[Effect of dexmedetomidine on expression of tight junction protein ZO-1 in kidney tissue of rats with acute kidney injury induced by sepsis].

OBJECTIVE To observe the effect of dexmedetomidine (DEX) on the expression of tight junction protein ZO-1 in kidney tissues of rats with acute kidney injury (AKI) induced by sepsis. METHODS Sixty healthy male Sprague-Dawley rats were selected and divided into four groups: sham operation group (Sham group), DEX + Sham group, cecal ligation and puncture (CLP) group and DEX + CLP group according to a random number table, with 15 rats in each group. Each group was then divided into 3 subgroups at 6, 12, and 24 hours after the operation, with 5 rats in each subgroup. Modified CLP was used to establish a sepsis model. In Sham group and DEX + Sham group, only laparotomy and abdominal closure were performed. Each group was given pretreatment 1 hour before modeling. DEX + Sham group and DEX + CLP group were pumped into DEX at a rate of 5 μg×kg-1×h-1 through the caudal vein; Sham group and CLP group were pumped with the equal amount of normal saline through the caudal vein. Rats in each group were sacrificed at 6, 12, and 24 hours after operation to obtain kidney tissue. After hematoxylin-eosin (HE) staining, the pathological changes were observed under a light microscope, and the pathological score of renal injury was calculated. The positive expression level of ZO-1 in kidney tissue was detected by immunohistochemistry. RESULTS The pathological changes of rat kidney tissue could be seen at 6 hours after CLP. With the prolongation of postoperative time, the degree of renal injury showed a tendency to aggravate, with 24 hours being more significant. Semi-quantitative analysis showed that compared with the Sham group, the CLP group had significantly higher renal injury pathology scores at each time point (1.98±0.37 vs. 0.36±0.25 at 6 hours, 2.62±0.34 vs. 0.39±0.18 at 12 hours, 3.52±0.34 vs. 0.42±0.20 at 24 hours,all P < 0.01); the positive expression level of ZO-1 in kidney tissue was significantly reduced [percentage of positive area: (3.17±0.74)% vs. (10.83±0.83)% at 6 hours, (2.56±0.76)% vs. (9.02±0.88)% at 12 hours, (1.75±0.66)% vs. (8.25±0.94)% at 24 hours, all P < 0.01]. Compared with the CLP group, the pathological score of renal injury in the DEX + CLP group was significantly reduced at each time point (0.66±0.27 vs. 1.98±0.37 at 6 hours, 1.34±0.26 vs. 2.62±0.34 at 12 hours, 2.08±0.38 vs. 3.52±0.34 at 24 hours, all P < 0.01); the positive expression level of ZO-1 in kidney tissue was significantly increased [percentage of positive area: (8.58±0.86)% vs. (3.17±0.74)% at 6 hours, (7.44±1.05)% vs. (2.56±0.76)% at 12 hours, (6.60±0.87)% vs. (1.75±0.66)% at 24 hours, all P < 0.01]. There was no significant difference in renal injury pathology score and ZO-1 positive expression between the DEX+Sham group and the Sham group. CONCLUSIONS DEX may reduce sepsis-induced AKI in rats by up-regulating the expression of tight junction protein ZO-1 in kidney tissue.