = 0.034). PDTC group, SB group, NAC group and TH group compared with 5/6Nx group, there were no significant statistic difference in each group(P = 0.612, P = 0.127, P = 0.582, P = 0.168). There was no significant difference in pair-wise comparison among PDTC group, SB group, NAC group and TH group(P > 0.05). 5. Serum FT3(fmol/ml), Blank group compared with 5/6Nx group, FT3 level was dropped significantly in 5/6Nx group(P <0.01). PDTC group, SB group, NAC group and TH group compared with 5/6Nx group, FT3 level was increased in each group(P = 0.016, P = 0.012, P < 0.01, P = 0.026). There was no significant difference in pair-wise comparison among PDTC group, SB group, NAC group and TH group(P > 0.05). 6. Serum TSH(u IU/ml), Blank group compared with 5/6Nx group, TSH content was significant increased in 5/6Nx group(P < 0.01). PDTC group, SB group, NAC group and TH group compared with 5/6Nx group, TSH level was reduced in each group(P < 0.01, P = 0.038, P < 0.01, P < 0.01). There was no significant difference in pair-wise comparison among PDTC group, SB group, NAC group and TH group(P > 0.05) expect SB group and TH group(P = 0.049).Conclusions: In CRF model, PDTC and NAC can effective reduce serum MDA, AOPP, TSH level and elevate serum SOD, FT3 level, thus improve oxidative stress and thyroid hormone levels.