右美托咪定对脓毒症大鼠肠黏膜损伤的影响及机制

Effect and mechanism of dexmedetomidine on intestinal mucosa in septic rats

目的探讨右美托咪定(DEX)对脓毒症大鼠肠黏膜损伤的影响及机制。方法选取大鼠40只,随机分为脓毒症组和DEX组,每组各20只,两组用改良盲肠穿刺法(CLP)建立脓毒症模型;另取20只正常新生大鼠作为对照组。三组均采用chiu′s病理评分评估回肠损伤,DEX组在建立CLP模型前15 min腹腔注射40μg/kg的DEX,脓毒症组和对照组均腹腔注射等体积生理盐水。采用ELISA法检测血浆降钙素原(PCT)、C反应蛋白(CRP)水平,West?ern blotting法和免疫组化法分析通路相关蛋白Wnt1、β-catenin和肠道凋亡相关蛋白Bax、Bcl-2、Caspase-3表达。结果对照组、脓毒症组和DEX组的肠黏膜上皮Chui′s评分分别为(0.44±0.25)、(4.54±1.34)、(0.44±0.25)分,PCT水平分别为(261.16±15.23)、(1131.41±100.75)、(825.57±89.13)pg/mL,CRP水平分别为(119.39±14.43)、(842.76±101.27)、(334.10±50.87)ng/mL,Bcl-2蛋白相对表达量分别为0.524±0.009、0.157±0.005、0.305±0.003,Bax蛋白相对表达量分别为0.082±0.008、0.308±0.009、0.218±0.01,Caspase-3蛋白相对表达量分别为0.115±0.009、0.498±0.009、0.325±0.015,Wnt1蛋白相对表达量分别为0.132±0.011、0.496±0.023、0.261±0.006,β-catenin蛋白相对表达量分别为0.103±0.003、0.601±0.020、0.464±0.011,脓毒症组上述指标与对照组与DEX组比较,差异均有统计学意义(P均<0.05)。结论DEX对脓毒血症大鼠损伤肠黏膜组织起到保护作用,其机制可能通过Wnt/β-catenin信号通路调控,使Bcl-2/Bax值趋于正常,Caspase-3水平降低,从而减轻脓毒症期间肠道上皮氧化应激、炎症反应及细胞凋亡。

Objective To investigate the effect of dexmedetomidine(Dex)on intestinal mucosa in neonatal rats with sepsis.Methods Forty rats were randomly divided into the sepsis group and DEX group,with 20 rats in each group.Septic models in the sepsis group and the DEX group were induced with cecal ligation and puncture(CLP).Another 20 normal neonatal rats were selected as the control group,and the ileal injury was evaluated by Chui's scores in all these three groups.The rats in the DEX group were intraperitoneally injected with 40μg/kg DEX at 15 minutes before CLP mod⁃el was established.Rats in the sepsis group and control group were intraperitoneally injected with equal volume of 0.9%NaCl.Plasma levels of procalcitonin(PCT)and C-reactive protein(CRP)were detected by ELISA,and the expression levels of Wnt1,β-catenin,intestinal apoptosis-related proteins Bax,Bcl-2,and Caspase-3 were analyzed by Western blot⁃ting and immunohistochemistry.Results The Chui's scores of intestinal mucosa in the control group,sepsis group and DEX group were(0.44±0.25),(4.54±1.34)and(0.44±0.25)points;the PCT levels were(261.16±15.23),(1131.41±100.75),and(825.57±89.13)pg/mL;the CRP levels were(119.39±14.43),(842.76±101.27),and(334.10±50.87)ng/mL;the expression levels of Bcl-2 were 0.524±0.009,0.157±0.005,and 0.305±0.003;the expression lev⁃els of Bax were 0.082±0.008,0.308±0.009,and 0.218±0.01;the expression levels of Caspase-3 were 0.115±0.009,0.498±0.009,and 0.325±0.015;the expression levels of Wnt1 were 0.132±0.011,0.496±0.023,and 0.261±0.006;the expression levels ofβ-catenin were 0.103±0.003,0.601±0.02,and 0.464±0.011,respectively.Statistically signifi⁃cant differences were found in the above indexes between the control group,the DEX group and the sepsis group(all P<0.05).Conclusions DEX has a protective effect on ileum injury in septic rats,which may normalize the apoptosis-relat⁃ed protein Bcl-2/Bax ratio by regulating the Wnt/β-catenin signaling pathway,thus reducing the oxidative stress,inflam⁃matory response and apoptosis of intestinal epithelium during sepsis.