右美托咪定联合亚低温处理对脓毒症模型大鼠肺组织中HMGB1、TLR4及Trem-1水平的影响
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篇名: 右美托咪定联合亚低温处理对脓毒症模型大鼠肺组织中HMGB1、TLR4及Trem-1水平的影响
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摘要: 目的:探讨右美托咪定联合亚低温处理对脓毒症模型大鼠肺组织中高迁移率族蛋白B1(HMGB1)、Toll样受体4(TLR4)及髓样细胞触发受体1(Trem-1)水平的影响。方法:采用随机数字表法将100只SD大鼠分为假手术组(生理盐水)、模型组(生理盐水)、右美托咪定组(2 μg/kg)、亚低温组(生理盐水+全身喷洒凉水致肛温32~35 ℃)和联合组(右美托咪定2 μg/kg+全身喷洒凉水致肛温32~35 ℃),每组20只。除假手术组行假手术外,其余各组大鼠复制脓毒症模型,结扎切开后颈静脉泵入相应药物及维持相应体温。术后6 h采血,采用酶联免疫吸附试验法测定血浆中白细胞介素1(IL-1)、IL-6、肿瘤坏死因子α(TNF-α)浓度;称质量计算肺湿质量/干质量比(W/D);采用苏木精-伊红(HE)染色观察肺组织病理切片,并进行肺损伤评分;采用免疫比浊法测定肺组织中髓过氧化物酶(MPO)活性,采用Western blot法测定肺组织中HMGB1、TLR4及Trem-1蛋白表达。结果:与假手术组比较,模型组大鼠血浆中IL-1、IL-6、TNF-α浓度,W/D,肺损伤评分,肺组织中MPO活性和HMGB1、TLR4、Trem-1蛋白表达水平均明显升高,差异均有统计学意义(P<0.05);肺组织切片显示,肺泡壁明显增厚,出现大量炎性细胞浸润,血管明显扩张、充血。与模型组比较,右美托咪定组、亚低温组和联合组大鼠上述指标均明显降低,差异均有统计学意义(P<0.05);肺组织病理改变程度明显减轻。与右美托咪定组、亚低温组比较,联合组大鼠上述指标降低程度更明显,差异均有统计学意义(P<0.05);肺泡壁增厚和炎性细胞浸润明显减轻,血管未出现扩张、充血。结论:右美托咪定联合亚低温处理可明显改善脓毒症模型大鼠肺损伤,下调肺组织中HMGB1、TLR4、Trem-1蛋白表达,且联合处理改善效果优于单独处理。
ABSTRACT: OBJECTIVE: To investigate the effects of dexmedetomidine combined with mild hypothermia on the levels of High mobility group box 1 protein (HMGB1), Toll like receptor 4 (TLR4) and Triggering receptor expressed on myeloid cells 1 (Trem-1) in lung tissues of sepsis model rats. METHODS: Totally 100 SD rats were randomly divided into sham operation group (normal saline), model group (normal saline), dexmedetomidine group (2 μg/kg), mild hypothermia group (normal saline+anal temperature 32-35 ℃ caused by whole body spraying of cold water) and combination group (dexmedetomidine 2 μg/kg+anal temperature 32-35 ℃ caused by whole body spraying of cold water), with 20 rats in each group. Except that sham operation group received sham operation, sepsis model was induced in other groups. After ligation and incision, the corresponding drugs were pumped into the jugular vein and the corresponding body temperature was maintained. Plasma samples were collected 6 h after operation. Interleukin 1 (IL-1), IL-6, tumor necrosis factor α (TNF-α) were determined by ELISA. The lung wet mass/dry mass ratio (W/D) was calculated by weighing the mass. Lung tissue sections were observed by HE staining, and lung injury scores were scored. The activity of MPO in lung tissue was determined by immunoturbidimetry. The expression of HMGB1,TLR4 and Trem-1 protein was determined by Western blot. RESULTS: Compared with sham operation group, the contents of IL-1, IL-6 and TNF-α, W/D, lung injury score, MPO activity, the protein expression of HMGB1, TLR4 and Trem-1 were increased significantly, with statistical significance (P<0.05); lung tissue section showed that alveolar wall was obviously thickened; a large number of inflammatory cells infiltrated; blood vessels were obviously dilated and congested. Compared with model group, above indexes of rats in dexmedetomidine group, mild hypothermia group and combination group were decreased significantly, with statistical significance (P<0.05); the degree of pathological changes in lung tissue was significantly reduced. Compared with dexmedetomidine group and mild hypothermia group, above indexes of combination group were decreased more significantly, with statistical significance (P<0.05). Alveolar walls were thickened, inflammatory cell infiltration was relieved significantly and no vascular diatation and congestion was found. CONCLUSIONS: Dexmedetomidine combined with mild hypothermia can significantly improve lung injury in sepsis model rats, and down-regulate the protein expression of HMGB1, TLR4 and Trem-1. Therapeutic efficacy of combination therapy is better than single therapy.
期刊: 2019年第30卷第7期
作者: 黎仕焕,李繁,黄奕第
AUTHORS: LI Shihuan,LI Fan,HUANG Yidi
关键字: 右美托咪定;亚低温;脓毒症;大鼠;高迁移率族蛋白B1;Toll样受体4;髓样细胞触发受体1
KEYWORDS: Dexmedetomidine; Mild hypothermia; Sepsis; Rats; High mobility group box 1 protein; Toll like receptor 4; Triggering receptor expressed on myeloid cells 1
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