Abstract
Objective To explore the influence of Thymoquinone(Thy) on kidney ischemia-reperfusion injury (IRI) and the mechanism.Methods Sixty male Sprague-Dawley rats were randomly divided into sham operation (sham)group,IRI group and IR plus different concentration of Thy preconditioning groups.Thy groups were preconditioned with Thy (5,10,20 and 40 mg/kg) by intraperitoneal injection at 45 min prior to operation,and the other 2 groups were pretreated by equal volume of saline.The rats in the IRI and Thy groups were kept in 37℃ infant incubators for 45 min after their left renal pedicles were clamped with noninvasive endoclips,and then their right kidneys were removed.The rats in the sham group underwent the same process,except for clamping the left renal pedicles.After 24-h reperfusion,blood samples and renal tissues were collected.The pathological changes of kidney tissues were observed using PAS staining.The expression levels of serum creatinine (Cr),urea nitrogen (BUN),IL-8,IFN-γ,TNF-α,MDA,CAT,GPX and SOD were measured by ELISA.The expression of JAK2,STAT3,p-JAK2,p-STAT3,p53 and p21 were measured by Western blot.Moreover,the mRNA levels of IL-8,IFN-γ and TNF-α were examined by RT-PCR.Results IRI markedly enhanced renal pathological changes and the expressions of BUN,Cr,p-JAK2,p-STAT3,p53,p21,MDA,IL-8,IFN-γ and TNF-α,meanwhile reduced the expressions of CAT,GPX and SOD.Thymoquinone pretreatment significantly decreased renal pathological changes and the expressions of BUN,Cr,p-JAK2,p-STAT3,p53,p21,MDA,IL-8,IFN-γ and TNF-α,at the same time up-regulated the expressions of CAT,GPX and SOD.There was no significant difference in the expression of JAK2 or STAT3 among the three groups.Conclusions Thymoquinone pretreatment can alleviate kidney ischemia-reperfusion injury in rats partly by inhibiting inflammation and oxidative stress mediated by JAK2/STAT3/p53 signaling pathway.关键词
百里醌/肾缺血再灌注损伤/炎症/氧化应激/JAK2/STAT3/P53Key words
Thymoquinone/renal ischemia-reperfusion injury/inflammation/oxidative stress/JAK2/STAT3/p53分类
医药卫生