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右美托咪定对脓毒症急性肺损伤小鼠RAGE的影响

The Influence of Dexmedetomidine about RAGE in Sepsis-induced Acute Lung Injury

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目的 建立盲肠结扎穿孔术(CLP)致小鼠脓毒症急性肺损伤(ALI)模型,观察腹腔注射右美托咪定后小鼠肺部晚期糖基化终末产物受体(RAGE)水平的变化,探讨右美托咪定对脓毒症ALI小鼠RAGE水平的影响.方法 按照随机数表法将60只C57BL/6雄性小鼠分为4组,分别为假手术组(Sham组)、假手术+右美托咪定组(Sham+DEX组)、CLP组、CLP+DEX组,每组15只.CLP组和CLP+DEX组小鼠均行CLP建立脓毒症ALI模型,而Sham组和Sham+DEX组小鼠只行开关腹操作.造模成功后30 min,Sham+DEX组和CLP+DEX组小鼠通过腹腔注射右美托咪定50 μg/kg,其余组小鼠在相同部位注射等体积0.9%的氯化钠溶液.各组于造模后24 h,测定小鼠肺组织湿干重比(W/D),观察此时小鼠肺组织的病理改变,并检测各组小鼠支气管肺泡灌洗液中RAGE、S100A12、IL-6及HMGB1的水平情况,以及测定肺组织中RAGE蛋白的表达.结果 (1)肺湿干重比:与Sham组相比,CLP组和CLP+DEX组在造模后24 h的肺组织W/D显著增加,与CLP组相比,CLP+DEX组有明显降低,但仍高于Sham组;(2)HE染色结果:Sham组小鼠未出现肺损伤,Sham和Sham+DEX组小鼠于假手术后24 h的HE染色结果无明显差异,而CLP组小鼠肺结构组织学发生显著改变,广泛肺出血,炎症细胞浸润增加.通过右美托咪定治疗后,CLP+DEX组肺损伤的严重程度显著改善,但仍较Sham组严重;(3)Smith评分:与Sham组相比,CLP组和CLP+DEX组在造模后24 h的Smith评分显著增加,与CLP组相比,CLP+DEX组有明显降低,但仍高于Sham组;(4)炎症因子水平:与Sham组相比,CLP组和CLP+DEX组在造模后24 h的RAGE、S100A12、HMGB1、IL-6水平显著增加,与CLP组相比,CLP+DEX组有明显降低,但仍高于Sham组;(5)RAGE蛋白表达水平:与Sham组相比,CLP组和CLP+DEX组在造模后24 h的肺组织中的RAGE蛋白表达水平显著增加,与CLP组相比,CLP+DEX组有明显降低,但仍高于Sham组.Sham组和Sham+DEX组各项指标差异无统计学意义(P>0.05).结论 右美托咪定可有效降低脓毒症后支气管肺泡灌洗液中的RAGE、S100A12、HMGB1、IL-6水平,另外,还降低了肺组织中的RAGE蛋白的表达水平,使脓毒症ALI小鼠的肺组织水肿情况和损伤程度得到改善.
Objective Establish a mouse model of acute lung injury(ALI)induced by cecal ligation and perforation(CLP),observe the changes in receptor for advanced glycation end products(RAGE)levels in the lungs of mice after intraperitoneal injection of dexmedetomidine,and explore the effect of dexmedetomidine on RAGE in ALI mice with sepsis.Methods According to the random number table method,A total of 60 C57BL/6 male mice were divided into 4 groups,including Sham operation group(Sham group),Sham operation+dexmedetomidine group(Sham+DEX group),sepsis group(CLP group),sepsis+dexmedetomidine group(CLP+DEX group),with 15 mice in each group.CLP and CLP+DEX mice were treated with CLP to make sepsis ALI models,while mice in Sham group and Sham+DEX group were only given the switch abdominal op-eration.Thirty min after successful modeling,mice in the Sham+DEX group and CLP+DEX group were in-traperitoneally injected with dexmedetomidine(50 μg/kg),and the mice in the other groups were injected with an equal volume of 0.9%sodium chloride solution at the same site.The wet-dry weight ratio of the mouse lung tissue was measured 24h after modeling,and the pathological changes of the mouse lung tissue were ob-served,and the levels of HMGB1,IL-6,S100A12 and RAGE in the bronchoalveolar lavage fluid in the serum of the mice in each group were detected,and the expression of REGE protein in the lung tissue was measured.Results(1)HE staining results:There was no lung injury in the Sham group mice,and there was no signifi-cant difference in HE staining results between the Sham and Sham+DEX groups mice 24h after sham surgery.However,significant histological changes occurred in the lung structure of the CLP group mice,with extensive pulmonary hemorrhage and increased infiltration of inflammatory cells.After treatment with dexmedetomidine,the severity of lung injury in the CLP+DEX group significantly improved,but remained more severe than in the Sham group;(2)Smith score:Compared with the Sham group,the CLP group and CLP+DEX group showed a significant increase in Smith score 24h after modeling.Compared with the CLP group,the CLP+DEX group showed a significant decrease,but higher than the Sham group;(3)Lung wet to dry weight ratio(W/D):Com-pared with the Sham group,the CLP group and CLP+DEX group showed a significant increase in lung tissue W/D 24h after modeling.Compared with the CLP group,the CLP+DEX group showed a significant decrease,but higher than the Sham group;(4)Inflammatory cytokine levels:Compared with the Sham group,the levels of RAGE,S100A12,HMGB1,and IL-6 in the CLP group and CLP+DEX group significantly increased 24 h after modeling.Compared with the CLP group,the CLP+DEX group showed a significant decrease,but higher than the Sham group;(5)RAGE protein expression levels:Compared with the Sham group,the CLP group and CLP+DEX group showed a significant increase in RAGE protein expression levels in lung tissue 24 h after mod-eling.Compared with the CLP group,the CLP+DEX group showed a significant decrease,but higher than the Sham group.There was no significant difference in various indicators between the Sham group and the Sham+DEX group.Conclusions Dexmedetomidine can effectively reduce the levels of RAGE,S100A12,HMGB1 and IL-6 in bronchoalveolar lavage fluid after sepsis,and also reduce the expression level of RAGE protein in lung tissue,so that the edema and degree of lung tissue in mice with acute lung injury of sepsis can be improved.

sepsisacute respiratory distress syndromereceptor for advanced glycation end productsdexmedetomidine

王燕燕、刘志慧、李淑凡、王娇娇、张子怡、张存宇、曹若男

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包头医学院中心临床医学院,内蒙古包头 014040

包头市中心医院麻醉科,内蒙古包头 014040

内蒙古医科大学中心临床学院,内蒙古呼和浩特 010050

脓毒症 急性肺损伤 晚期糖基化终末产物受体 右美托咪定

包头医学院研究生科研创新项目内蒙古医科大学联合项目

bycx2023016YKD2021LH063

2024

内蒙古医学杂志
内蒙古自治区医学会

内蒙古医学杂志

影响因子:0.537
ISSN:1004-0951
年,卷(期):2024.56(4)