右旋美托咪啶在脓毒血症继发性肺损伤中的作用及可能机制
发布时间：2018-12-31 17:27
【摘要】：目的观察右旋美托咪啶(DEX)预处理对不同发展阶段的败血症的影响及其可能机制。 实验方法采用忙肠结扎穿孔法建立败血症模型,149只SD大鼠随机分配入空白对照组22只(无任何处理)、假手术组22只(剖腹探查和肠系膜血管盲肠支分离并放置引流条)、手术组35只(剖腹探查后肠系膜血管盲肠支分离,盲肠结扎穿孔术后放置引流条)、右旋美托咪啶预处理组35只(麻醉10min后腹腔注射右美lOug/kg,之后手术处理)、及阿替美唑拮抗组35只(麻醉时腹腔注射阿替美唑250ug/kg,之后处理同右美组),并观察术后24h内存活率、测量肛温、疾病严重程度评分(空白和假手术组各10只,其余组各15只),并于术后4h、8h、12h、24h处死大鼠(空白和假手术组每个时间点3只,其余组5只),取左室血测血气,取肺组织行HE染色做病理评分,及肺小窝蛋白westernblot法分析其随疾病进展的表达变化。统计学处理采用SPSS22.0软件,所有测量值用均数±标准差(M±SD)表示,体温及疾病严重程度评分组内比较采用复合效应线性模型分析,组间比较采用完全随机设计多个组两两比较(LSD)方差分析。方差一致性检验采用Levene或Bartlet's检验。组间生存率资料用log-rank口2检验,生存曲线用Kaplan Meier分析。差异显著性水平设为双尾a=0.05。 结果 (1)右美预处理能显著提高败血症大鼠24小时存活率(40%vs.C组20%,P0.05),阿替美唑(AMZ)对DEX的这一保护作用无显著拮抗(46.7%,P0.05,vs. CD)。 (2)右美预处理能显著抑制败血症引起的体温升高、肺部病理改变(P0.05, vs. C),未显著改善疾病症状评分(P0.05, vs. C);阿替美唑显著拮抗其抗炎性细胞浸润作用(P0.05, vs.CD),改善肺部水肿(P0.05,vs.CD),提高疾病症状评分(P0.05,vs.CD)。 (3)败血症能显著影响小窝蛋白表达规律并下调其表达(P0.05,vs.S/CT),右美预处理能抑制败血症引起的表达规律改变(P0.05,vs. C)并上调其表达(P0.05,vs.C),阿替美唑显著拮抗右美上调小窝蛋白的作用(P0.05,vs. CD),但并未抑制其对小窝蛋白表达规律的保护作用。 结论右美预处理能显著降低脓毒血症的死亡率和肺损伤,这可能部分通过激活α2肾上腺素受体和咪唑林受体维持小窝蛋白的表达起作用。
[Abstract]:Objective to observe the effect of dexmetidine (DEX) preconditioning on septicemia in different stages and its possible mechanism. Methods the septicemia model was established by busy intestinal ligation and perforation. 149 SD rats were randomly assigned to the blank control group (22 rats without any treatment) and the sham operation group (22 rats underwent laparotomy and mesenteric caecum branch separation and placed drainage strips). 35 rats in operation group were treated with caecum branches of mesenteric vessels after laparotomy, drainage strips were placed after cecal ligation and perforation, and 35 rats in dexmetidine preconditioning group (after intraperitoneal injection of dexamethasone after anaesthesia 10min). And altimezole antagonist group (35 rats were treated with altimetrazole 250 g / kg intraperitoneally during anesthesia and treated with the same right side group), and the survival rate, anal temperature and disease severity score were observed within 24 hours after operation (10 rats in blank group and 10 in sham operation group). 15 rats in each group were killed at 4 h, 8 h, 12 h and 24 h after operation (3 rats in blank and sham-operation group and 5 rats in other group). Blood gas was measured in left ventricular blood and HE staining was performed in lung tissue for pathological evaluation. And lung fossa protein westernblot method was used to analyze the expression of lung fossa protein with disease progression. SPSS22.0 software was used for statistical analysis, all measurements were expressed by mean 卤standard deviation (M 卤SD). The body temperature and disease severity score group were compared by compound effect linear model analysis. (LSD) ANOVA was used to compare two groups of groups with complete random design. Variance consistency test was performed by Levene or Bartlet's test. The survival rate was examined by log-rank 's mouth 2 test and the survival curve was analyzed by Kaplan Meier. The significant level of the difference was 0. 05. Results (1) the 24 hour survival rate of septicemia rats was significantly increased by dexamethasone preconditioning (40%vs.C group 20: P0.05), but the protective effect of altimezole (AMZ) on DEX was not significantly antagonized (46.7% P 0.05). Vs. CD). (2) dexamethasone pretreatment could significantly inhibit the hyperthermia induced by septicemia and pulmonary pathological changes (P0.05, vs. C), did not significantly improve the symptom score (P0.05, vs. C);). Altimezole significantly antagonized its anti-inflammatory cell infiltration (P0.05, vs.CD), improved pulmonary edema (P0.05vs.CD) and increased the disease symptom score (P0.05vs.CD). (3) septicemia could significantly affect the expression of fossa protein and down-regulate its expression (P0.05vs.SrCT). Right preconditioning could inhibit the change of expression pattern (P0.05V 路C) and up-regulate its expression (P0.05). Vs.C, Atemezole significantly antagonized the up-regulation of fossa protein (P0.05V 路CD), but did not inhibit its protective effect on the expression of fossa protein. Conclusion dexamethasone preconditioning can significantly reduce mortality and lung injury of sepsis, which may partly play a role by activating 伪 2-adrenoceptor and midazoline receptor to maintain the expression of fossa protein.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614
本文编号：2396888
[Abstract]:Objective to observe the effect of dexmetidine (DEX) preconditioning on septicemia in different stages and its possible mechanism. Methods the septicemia model was established by busy intestinal ligation and perforation. 149 SD rats were randomly assigned to the blank control group (22 rats without any treatment) and the sham operation group (22 rats underwent laparotomy and mesenteric caecum branch separation and placed drainage strips). 35 rats in operation group were treated with caecum branches of mesenteric vessels after laparotomy, drainage strips were placed after cecal ligation and perforation, and 35 rats in dexmetidine preconditioning group (after intraperitoneal injection of dexamethasone after anaesthesia 10min). And altimezole antagonist group (35 rats were treated with altimetrazole 250 g / kg intraperitoneally during anesthesia and treated with the same right side group), and the survival rate, anal temperature and disease severity score were observed within 24 hours after operation (10 rats in blank group and 10 in sham operation group). 15 rats in each group were killed at 4 h, 8 h, 12 h and 24 h after operation (3 rats in blank and sham-operation group and 5 rats in other group). Blood gas was measured in left ventricular blood and HE staining was performed in lung tissue for pathological evaluation. And lung fossa protein westernblot method was used to analyze the expression of lung fossa protein with disease progression. SPSS22.0 software was used for statistical analysis, all measurements were expressed by mean 卤standard deviation (M 卤SD). The body temperature and disease severity score group were compared by compound effect linear model analysis. (LSD) ANOVA was used to compare two groups of groups with complete random design. Variance consistency test was performed by Levene or Bartlet's test. The survival rate was examined by log-rank 's mouth 2 test and the survival curve was analyzed by Kaplan Meier. The significant level of the difference was 0. 05. Results (1) the 24 hour survival rate of septicemia rats was significantly increased by dexamethasone preconditioning (40%vs.C group 20: P0.05), but the protective effect of altimezole (AMZ) on DEX was not significantly antagonized (46.7% P 0.05). Vs. CD). (2) dexamethasone pretreatment could significantly inhibit the hyperthermia induced by septicemia and pulmonary pathological changes (P0.05, vs. C), did not significantly improve the symptom score (P0.05, vs. C);). Altimezole significantly antagonized its anti-inflammatory cell infiltration (P0.05, vs.CD), improved pulmonary edema (P0.05vs.CD) and increased the disease symptom score (P0.05vs.CD). (3) septicemia could significantly affect the expression of fossa protein and down-regulate its expression (P0.05vs.SrCT). Right preconditioning could inhibit the change of expression pattern (P0.05V 路C) and up-regulate its expression (P0.05). Vs.C, Atemezole significantly antagonized the up-regulation of fossa protein (P0.05V 路CD), but did not inhibit its protective effect on the expression of fossa protein. Conclusion dexamethasone preconditioning can significantly reduce mortality and lung injury of sepsis, which may partly play a role by activating 伪 2-adrenoceptor and midazoline receptor to maintain the expression of fossa protein.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614
【参考文献】
相关期刊论文 前1条
1 农丽丹;邓春玉;邝素娟;张光燕;崔建修;;右美托咪定抑制五羟色胺诱导的人离体肺内小动脉收缩[J];南方医科大学学报;2014年03期
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