作者：刘铁军1 ，董晓柳 2 ，张树波 1 ，赵晓晶 1 ，段立昆 3 ，李红霞 4

单位：

1.063000 河北省唐山市，华北理工大学附属医院麻醉科　；2.063001 河北省唐山市人民医院神经内科　；3.063108 河北省唐山市，开滦总医院南范各庄医院 4.064400 河北省迁安市人民医院麻醉科；通信作者：刘铁军，E-mail：28710694@qq.com

关键词：

脓毒症；大鼠；右美托咪定；认知障碍；Shh 信号通路

Keywords：

Sepsis；Rats；Dexmedetomidine；Cognition disorders；Shh signaling pathway

CLC：

R 631

DOI：

DOI：10.3969/j.issn.1008-5971.2020.04.017

Funds：

河北省科技厅重点课题（17277759D）；河北省医学科学研究课题计划（20191109）；河北省高等学校科学研究项目（QN2019199）；唐山市科学技术研究与发展计划（19150215E）

摘要：

背景　右美托咪定可透过血 - 脑脊液屏障并对脓毒症大鼠具有一定保护作用，但目前关于其对脓毒症所致认知障碍改善效果的研究报道较少见。目的　探讨右美托咪定对老年脓毒症大鼠 Shh 信号通路及认知功能的影响。方法　2019 年 1—9 月，选取健康雄性 SD 大鼠 54 只，采用随机数字表法分为 Sham 组、CLP 组、Dex 组，每组 18 只。Sham 组大鼠仅行剖腹探查术，CLP 组大鼠采用盲肠结扎穿孔法制备脓毒症模型，Dex 组大鼠于脓毒症模型制备后 6 h腹腔注射右美托咪定。比较三组大鼠给药后逃避潜伏期，穿越平台次数，处于平台所在象限时间，脑组织含水量，海马组织 Shh、Gli-1、Ptc 含量及 ZO-1、Claudin-5 相对表达量。结果　与 Sham 组比较，CLP 组、Dex 组大鼠给药后逃避潜伏期延长，穿越平台次数减少，处于平台所在象限时间缩短（P<0.05）；与 CLP 组比较，Dex 组大鼠给药后逃避潜伏期缩短，穿越平台次数增多，处于平台所在象限时间长（P<0.05）。与 Sham 组比较，CLP 组、Dex 组大鼠给药后脑组织含水量增多（P<0.05）；与 CLP 组比较，Dex 组大鼠给药后脑组织含水量少（P<0.05）。与 Sham 组比较，CLP 组、Dex 组大鼠给药后海马组织 Shh、Gli-1 含量降低，Ptc 含量升高（P<0.05）；与 CLP 组比较，Dex 组大鼠给药后海马组织 Shh、Gli-1 含量升高，Ptc 含量降低（P<0.05）。（4）与 Sham 组比较，CLP 组、Dex 组大鼠给药后海马组织 ZO-1、Claudin-5 相对表达量降低（P<0.05）；与 CLP 组比较，Dex 组大鼠给药后 24 h 海马组织 ZO-1、Claudin-5 蛋白相对表达量升高（P<0.05）。结论　右美托咪定可有效改善老年脓毒症大鼠认知功能，降低血 - 脑脊液屏障通透性，其作用机制可能与激活 Shh 信号通路有关。

Abstract：

Background　Dexmedetomidine is can penetrate the blood-cerebrospinal fluid barrier，which hasprotective effect in rats with sepsis to some extent，however there are few reports about its improvement effect on cognitivedisorder caused by sepsis so far. Objective　To investigate the influence of dexmedetomidine on Shh signaling pathway andcognitive function in aged rats with sepsis. Methods　From January to September 2019，54 healthy male SD rats were selectedand then divided into Sham group，CLP group and Dex group according to random number table method，with 18 rats in eachgroup. Rats in Sham group received exploratory laparotomy only，rats in CLP group were prepared for sepsis model by cecalligation and puncture，while rats in Dex group received intraperitoneal injection of dexmedetomidine 6 hours after preparationof sepsis model. Escape incubation period，times of crossing platform，duration of keeping platform quadrant，brain watercontent，contents of Shh，Gli-1 and Ptc as well as relative protein expression quantity of ZO-1 and Claudin-5 in hippocampuswere compared in the three groups after medication. Results　Compared with those in Sham group，CLP group and Dex groupshowed statistically significantly longer escape incubation period，less times of crossing platform and shorter duration of keepingplatform quadrant after medication（P<0.05）；compared with those in CLP group，Dex group showed statistically significantlyshorter escape incubation period，more times of crossing platform and longer duration of keeping platform quadrant aftermedication（P<0.05）.Brain water content in CLP group and Dex group was statistically significantly more than that in Shamgroup after medication，respectively，while brain water content in Dex group was statistically significantly less than that in CLPgroup（P<0.05）.Compared with those in Sham group，CLP group and Dex group showed lower contents of Shh and Gli-1 buthigher Ptc content in hippocampus after medication（P<0.05）；compared with those in CLP group，Dex group showed highercontents of Shh and Gli-1 but lower Ptc content in hippocampus after medication（P<0.05）.Relative protein expression quantityof ZO-1 and Claudin-5 in hippocampus in CLP group and Dex group was statistically significantly lower than that in Sham groupafter medication，respectively，while relative protein expression quantity of ZO-1 and Claudin-5 in hippocampus in Dex groupwas statistically significantly higher than that in CLP group，respectively（P<0.05）. Conclusion　Dexmedetomidine caneffectively improve cognitive function and reduce the permeability of blood-cerebrospinal fluid barrier，the action mechanism ispossibly correlated with the activation of Shh signaling pathway.

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