RESUMO
Obstructive jaundice (OJ) is a common disease in clinical surgery. The present study aimed to determine the effects of dexmedetomidine (Dex) on hepatocyte apoptosis in rats with OJ and also to explore the underlying mechanism. A total of 30 adult male Sprague Dawley rats were randomly divided into 3 groups: Sham group, bile duct ligation (BDL) group, and BDL+Dex group. The serum liver function index, expression levels of serum inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and the liver pathological changes were compared amongst groups. The serum liver function index and expression levels of inflammatory factors in the BDL group and BDL+Dex group were higher compared with the sham group. The serum liver function index and expression levels of inflammatory factors were lower in the BDL+Dex group compared with the BDL group. The severity of hepatic injury was diminished in the BDL+Dex group compared with the BDL group. Compared with the sham group, the hepatocyte apoptosis rate increased significantly in the BDL group and BDL+Dex group. The present findings suggested that Dex improved the liver function of rats with OJ, reduced the production of inflammatory factors and inhibited the apoptosis of hepatocytes. Dex demonstrated a protective effect on liver damage potentially via activation of the phosphoinositide 3-kinase/protein kinase B signaling pathway.
RESUMO
BACKGROUND: Obstructive jaundice (OJ) could seriously affect the biochemical and immune functions in the body. Up to now, there are still poor evidences about the role of dexmedetomidine in OJ. METHODS: Male Wistar rats were divided into four groups: Sham operation group (Sham group, n = 10), obstructive jaundice group (OJ group, n = 10), OJ + dexmedetomidine group (D group, n = 10), OJ+ dexmedetomidine +LY294002 group (DL group, n = 10). The expressions of phospho-Akt(p-Akt), HIF-1α(hypoxia inducible factor-1α), Akt mRNA, HIF-1αmRNA, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in different groups were evaluated. RESULTS: The lung injury score was decreased in OJ group compared with that in DL group. The expression of the HIF-1α protein, p-Akt protein, Akt mRNA, and HIF-1α mRNA in OJ group were significantly increased (p <0.05) (vs. S group). Meanwhile, these protein molecular were significantly higher in the D group than that in OJ group (p <0.05). However, the mRNA expressions of these molecular in OJ group were significantly lower than that in D group (p <0.05). The concentrations of IL-6 and TNF-α in OJ group and D group was significantly up-regulated compared with that in S group (p <0.05). Meanwhile, IL-6 and TNF-α concentrations were significantly up-regulated in DL group compared with that in group D (p <0.05). The concentrations of IL-6 and TNF-α were significantly decreased in the D group and DL group compared with that in OJ group (p <0.05). CONCLUSION: Dexmedetomidine can attenuate lung injury in obstructive jaundice rats through PI3K/Akt/HIF-1α signaling pathway. Meanwhile, dexmedetomidine can reduce the concentrations of IL-6 and TNF-α in obstructive jaundice rats.
