盐酸羟考酮对大鼠局灶性脑缺血-再灌注损伤的影响  

Effect of oxycodone hydrochloride injection on focal cerebral ischemia-reperfusion injury in rats

作　　者：郭培培 金朝[1] 李心怡[1] 张宗泽[1] 王焱林[1] 吴会生[1] Guo Peipei;Jin Zhao;Li Xinyi;Zhang Zongze;Wang Yanlin;Wu Huisheng(Department of Anesthesiology,Zhongnan Hospital,Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院麻醉科,430071

出　　处：《中华急诊医学杂志》2020年第7期929-933,共5页Chinese Journal of Emergency Medicine

基　　金：武汉大学中南医院科技创新培育基金(znpy2018020)。

摘　　要：目的探讨盐酸羟考酮预先给药对大鼠大脑中动脉栓塞所致局灶性脑缺血-再灌注损伤的影响。方法健康雄性SD大鼠72只,体质量200~250 g,随机(随机数字法)分为三组(每组24只):假手术组(Sham组)、局灶性脑缺血-再灌注组(I/R组)和盐酸羟考酮预处理组(Oxy组)。采用大脑中动脉阻断法制备局灶性脑缺血-再灌注损伤模型,阻断2 h恢复再灌注。Oxy组于脑缺血前5 min经尾静脉注射盐酸羟考酮0.5 mg/kg,Sham组和I/R组则给予等容量生理盐水1 mL。再灌注24 h行神经功能缺陷评分(NDS);然后处死大鼠,取脑组织,测定缺血侧脑含水量,采用2,3,5-氯化三苯四唑(TTC)染色,计算脑梗死体积百分比;苏木精-伊红(HE)染色观察脑组织病理变化;ELISA法检测缺血侧脑皮质中的TNF-α、IL-1β和IL-10水平;Western blot检测脑组织NF-κB的表达水平;比色法检测脑组织髓过氧化物酶(MPO)活性。应用SPSS 20.0软件进行统计分析,计量资料多组间比较采用单因素方差分析,组间两两比较采用LSD-t检验,以P<0.05为差异有统计学意义。结果与Sham组比较,I/R组和Oxy组NDS评分、脑组织含水量、脑梗死体积百分比和细胞坏死率显著增加(均P<0.05);脑皮质中TNF-α、IL-1β、IL-10、NF-κB和MPO表达水平明显升高(均P<0.05)。Oxy组与I/R组相比,NDS评分、脑组织含水量、脑梗死体积百分比和细胞坏死率明显减少[(1.7±0.9)vs(2.6±1.1);(79.2±2.4)%vs(84.7±4.2)%;(23.0±5.4)%vs(34.8±6.0)%;(25.2±12.4)%vs(54.8±14.8)%,均P<0.05];脑皮质中TNF-α、IL-1β含量、NF-κB相对表达及MPO活性明显降低[(4.4±1.2)pg/mg vs(6.5±1.2)pg/mg;(5.4±0.7)pg/mg vs(7.8±0.8)pg/mg;(0.83±0.11)vs(1.23±0.33);(0.27±0.09)U/g vs(0.36±0.14)U/g,均P<0.05],抗炎因子IL-10水平显著升高[(20.9±4.5)pg/mg vs(9.2±1.6)pg/mg,t=6.036,P=0.0001]。结论盐酸羟考酮预先给药可明显减轻大鼠局灶性脑缺血-再灌注导致的脑损伤,其机制可能与抑制NF-κB的表达,减轻炎症反应Objective To investigate the effect of oxycodone hydrochloride injection pretreatment on focal cerebral ischemia-reperfusion injury in rats.Methods Seventy-two male SD rats weighing 200-250 g were randomly divided into 3 groups(n=24 each group):sham operation group(sham group),focal cerebral I/R group(I/R group),and oxycodone hydrochloride injection group(Oxy group).Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 h followed by reperfusion.In the Oxy group,oxycodone hydrochloride 0.5 mg/kg was injected iv at 5 min before ischemia.While the same volume of saline(1 mL)was injected in the sham group and I/R group.The neurological deficit score(NDS)was assessed at 24 h of reperfusion,the rats were then sacrificed,and their brains were immediately removed for determination of brain water content and the infarct volume,and the histopathological changes were observed after HE staining.The levels of cytokines(TNF-α,IL-1βand IL-10)in the ischemia cortex were quantified by ELISA.MPO activity in the ischemia cortex was assessed.Western blot was used to detect the expression of NF-κB in the ischemia cortex.The data were analyzed using SPSS 20.0 software,multiple-group comparisons were performed using one-way ANOVA,and LSD-t test was used for pairwise comparison between groups.A P<0.05 was considered statistically significant different.Results Compared with the sham group,NDS,brain water content,relative infarction volume and rate of nerve cell necrosis were significantly increased in the I/R and Oxy groups(all P<0.05).Levels of TNF-α,IL-1β,IL-10,NF-κB and the activities of MPO were increased in the ischemia cortex(all P<0.05).Compared the Oxy group with the I/R group,NDS,brain water content,relative infarction volume and rate of nerve cell necrosis were significantly decreased[(1.7±0.9)vs(2.6±1.1);(79.2±2.4)%vs(84.7±4.2)%;(23.0±5.4)%vs(34.8±6.0)%;(25.2±12.4)%vs(54.8±14.8)%,all P<0.05].The levels of TNF-α,IL-1β,relative expression of NF-κB,and the activities of MPO were significantly d

关 键 词：盐酸羟考酮 局灶 脑 缺血-再灌注 炎症 大鼠 

分 类 号：R614[医药卫生—麻醉学]