ABSTRACT
AIM:To investigate the effects of dexmedetomidine on hemorrhagic shock /resuscitation(HS/R)-induced acute kidney injury(AKI)in rats,and to explore the possible mechanisms.METHODS:Wistar rats(n=32) were randomly divided into 4 groups(n =8): normal saline control group(NS group), dexmedetomidine group(D group),HS/R group and HS/R+D group.The animals were sacrificed at 6 h after resuscitation.The levels of serum creatinine(Cr)and blood urine nitrogen(BUN)were examined.The kidneys of all rats were removed for evaluation of histological characteristics,and the levels of malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β (IL-1β)and superoxide dismutase(SOD)were measured.The expression of nuclear factor-κB(NF-κB)and hemeoxyge-nase-1(HO-1)was determined by Western blot.RESULTS: Compared with NS group, the levels of Cr, BUN, MDA, TNF-αand IL-1βwere obviously increased in HS/R group, which were obviously decreased in HS/R+D group(P<0.05).Compared with NS group,the SOD activity was obviously decreased in HS/R group,which was obviously increased in HS/R+D group(P<0.05).Compared with NS group, the protein expression of NF-κB was obviously increased in HS/R group,which was obviously decreased in HS/R+D group(P<0.05).Compared with NS group, the protein ex-pression of HO-1 was increased in HS/R group.Compared with HS/R group,the protein expression of HO-1 was obviously increased in HS/R+D group.Compared with NS group,HS/R induced marked kidney histological injury,which was less pronounced in HS/R+D group.CONCLUSION:Dexmedetomidine effectively protects rats against AKI caused by HS /R, and its mechanism may be associated with the increase in HO-1 expression and the inhibition of NF-κB expression.
ABSTRACT
This study aims to elucidate the mechanisms by which dexmedetomidine alleviates pulmonary edema in rats with acute lung injury induced by lipopolysaccharide (LPS). Male Wistar rats were randomly divided into five groups: normal saline control (NS) group, receiving intravenous 0.9% normal saline (5 mL/kg); LPS group, receiving intravenous LPS (10 mg/kg); small-dose dexmedetomidine (S) group, treated with a small dose of dexmedetomidine (0.5 μg · kg(-1) · h(-1)); medium-dose dexmedetomidine (M) group, treated with a medium dose of dexmedetomidine (2.5 μg · kg(-1) · h(-1)); high-dose dexmedetomidine (H) group, treated with a high dose of dexmedetomidine (5 μg · kg(-1) · h(-1)). The rats were sacrificed 6 h after intravenous injection of LPS or NS, and the lungs were removed for evaluating histological characteristics and determining the lung wet/dry weight ratio (W/D). The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in the lung tissues were assessed by enzyme- linked immunosorbent assay (ELISA). The mRNA and protein expression levels of aquaporin-1 (AQP1) and aquaporin-5 (AQP5) were detected by RT-PCR, immunohistochemistry, and Western blotting. The lung tissues from the LPS groups were significantly damaged, which were less pronounced in the H group but not in the small-dose dexmedetomidine group or medium-dose dexmedetomidine group. The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group as compared with those in NS group, which were reduced in the H group but not in S group or M group (P<0.01). The expression of AQP1 and AQP5 was lower in the LPS group than in the NS group, and significantly increased in the H group but not in the S group or M group (P<0.01). Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing the expression of AQP-1 and AQP-5.