ABSTRACT
Objective To investigate the protective effect and mechanism of hyperoside(HYP)on paraquat(PQ)-induced acute lung injury in rats.Methods Rats were randomly divided into the control group,the PQ group,the low-dose hyperoside group(HYP-L group),the middle-dose hyperoside group(HYP-M group)and the high-dose hyperoside group(HYP-H group),with 12 rats in each group.After 7 days of corresponding treatment,the levels of interleukin(IL)-1β,IL-6 and macrophage inflammatory protein-2(MIP-2)in bronchoalveolar lavage fluid(BALF)of rats in each group,as well as the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in lung tissue were detected.The degree of lung injury and fibrosis of rats were evaluated by hematoxylin-eosin(HE)staining and Masson's trichrome staining.The expression levels of E-cadherin,α-smooth muscle actin(α-SMA),Vimentin,and protein expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),nuclear factor-κB(NF-κB)p65,p-NF-κB p65,transforming growth factor-β1(TGF-β1),Smad3 and p-Smad3 in lung tissue were detected by Western blot.Results Compared with the control group,the levels of IL-1β,IL-6 and MIP-2 in BALF of rats in the PQ group increased(P<0.05),the level of SOD in the lung tissue decreased,while the level of MDA increased(P<0.05),and the lung tissue showed obvious damage and fibrosis(P<0.05).Compared with the PQ group,the levels of IL-1β,IL-6 and MIP-2 in BALF of rats in the HYP-L group,the HYP-M group and the HYP-H group decreased(P<0.05),the levels of SOD in the lung tissue increased(P<0.05),while the levels of MDA decreased(P<0.05),and the lung tissue damages were alleviated,and the fibrosis score decreased(P<0.05).Compared with the control group,the expression level of E-cadherin in the lung tissue of rats in the PQ group decreased(P<0.05),the expression levels of α-SMA and Vimentin increased(P<0.05),the protein expression level of Nrf2 decreased(P<0.05),the protein expression level of TGF-β1 and the phosphorylation levels of NF-κB p65 and Smad3 proteins increased(P<0.05).Compared with the PQ group,the expression levels of E-cadherin in the lung tissues of rats in the HYP-L group,the HYP-M group and the HYP-H group increased(P<0.05),the expression levels of α-SMA and Vimentin decreased(P<0.05),the protein expression levels of Nrf2 increased(P<0.05),the protein expression level of TGF-β1 and the phosphorylation levels of NF-κB p65 and Smad3 proteins decreased(P<0.05).Conclusion Hyperoside effectively alleviates paraquat-induced acute lung injury in rats,and it may reduce lung oxidative stress,inflammation and fibrosis by regulating Nrf2,NF-κB and TGF-β1/Smad2/3 signal pathways.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the significance of changes in plasma high mobility group box-1 protein (HMGB1) levels and its relationship with sepsis and endotojemia in severely burned patients.</p><p><b>METHODS</b>Totally 25 large area burned patients ( > 30% total body surface area) were included in this study, and 8 healthy volunteers served as normal controls. The plasma levels of HMGB1 were measured by ELISA, and endotoxin concentrations was determined by the modified chromogenic limulus amebocyte lysate (LAL) assay on posthurn days 1, 3, 5, 7, 14, 21, and 28.</p><p><b>RESULTS</b>The plasma HMGBL levels were markedly elevated on postburn day 1 in severely burned patients, and they were significantly higher in septic patients than those without sepsis on days 7, 21, and 28 after burns (P<0.05). Among septic patients, plasma HMGBI levels in the survival group were significantly lower than those with fatal outcome on days 3 and 21 (P<0.05, P<0.01). No significant correlations were found between HMGB1 levels and the sizes of total body surface area (P>0.05). In addition, the plasma HMGB1 levels were positively correlated with endotoxin concentrations on days 3, 5, 7, 21 after major burns (P<0.05, P<0.01).</p><p><b>CONCLUSIONS</b>HMGB1, as an important late mediators of inflammation, may be involved in the development of sepsis following extensive burns, and it can be markedly induced by endotoxemia secondary to acute insults. Dynamic measurements of circulating HMGB1 levels should be helpful to monitor the disease course and judge the prognosis of burned patients.</p>