腹腔注射右美托咪定对大鼠腹腔粘连的影响及胆碱能抗炎通路在其中的作用

Effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway

目的评价腹腔注射右美托咪定对大鼠腹腔粘连的影响及胆碱能抗炎通路在其中的作用。方法清洁级健康成年雄性SD大鼠40只,体重220~250 g,采用随机数字表法分为4组(n=10):假手术组(Sham组)、腹腔粘连组(AA组)、右美托咪定组(DEX组)和右美托咪定+甲基牛扁碱组(DEX-M组)。采用盲肠摩擦法建立大鼠腹腔粘连模型。Sham组仅打开腹腔后缝合;AA组分别于腹腔和尾静脉注射生理盐水2 ml;DEX组和DEX-M组分别尾静脉注射生理盐水2 ml和α7烟碱型乙酰胆碱受体拮抗剂甲基牛扁碱2.4μg/g(溶于2 ml生理盐水中),同时腹腔注射右美托咪定10μg/kg(溶于2 ml生理盐水中)。建模后7 d时,麻醉下打开腹部切口,观察腹腔粘连形成情况,并采用Phillips法进行评分;采用ELISA检测腹水转化生长因子-β1(TGF-β1)和血清TNF-α的浓度。然后处死大鼠,取盲肠组织及其对侧腹膜及粘连纤维带,光镜下观察病理学结果。结果与Sham组相比,AA组和DEX-M组腹部粘连评分升高,血清TNF-α浓度升高,AA组、DEX组和DEX-M组腹水TGF-β1浓度升高(P<0.05);与AA组相比,DEX-M组血清TNF-α和腹水TGF-β1的浓度降低,DEX组腹部粘连评分降低(P<0.05),DEX组盲肠组织、腹膜及粘连纤维带病理学损伤减轻;与DEX-M组相比,DEX组血清TNF-α浓度升高(P<0.05),腹水TGF-β1浓度差异无统计学意义(P>0.05),盲肠组织、腹膜及粘连纤维带病理学损伤加重。结论腹腔注射右美托咪定可减轻大鼠腹腔粘连,其机制与激活胆碱能抗炎通路,减轻全身炎症反应有关。

Objective To evaluate the effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway.Methods Forty clean-grade healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 4 groups(n=10 each)using a random number table method:sham operation group(Sham group),abdominal adhesion group(AA group),dexmedetomidine group(DEX group)and dexmedetomidine plus methyllycaconitine group(DEX-M group).The rat model of abdominal adhesions was established by cecal friction method.In Sham group,abdominal cavity was only opened and then sutured.Normal saline 2 ml was injected into the abdominal cavity and tail vein in group AA.In DEX and DEX-M groups,normal saline 2 ml andα7 nicotinic acetylcholine receptor antagonist methyllycaconitine 2.4μg/g(dissolved in 2 ml normal saline)were injected,respectively,and dexmedetomidine 10μg/kg(dissolved in 2 ml normal saline)was intraperitoneally injected at the same time.The abdominal incision was opened under anesthesia at 7 days after establishing the model to observe the formation of abdominal adhesion,Phillips method was used for scoring,and enzyme-linked immunosorbent assay was used to determine the transforming growth factor-beta1(TGF-β1)concentrations in ascites and tumor necrosis factor-alpha(TNF-α)concentrations in serum.The rats were then sacrificed,and the caecum tissue and its contralateral peritoneum and adhesion fibrous strips were obtained for examination of the pathological changes with a light microscope.Results Compared with group Sham,the abdominal adhesion score and serum TNF-αconcentrations were significantly increased in AA and DEX-M groups,and the TGF-β1 concentration in ascites was significantly increased in AA,DEX and DEX-M groups(P<0.05).Compared with group AA,the serum TNF-αconcentrations and TGF-β1 concentration in ascites were significantly decreased in group DEX-M,and the abdominal adhesion score was significantly decreased(P<0.05),and the pathological changes of caecum tissue,contralateral peritoneum and adhesion fibrous strips were significantly attenuated in group DEX.Compared with group DEX-M,the serum TNF-αconcentrations were significantly increased(P<0.05),no significant change was found in TGF-β1 concentration in ascites(P>0.05),and the pathological changes of caecum tissue,contralateral peritoneum and adhesion fibrous strips were accentuated in group DEX.Conclusion Intraperitoneally injected dexmedetomidine can mitigate abdominal adhesions,and the mechanism is related to activating cholinergic anti-inflammatory pathway and reducing systemic inflammatory response in rats.