RESUMO
Objective To investigate the therapeutic role and potential mechanisms of astaxanthin (ASX) pretreatment on cecal ligation and puncture (CLP)-induced sepsis in mice .Methods Sepsis was induced by CLP in male mice ,which were then randomly divided into saline control group ,sepsis model group (CLP group) ,and CLP+ASX group (mice received 60 mg/(kg · d) ASX dissolved in olive oil via oral gavage for 14 consecutive days before CLP operation) .① The mice were monitored to assess 72-hour survival rate .② Clinical scores of mice in the three groups were calculated 24 h after CLP to determine the severity of sepsis .Blood samples were collected at 24 h after CLP modeling to determine the serum ALT ,BUN ,TNF-α and IL-6 levels .The intestine ,lung ,liver and kidney tissues were collected to assess organ functions and pathological changes .Results The results showed that mice in CLP group had a significantly lower survival rate at 72 h than those in CLP+ASX group (P=0 .0202) .CLP+ASX sepsis group had a lower clinical score than CLP sepsis group(10 .78 ± 0 .79 vs .13 .67 ± 0 .44 ,P=0 .005) .The tissue histopathology and biochemical analysis revealed that ASX markedly alleviated histological examination damage in the intestines [villus height :(390 .67 ± 14 .58)μm vs .(326 .67 ± 10 .31)μm , P=0 .005] ,lung (lung wet/dry ratio :4.75±0.24 vs.5.05±0.22,P=0.0476),liver[ALT:(105.0±10.53)U/L vs.(174.8±9.289)U/L,P=0.0006] and kidney [BUN:(54 .50 ± 3 .57)mg/dL vs .(69 .17 ± 3 .33)mg/dL , P= 0 .0132] tissues in sepsis .Moreover , significant lower levels of TNF-α [(258 .06 ± 16 .21 )pg/mL vs . (538 .17 ± 30 .80 )pg/mL , P< 0 .0001 ] and IL-6 [(5 .90 ± 0 .80)ng/mL vs .(12 .56 ± 0 .55)ng/mL , P<0 .0001] were discovered in the CLP+ ASX sepsis group in contrast to the CLP sepsis group .Conclusion ASX can significantly lower the mortality of mice with CLP-induced sepsis by improving organ functions and inhibiting the release of inflammatory factors .
RESUMO
<p><b>BACKGROUND</b>Rosiglitazone is known as the most potent and specific peroxisome proliferators-activated receptor gamma (PPAR-gamma) ligand. It has potentially far-reaching effects on pathophysiological processes, from cancer to atherosclerosis and diabetes. However, it is not clear whether rosiglitazone affects the protein expression of transforming growth factor beta3 (TGF-beta3) and the cell proliferation in human uterine leiomyoma cells in vitro.</p><p><b>METHODS</b>Human uterine leiomyoma tissues were dissected and cultured. Cells were divided into 5 groups: one control group and other four groups with different concentrations of rosiglitazone (10(-7), 10(-8), 10(-9) and 10(-10) mol/L). Cells were cultured for 72 hours in serum-free Dulbecco's modified Eagle's medium. MTT reduction assay was used to detect the cell proliferation. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of PPAR-gamma and TGF-beta3. Immunofluorescence staining was used to detect the expressions of PPAR-gamma and TGF-beta3 proteins.</p><p><b>RESULTS</b>MTT reduction assay indicated that the treatment with rosiglitazone (from 10(-7) to 10(-9) mol/L) resulted in an inhibition of the cell growths after 72 hours (P < 0.01). RT-PCR analysis revealed that 10(-7) mol/L rosiglitazone significantly affected the gene expression at 72-hour: PPAR-gamma mRNA expression was up-regulated and TGF-beta3 mRNA was down-regulated and rosiglitazone at the concentration of 10(-7) mol/L affected these most effectively (P < 0.01). Immunofluorescence staining demonstrated that treatment with 10(-7) mol/L rosiglitazone resulted in the significant changes of PPAR-gamma and TGF-beta3 protein expressions compared with the other treatment groups and the control group at 72-hour (P < 0.01). All the effects of rosiglitazone on uterine leiomyoma cells were dose- and time-dependent in vitro.</p><p><b>CONCLUSIONS</b>The present study demonstrates that the PPAR-gamma activator, rosiglitazone, inhibits the cell proliferation partly through the regulations of PPAR-gamma and TGF-beta3 expressions. The cross-talk between the signal pathways of PPAR-gamma and TGF-beta3 may be involved in the process.</p>