The Protective Effect Of Dexmedetomidine On Liver Injury During Sepsis And Its Possibility Mechanism

Objective To observe the effects of different concentration of dexmedetomi- dine(DEX) on the influence of inflammatory cytokine, ornithine carbamyl transferase(OCT), signal transducers and activations of transcription 3(STAT3) in rats with sepsis. To investigate the protective effects of liver injury and the possible mechanism, try to provide theoretical basis for clinical treatment of sepsis.Methods The experiment included two parts. Part one: 100 healthy SD rats were randomly divided into five groups(n=20): sham operation group(S group), cecal ligation and puncture model group(P group), dexmedetomidine 2.5μg·kg-1·h-1 group(D1 group), dexmedetomidine 5μg·kg-1·h-1 group(D2 group) and dexmedetomidine 10μg·kg-1·h-1 group(D3 group). The rats in S group only opened celiac flip the cecum, the rats in other groups had cecal ligation and puncture(CLP) surgery to establish model of sepsis-induced liver injury. Each rats in D1、D2、D3 groups were injected in caudal vein with corresponding concentration of DEX at 0.5 hours after the surgery respectively, DEX were diluted into 5ml?kg-1?h-1 with duration of 0.5 hours, while S group and P group received equal volume of normal saline instead.Part two: according to the results of first part, 100 healthy SD rats were randomly divided into five groups in the same model(n=20): sham operation group(S group), cecal ligation and puncture model group(P group), DEX 10μg·kg-1·h-1 group(D group), yohimbine and DEX 10μg·kg-1·h-1 group(DY group), and yohimbine group(Y group). D group and DY group were injected in caudal vein with 10μg?kg-1?h-1 of DEX at 0.5 hours after the surgery, DEX were diluted into 5ml?kg-1?h-1 with duration of 0.5 hours, while S group、P group and Y group received equal volume of normal saline instead. DY group and Y group were injected in caudal vein with 1mg ?kg-1 of yohimbine, the duration of infusion was not less than 5 minutes.Rats’ livers in each group were took bleed to death at 6h, 12 h after the surgery, respectively. Liver homogenate cytokine concentrations(IL-6、IL-10) and ornithine carbamoyl transferase(OCT) concentrations were measured by enzyme-linked immunosorbent assay(ELISA), Signal Transducer and Activator Of Transcription 3(STAT3) protein concentration were measured by western blotting,and histopathological examinations on liver tissues were observed under light microscope.Results Part one: the concentrations of IL-6、IL-10、OCT from liver homogenate increased significantly in P、D1、D2 and D3 groups when compared with S group at each time point, and the expression of STAT3 obviously up-regulated(all P<0.05), and liver tissue had different degree of pathological damage. Compared with P group at each time, IL-6、IL-10、OCT and STAT3 in the D1、D2、D3 groups declined dramatically(all P<0.05), and the histopathological damages in liver tissues were well ameliorated. When compared to P group, all examination indicators in D1、D2 and D3 group gradually declined at the same time point, and the histopathological damages in liver tissues were well ameliorated. Among them, the indicators of D3 group were the lowest, and liver tissue damages in D3 were the lightest.Part two: compared with S group at the same time, the concentration of IL-6、IL-10 and OCT in P、D、DY and Y groups were increased significantly at 6h and 12 h after CLP, and STAT3 was up-regulated expression obviously(all P<0.05), and the liver tissue had different degree of pathological damages; Compared with P、DY and D groups at each time point, IL-6、IL-10、OCT and STAT3 in D group declined dramatically(all P<0.05); Compared with P and Y group, concentration of IL-6、IL-10 and OCT in DY group were reduced, STAT3 also reduced in DY group at each time point(all P<0.05); Compared Y group with P group at the same time, there was no significant difference in the concentration of IL-6、IL-10 、OCT and STAT3(all P>0.05).Conclusion Dexmedetomidine has a protective effect on liver injury in septic rats, in a dose-dependent manner. The protective mechanism may be connected with alpha-2 adrenergic receptor, and down-regulation of STAT3 may contribute to the protective.