右美托咪定对大鼠脓毒症致肝损伤保护作用及可能机制的研究

发布时间：2018-04-22 23:03

本文选题：】右美托咪定 + 脓毒症　；参考：《福建医科大学》2015年硕士论文

【摘要】：【目的】观察不同浓度右美托咪定对脓毒症大鼠炎性因子、鸟氨酸氨基甲酰转移酶(OCT)、STAT3的影响,探讨右美托咪定对脓毒症大鼠肝损伤的保护作用及其可能的机制,为临床治疗脓毒症提供理论依据。【方法】该实验分成两个部分,第一部分:将100只健康SD大鼠随机分为五组(n=20):假手术组(S组)、脓毒症模型组(P组)、右美托咪定2.5μg·kg-1·h-1组(D1组)、右美托咪定5μg·kg-1·h-1组(D2组)、右美托咪定10μg·kg-1·h-1组(D3组)。假手术组仅打开腹腔翻动盲肠,P、D1、D2及D3组采用盲肠结扎及穿孔术(CLP)制备大鼠脓毒症模型诱发肝损伤。D1、D2、D3组在术后0.5h分别尾静脉泵注对应浓度的右美托咪定,药物稀释按5ml·kg-1·h-1,持续时间0.5h,P组与S组于对应时间点泵注等容量的生理盐水。第二部分:根据第一部分的结果,将100只大鼠按随机法分为五组(n=20):假手术组(S组)、脓毒症模型组(P组)、右美托咪定10μg·kg-1·h-1组(D组)、右美托咪定10μg·kg-1·h-1加育亨宾组(DY组)、育亨宾组(Y组)。D组和DY组术后0.5h尾静脉泵注右美托咪定10μg·kg-1·h-1,药物稀释按5ml·kg-1·h-1,持续时间0.5h,S组、P组和Y组于对应时间点泵注等容量的生理盐水;DY组和Y组在建模后,尾静脉注射育亨宾1mg·kg-1,注射持续时间不少于5min。实验两个部分各组分别于术后6、12h放血处死大鼠取其肝脏。应用ELISA检测肝脏IL-6、IL-10及OCT,western blotting检测STAT3,HE染色法观察肝脏损伤病理学情况。【结果】第一部分:与S组同时间比较,P、D1、D2和D3组术后6h、12h肝组织IL-6、IL-10及OCT明显升高,STAT3表达明显上调(P0.05),肝组织有不同程度的病理学损伤;D1、D2、D3组与P组同时间点对比,各项指标均明显下降(P0.05),病理学显示肝组织损伤明显减轻;D1、D2、D3组同时间点比较,各项指标依次下降,病理学检查肝组织损伤也依次减轻,其中D3组各项指标最低(P0.05),肝组织损伤程度最轻。第二部分:与S组同时间比较,P、D、DY和Y组术后6h、12h肝组织IL-6、IL-10及OCT明显升高,STAT3表达明显上调(P0.05),肝组织有不同程度的病理学损伤;D组与P、DY、Y组同时间点相比,IL-6、IL-10及OCT明显下降,STAT3表达明显下调(P0.05);DY组与P、Y组同时间点相比,各项指标浓度降低,STAT3表达下调(P0.05);Y组与P组同时间点相比,各项指标差异无统计学意义(P0.05)。【结论】右美托咪定对脓毒症大鼠肝损伤有保护作用,且具有剂量依赖性,其机制具有α2肾上腺素受体依赖性,下调STAT3可能参与右美托咪定对脓毒症大鼠肝损伤的保护作用。
[Abstract]:[objective] to observe the effects of dexmetomidine at different concentrations on the inflammatory factor, ornithine carbamyltransferase (OCTL) STAT3, in septic rats, and to explore the protective effect and possible mechanism of dexmetomidine on liver injury in septic rats. [methods] the experiment was divided into two parts. Part one: 100 healthy SD rats were randomly divided into five groups: sham operation group (group S), sepsis model group (group P), dexmetomidine 2.5 渭 g kg-1 h-1 group (group D 1), dexmetomidine group (5 渭 g kg-1 h-1 group) and right metomidine group (10 渭 g kg-1 h-1 group). In the sham operation group, the rats with sepsis induced liver injury were induced by cecal ligation and perforation in group D _ 2 and D _ 3. The rats in group D _ 3 were injected with right metomidine at 0.5 h after operation. The drug was diluted according to 5ml kg-1 h-1 for 0.5 h in group P and group S, the same volume of saline was injected by pump at the corresponding time point. Part two: according to the results of part one, #number0# rats were randomly divided into five groups: sham operation group (S group), septic model group (P group), dexmetomidine (10 渭 g kg-1 h-1) group (D group), dexmetomidine 10 渭 g kg-1 h-1 + yohimbine group (DY group), yohimbine group (Y group) and Y group (0.5 h) after operation. Dexmetomidine 10 渭 g kg-1 h-1 was injected by intravenous pump. The drug was diluted as 5ml kg-1 h-1 and lasted 0.5 h. The rats in group S and group Y were injected with saline of equal volume at the corresponding time point. 1mg kg-1 was injected via caudal vein for no less than 5 mins. The liver of each group was harvested at 6h and 12h after operation. The pathological changes of liver injury were observed by ELISA and Octwestern blotting. [results] part one: compared with S group, the expression of IL-6 IL-10 and OCT in liver tissue of group D _ 2 and D _ 3 increased significantly at 6 h after operation. The expression of STAT3 was upregulated. There were different degrees of pathological injury in liver tissue. The same time points were compared between group D _ (1) and D _ (2) D _ (3) and group P (P). All the indexes were significantly decreased (P 0.05). The pathological findings showed that liver tissue injury was significantly reduced in group D _ 1, D _ 2, D _ 2 and D _ 3, and decreased in turn, and liver tissue injury in pathological examination was also reduced in turn, compared with that in group D _ (1) and D _ (2) D _ (2). Among them, group D 3 had the lowest index (P 0.05) and the least degree of liver injury. The second part: compared with the same time in group S and group Y, the expression of IL-6 IL-10 and OCT in liver tissue increased significantly at 12 hours after operation. The expression of STAT3 in liver tissue was significantly up-regulated. The expression of IL-6IL-10 and OCT in group D and group Y were significantly lower than those in group D with different degrees of pathological injury at the same time point. The expression of STAT3 was significantly down-regulated in P0. 05 and DY groups compared with the same time points in P0. 05% P0. 05% DY group. There was no significant difference between the two groups at the same time point. [conclusion] dexmetomidine has a protective effect on liver injury in septic rats, and it is dose-dependent. The mechanism is 伪 2 adrenergic receptor dependent and down-regulation of STAT3 may be involved in the protective effect of dexmetomidine on liver injury in septic rats.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R614

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