右美托咪定对脓毒症大鼠肠道损伤的保护效应
发布时间：2018-11-17 13:11
【摘要】：目的:探讨右美托咪定(DEX)是否可以通过抑制炎症反应改善脓毒症大鼠的肠道损伤。方法:雄性SD大鼠随机分为4组(n=16),假手术组(Sham)、模型组(CLP)、DEX治疗组(DEX)、DEX复合育亨宾(YOH)组(DEX+YOH)。CLP组、DEX组、DEX+YOH组大鼠均建立盲肠结扎与穿孔(CLP)模型,Sham组大鼠只游离盲肠不做穿孔结扎。DEX组大鼠于术后0.5h沿尾静脉泵注DEX 5μg·kg-1·h-1,持续时间为1h;DEX+YOH组在泵注相同剂量DEX前静注YOH 1mg/kg;Sham组、CLP组泵注等量生理盐水。各组分别于术后12h、24h随机留取8只大鼠血清和小肠组织,应用光学显微镜观察小肠组织病理学改变;分光光度法检测血清二胺氧化酶(DAO)及D-乳酸(D-lactate)表达水平;酶联免疫吸附试验(ELISA)检测血清及小肠组织TNF-α、IL-1β、IL-6表达水平;蛋白印迹法(WB)检测小肠组织闭合蛋白(Occludin)、TLR4的相对表达水平。用于观察生存率的40只大鼠同样按上述方法分为4组(n=10),观察各组大鼠术后的一般情况,记录7天内的死亡率。结果:(1)与Sham组同时间点相比,CLP、DEX、DEX+YOH组小肠组织病理学损伤明显,DAO、D-lactate表达水平明显上升,Occludin表达下降,TNF-α、IL-1β、IL-6、TLR4表达上升(P0.05)。与CLP组同时间点相比,DEX、DEX+YOH组小肠组织病理学损伤明显减轻,DAO、D-lactate表达水平显著下降,Occludin表达上升,TNF-α、IL-1β、IL-6、TLR4水平下降(P0.05),其中DEX+YOH组大鼠小肠组织12h的TNF-α与24h的IL-1β表达水平与CLP组相比差异无统计学意义(P0.05)。与DEX组同时间点相比,DEX+YOH组小肠组织损伤明显,DAO、D-lactate水平上升,Occludin表达下降,TNF-α、IL-1β、IL-6、TLR4水平上升(P0.05)。(2)与Sham组相比,CLP组、DEX+YOH组大鼠死亡率明显上升(P0.05),DEX组死亡率上升不明显(P0.05);与CLP组相比,DEX组大鼠死亡率有所下降(P0.05),DEX+YOH组死亡率下降不明显(P0.05);与DEX组相比,DEX+YOH组大鼠死亡率上升。结论:右美托咪定能明显降低脓毒症大鼠的肠道损伤,其机制可能与通过α2受体抑制炎症反应有关。
[Abstract]:Aim: to investigate whether dexmetomidine (DEX) can ameliorate intestinal injury in septic rats by inhibiting inflammatory response. Methods: male SD rats were randomly divided into 4 groups: sham operation group, (Sham), model group, (CLP), DEX treatment group, (DEX), DEX combined with yohimbine (YOH) (DEX YOH). CLP group, DEX group. The (CLP) model of cecal ligation and perforation was established in DEX YOH group, the free caecum was not ligated by free cecum in Sham group, and DEX 5 渭 g kg-1 h-1 was injected into the caudal vein of DEX rats at 0.5 h after operation for 1 h. In DEX YOH group, 1 mg / kg YOH was injected intravenously before the same dose of DEX, and the same amount of normal saline was injected into CLP group. The serum and small intestine tissues of 8 rats were randomly selected at 12 hours and 24 hours after operation. The histopathological changes of small intestine were observed by optical microscope, and the levels of serum diamine oxidase (DAO) and D-lactic acid (D-lactate) were detected by spectrophotometry. Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of TNF- 伪, IL-1 尾 and IL-6 in serum and small intestine, and (WB) was used to detect the relative expression of (Occludin), TLR4. The 40 rats who were used to observe the survival rate were also divided into 4 groups (n = 10) according to the above method. The general situation of the rats in each group was observed and the mortality within 7 days was recorded. Results: (1) compared with Sham group, the histopathological injury of small intestine in CLP,DEX,DEX YOH group was obvious, the expression of DAO,D-lactate was increased, the expression of Occludin was decreased, and the expression of TNF- 伪, IL-1 尾, IL-6, was decreased in CLP,DEX,DEX YOH group. The expression of TLR4 increased (P0.05). Compared with CLP group at the same time point, the histopathological damage of small intestine in DEX,DEX YOH group was significantly alleviated, the expression of DAO,D-lactate decreased significantly, the expression of Occludin increased, and the levels of TNF- 伪, IL-1 尾 and IL-6,TLR4 decreased (P0.05). There was no significant difference in the expression of TNF- 伪 and IL-1 尾 between DEX YOH group and CLP group at 12 h and 24 h (P0.05). Compared with DEX group at the same time point, the small intestine tissue damage was obvious, DAO,D-lactate level was increased, Occludin expression was decreased, TNF- 伪, IL-1 尾, IL-6,TLR4 levels were increased in, DEX YOH group (P0.05). (2) compared with Sham group, CLP group. The mortality of rats in DEX YOH group was significantly increased (P0.05), DEX group mortality was not significantly increased (P0.05); Compared with CLP group, the mortality of DEX group decreased (P0.05), DEX YOH group did not decrease significantly (P0.05); compared with DEX group, DEX YOH group rat mortality increased. Conclusion: dexmetomidine can significantly reduce intestinal injury in septic rats, and its mechanism may be related to the inhibition of inflammation through 伪 2 receptor.
【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
[Abstract]:Aim: to investigate whether dexmetomidine (DEX) can ameliorate intestinal injury in septic rats by inhibiting inflammatory response. Methods: male SD rats were randomly divided into 4 groups: sham operation group, (Sham), model group, (CLP), DEX treatment group, (DEX), DEX combined with yohimbine (YOH) (DEX YOH). CLP group, DEX group. The (CLP) model of cecal ligation and perforation was established in DEX YOH group, the free caecum was not ligated by free cecum in Sham group, and DEX 5 渭 g kg-1 h-1 was injected into the caudal vein of DEX rats at 0.5 h after operation for 1 h. In DEX YOH group, 1 mg / kg YOH was injected intravenously before the same dose of DEX, and the same amount of normal saline was injected into CLP group. The serum and small intestine tissues of 8 rats were randomly selected at 12 hours and 24 hours after operation. The histopathological changes of small intestine were observed by optical microscope, and the levels of serum diamine oxidase (DAO) and D-lactic acid (D-lactate) were detected by spectrophotometry. Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of TNF- 伪, IL-1 尾 and IL-6 in serum and small intestine, and (WB) was used to detect the relative expression of (Occludin), TLR4. The 40 rats who were used to observe the survival rate were also divided into 4 groups (n = 10) according to the above method. The general situation of the rats in each group was observed and the mortality within 7 days was recorded. Results: (1) compared with Sham group, the histopathological injury of small intestine in CLP,DEX,DEX YOH group was obvious, the expression of DAO,D-lactate was increased, the expression of Occludin was decreased, and the expression of TNF- 伪, IL-1 尾, IL-6, was decreased in CLP,DEX,DEX YOH group. The expression of TLR4 increased (P0.05). Compared with CLP group at the same time point, the histopathological damage of small intestine in DEX,DEX YOH group was significantly alleviated, the expression of DAO,D-lactate decreased significantly, the expression of Occludin increased, and the levels of TNF- 伪, IL-1 尾 and IL-6,TLR4 decreased (P0.05). There was no significant difference in the expression of TNF- 伪 and IL-1 尾 between DEX YOH group and CLP group at 12 h and 24 h (P0.05). Compared with DEX group at the same time point, the small intestine tissue damage was obvious, DAO,D-lactate level was increased, Occludin expression was decreased, TNF- 伪, IL-1 尾, IL-6,TLR4 levels were increased in, DEX YOH group (P0.05). (2) compared with Sham group, CLP group. The mortality of rats in DEX YOH group was significantly increased (P0.05), DEX group mortality was not significantly increased (P0.05); Compared with CLP group, the mortality of DEX group decreased (P0.05), DEX YOH group did not decrease significantly (P0.05); compared with DEX group, DEX YOH group rat mortality increased. Conclusion: dexmetomidine can significantly reduce intestinal injury in septic rats, and its mechanism may be related to the inhibition of inflammation through 伪 2 receptor.
【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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