小剂量氯胺酮预处理对大鼠肠缺血再灌注损伤的影响

目的 探讨小剂量氯胺酮预处理对大鼠肠缺血再灌注损伤的影响.方法 清洁级健康雄性SD大鼠48只,体重230～270 g,随机分为6组(n=8):假手术组(S组)、氯胺酮+假手术组(KS组)、肠缺血再灌注组(I/R组)、氯胺酮预处理组(K组)、锌原卟啉Ⅸ+氯胺酮预处理组(KZ组)和锌原卟啉Ⅸ组(Z组).采用夹闭肠系膜上动脉根部1 h后再灌注的方法 制备肠缺血再灌注模型.于麻醉前30 min时,S组腹腔注射生理盐水2 ml,K组和KS组均腹腔注射氯胺酮10 mg/kg,KZ组依次腹腔注射氯胺酮10 ms/kg和锌原卟啉Ⅸ5 mg/kg,Z组腹腔注射锌原卟啉Ⅸ5 mg/kg.S组、KS组仅分离肠系膜上动脉,不结扎.于再灌注6 h时处死大鼠,取肠组织测定丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性、血红素加氧酶-1(HO-1)及诱导型一氧化氮合酶(iNOS)的表达,光镜下观察肠组织病理学结果 并采用Chiu评分评价损伤程度.结果 与S组比较,I/R组、KZ组和Z组肠组织MDA含量升高,SOD活性降低,K组MDA含量升高(P<0.05或0.01),SOD活性差异无统计学意义(P>0.05),I/R组、K组、KZ组和Z组肠组织HO-1和iNOS表达上调(P<0.05或0.01),肠组织病理学损伤加重;与I/R组比较,K组肠组织MDA含量降低,SOD活性升高,肠组织HO-1表达上调,iNOS表达下调(P<0.05),肠组织病理学损伤减轻,KZ组和Z组以上指标差异无统计学意义(P>0.05).结论 小剂量氯胺酮预处理可减轻大鼠肠缺血再灌注损伤,可能与氯胺酮上调肠组织HO-1表达,下调iNOS表达有关.

Effects of low-dose ketamine pretreatment on intestinal ischemia-reperfusion injury in rats

Objective To investigate the protective effects of pretreatment with low-dose ketamine on intestinal mueosa against ischemia-reperfasion injury (I/R) and the underlying mechanism. Methods Forty-eight male SD rats weighing 230-270 g were randomly divided into 6 groups (n = 8 each) : group Ⅰ sham operation (S) ;group Ⅱ ketamine + sham operation (KS);group Ⅲ l/R;group Ⅳ ketamine + I/R (K);groupⅤ ketamine + ZnPPⅨ + I/R (KZ) and group Ⅵ ZnPPⅨ + I/R. Ketaminc 10 mg/kg and/or ZnPPⅨ 5 mg/kg were injected intraperitoneally 30 min before I/R in group Ⅳ, Ⅴ and Ⅵ. Intestinal I/R was produced by clamping of superior mesentery artery for 1 h followed by 6 h reperfusion. The animals were then killed and a segment of small intestine of 2 cm in length at about 10 cm from ileocecal valve was removed for determination of MDA content and SOD activity, HO-1 and iNOS expression and histological examination. The degree of intestinal tissue damage was graded using Chiu's scoring system (0 = normal, 5 = severe damage-exfoliation of villi, disruption of proper lamina, bleeding and ulceration). Results Intestinal MDA content was significantly increased, SOD activity was decreased and HO-1 and iNOS expression was significantly up-regulated by I/R (group Ⅲ) as compared with group Ⅰ and Ⅱ . Ketamine pretreatment significantly attenuated I/R-induced increase in MDA content and decrease in SOD activity and the protective effects of ketamine against I/R were counteracted by concomitant asministration of ZnPPⅨ. Microscopic examination showed that the pathological changes induced by I/R were significantly attenuated by ketamine and the protective effects of ketamine pretreatment against I/R were reversed by ZnPPⅨ in group Ⅴ. Conclusion Low-dose ketamine pretreatment can significantly ameliorate intestinal ischemia-reperfusion injury and up-regulation of intestinal HO-1 expression and down-regulation of iNOS are involved in the mechanism.