目的:观察右美托咪定（DEX）对脓毒症急性肾损伤（AKI）大鼠肾组织紧密连接蛋白ZO-1表达的影响。方法:选取60只清洁级健康雄性SD大鼠，按随机数字法分为4组：假手术组（Sham组）、DEX+Sham组、盲肠结扎穿孔术（CLP）组和DEX+CLP组，每组15只；各组再按术后6、12、24 h分为3个亚组，每个亚组5只。采用改良CLP制备脓毒症模型，Sham组和DEX+Sham组仅开关腹。各组于制模前1 h给予预处理，DEX+Sham组和DEX+CLP组经尾静脉以5 μg·kgn -1·hn -1的速度泵入DEX；Sham组和CLP组经尾静脉泵入等量生理盐水。分别于术后6、12、24 h处死各组大鼠取肾组织，苏木素-伊红（HE）染色后，光镜下观察其病理学改变，并进行肾损伤病理学评分；采用免疫组化法检测肾组织中ZO-1的阳性表达水平。n 结果:CLP术后6 h即可见大鼠肾组织病理学改变，随着术后时间延长，肾损伤程度表现为加重趋势，以24 h更为显著。半定量分析显示，与Sham组相比，CLP组各时间点肾损伤病理学评分明显升高（分：6 h为1.98±0.37比0.36±0.25，12 h为2.62±0.34比0.39±0.18，24 h为3.52±0.34比0.42±0.20，均n P<0.01），肾组织ZO-1阳性表达水平显著降低〔阳性面积百分比：6 h为（3.17±0.74）%比（10.83±0.83）%，12 h为（2.56±0.76）%比（9.02±0.88）%，24 h为（1.75±0.66）%比（8.25±0.94）%，均n P<0.01〕；与CLP组相比，DEX+CLP组各时间点肾损伤病理学评分均明显降低（分：6 h为0.66±0.27比1.98±0.37，12 h为1.34±0.26比2.62±0.34，24 h为2.08±0.38比3.52±0.34，均n P<0.01），肾组织ZO-1阳性表达水平明显升高〔阳性面积百分比：6 h为（8.58±0.86）%比（3.17±0.74）%，12 h为（7.44±1.05）%比（2.56±0.76）%，24 h为（6.60±0.87）%比（1.75±0.66）%，均n P<0.01〕；DEX+Sham组与Sham组肾损伤病理学评分和ZO-1阳性表达水平比较差异均无统计学意义。n 结论:DEX可能通过上调肾组织紧密连接蛋白ZO-1的表达减轻脓毒症大鼠AKI。“,”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 n -1·hn -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.n 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 n 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 n 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 n 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 n 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.n Conclusion:DEX may reduce sepsis-induced AKI in rats by up-regulating the expression of tight junction protein ZO-1 in kidney tissue.