右美托咪定对大鼠肾缺血-再灌注损伤的保护作用  

Renoprotective effects and mechanism of dexmedetomidine on renal ischemia/reperfusion injury in rats

作　　者：斯妍娜[1] 鲍红光[1] 张勇[1] 蔡朦朦[1] 蒋卫清[1] 尹加林[1] 徐磊[1] 

机构地区：[1]南京医科大学附属南京医院南京市第一医院麻醉科,210006

出　　处：《临床麻醉学杂志》2013年第3期261-264,共4页Journal of Clinical Anesthesiology

基　　金：南京市医学科技发展项目(201108028);南京医科大学科技发展基金项目(2010NJMU052)

摘　　要：目的观察右美托咪定(DEX)对肾缺血-再灌注损伤(IRI)大鼠肾脏细胞凋亡和炎症因子的影响并探讨其机制。方法健康雄性Wistar大鼠40只,体重220～300g,随机均分为四组:缺血-再灌注组(IR组)、阿替美唑+右美托咪定组(AD组)、右美托咪定组(DEX组)和对照组(C组)。IR、AD、DEX组无损伤血管夹夹闭双侧肾蒂45min建立肾IRI模型,C组只行假手术。AD组和DEX组分别在缺血前30min腹腔注射25μg/kgDEX,C组和IR组给予等容量生理盐水。AD组在注射DEX前腹腔注射250μg/kg阿替美唑。再灌注24h后取肾组织观察组织病理学改变和细胞凋亡,测定JAK2、STAT3、p-JAK2和p-STAT3表达;取血标本测定血清肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-10水平。结果与IR和AD组比较,DEX组的肾组织病理学改变减轻,细胞凋亡数量减少,JAK2、STAT3、p-JAK2、p-STAT3、TNF-α和IL-6水平降低,IL-10水平增加(P<0.05)。结论肾IRI时DEX通过抑制JAK2/STAT3通路而调控炎性因子水平,减轻肾组织炎症反应和减少细胞凋亡,缓解组织损伤。Objective To observe the effects of dexmedetomidine （DEX） on renal cell apoptosis and inflammatory factors against renal ischemia/reperfusion injury （IRI） in rats and investigate its mechanism. Methods Forty healthy male Wistar rats, weighing 220-300 g, were randomly allocated into 4 groups., control group （group C）, isehemia/reperfusion group （group IR）, atipamezole combined with dexmedetomidine group （group AID） and dexmedetomidine group （group DEX）. We established the IRI model via clamping both renal pedicles of rats for 45 min with non-traumatic vascular clamps. Rats in control group underwent sham surgery only. Rats in the groups AD and DEX received dexmedetomidine 25 μg/kg via intraperitoneal injection 30 min before renal ischemia. Rats in the groups C and IR receive the same volume of saline only. Rats in the group AD were treated with atipamezole （250 μg/kg） prior to the administration of dexmedetomidine. At 24 h after reperfusion, renal tissue was obtained to observe histopathological changes and apoptosis, and to detect the expression of JAK2, STAT3, p-JAK2 and p-STAT3. The blood sample was obtained to detect the level of TNF-a, IL-6 and IL-10. Results Compared with groups IR and AD, there were less histopathological changes, less numbers of apoptosis cells, less expression of JAK2, STAT3, p-JAK2, p-STAT3, TNF-a, IL-6, and higher expression of IL-10 in group DEX （P〈0.05）. Conclusion The administration of dexmedetomidine against renal IRI may regulate inflammatory factors via suppressing JAK2/STAT3 pathway, attenuate the renal inflammatory responses, suppress apoptosis, and lessen the injury of renal tissue.

关 键 词：缺血-再灌注损伤 右美托咪定 炎症因子 细胞凋亡 JAK2 STAT3通路 

分 类 号：R614[医药卫生—麻醉学]