【摘要】：目的:探討右美托咪定(DEX)是否可以通過(guò)抑制炎癥反應(yīng)改善膿毒癥大鼠的腸道損傷。方法:雄性SD大鼠隨機(jī)分為4組(n=16),假手術(shù)組(Sham)、模型組(CLP)、DEX治療組(DEX)、DEX復(fù)合育亨賓(YOH)組(DEX+YOH)。CLP組、DEX組、DEX+YOH組大鼠均建立盲腸結(jié)扎與穿孔(CLP)模型,Sham組大鼠只游離盲腸不做穿孔結(jié)扎。DEX組大鼠于術(shù)后0.5h沿尾靜脈泵注DEX 5μg·kg-1·h-1,持續(xù)時(shí)間為1h;DEX+YOH組在泵注相同劑量DEX前靜注YOH 1mg/kg;Sham組、CLP組泵注等量生理鹽水。各組分別于術(shù)后12h、24h隨機(jī)留取8只大鼠血清和小腸組織,應(yīng)用光學(xué)顯微鏡觀察小腸組織病理學(xué)改變;分光光度法檢測(cè)血清二胺氧化酶(DAO)及D-乳酸(D-lactate)表達(dá)水平;酶聯(lián)免疫吸附試驗(yàn)(ELISA)檢測(cè)血清及小腸組織TNF-α、IL-1β、IL-6表達(dá)水平;蛋白印跡法(WB)檢測(cè)小腸組織閉合蛋白(Occludin)、TLR4的相對(duì)表達(dá)水平。用于觀察生存率的40只大鼠同樣按上述方法分為4組(n=10),觀察各組大鼠術(shù)后的一般情況,記錄7天內(nèi)的死亡率。結(jié)果:(1)與Sham組同時(shí)間點(diǎn)相比,CLP、DEX、DEX+YOH組小腸組織病理學(xué)損傷明顯,DAO、D-lactate表達(dá)水平明顯上升,Occludin表達(dá)下降,TNF-α、IL-1β、IL-6、TLR4表達(dá)上升(P0.05)。與CLP組同時(shí)間點(diǎn)相比,DEX、DEX+YOH組小腸組織病理學(xué)損傷明顯減輕,DAO、D-lactate表達(dá)水平顯著下降,Occludin表達(dá)上升,TNF-α、IL-1β、IL-6、TLR4水平下降(P0.05),其中DEX+YOH組大鼠小腸組織12h的TNF-α與24h的IL-1β表達(dá)水平與CLP組相比差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。與DEX組同時(shí)間點(diǎn)相比,DEX+YOH組小腸組織損傷明顯,DAO、D-lactate水平上升,Occludin表達(dá)下降,TNF-α、IL-1β、IL-6、TLR4水平上升(P0.05)。(2)與Sham組相比,CLP組、DEX+YOH組大鼠死亡率明顯上升(P0.05),DEX組死亡率上升不明顯(P0.05);與CLP組相比,DEX組大鼠死亡率有所下降(P0.05),DEX+YOH組死亡率下降不明顯(P0.05);與DEX組相比,DEX+YOH組大鼠死亡率上升。結(jié)論:右美托咪定能明顯降低膿毒癥大鼠的腸道損傷,其機(jī)制可能與通過(guò)α2受體抑制炎癥反應(yīng)有關(guān)。
[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- 偽, 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- 偽, 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- 偽, IL-1 尾 and IL-6,TLR4 decreased (P0.05). There was no significant difference in the expression of TNF- 偽 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- 偽, 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 偽 2 receptor.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R614

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