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HO-1/CO 信号通路对切口痛大鼠炎症因子的调控作用
引用本文:王云涛,单世民 △,刘晓智. HO-1/CO 信号通路对切口痛大鼠炎症因子的调控作用[J]. 天津医药, 2016, 44(9): 1073-1077. DOI: 10.11958/20160268
作者姓名:王云涛  单世民 △  刘晓智
作者单位:1 天津第五中心医院麻醉科(邮编 300450), 2 中心实验室
基金项目:天津市卫生局科技基金资助项目(2014KZ016)
摘    要:目的 观察脊髓血红素氧合酶-1(HO-1)/CO 信号通路对切口痛大鼠炎症因子的调节作用及可能机制。方法 切口痛模型大鼠 36 只在实验即刻(0 h), 术后 1、4、8、12 及 24 h 各处死 6 只, 取患侧脊髓腰膨大处, Western blot 法检测 HO-1 蛋白表达, 酶联免疫吸附试验(ELISA)法检测炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6 和高迁移率族蛋白 1(HMGB1)。 另外, 对照(C)组 36 只大鼠不做切口痛模型;切口痛模型大鼠 144 只按处理方式不同分为切口痛(IP)组, 切口痛+HO-1 诱导剂(IP+hemin)组, 术前给予腹腔注射大鼠 100 mg/kg 血红素(hemin); 切口痛+HO-1 抑制剂(IP+Znpp-IX)组, 术前给予腹腔注射大鼠 45 μmoL/kg 锌原卟啉(Znpp)-IX; 切口痛+ CO 释放剂(IP+CORM-2)组, 于术前经腹腔注射给予 10 mg/kg 一氧化碳释放分子(CORM)-2。 各组于实验即刻(0 h), 术后 1、4、8、12 及 24 h 行机械缩足阈值(PWMT)和热缩足潜伏期(PWTL)的检测, 应用 ELISA 法检测各组 TNF- α、IL-1β、IL-6 和 HMGB1 的表达情况。 结果 与 0 h 比较, 术后 1、4、8、12 及 24 h HO-1 蛋白表达水平和 TNF-α、 IL-1β、IL-6 和 HMGB1 均增高(P< 0.05)。 与 C 组比较, 其余组大鼠各时间点 PWMT 值和 PWTL 值减少, TNF-α、 IL-1β、IL-6 和 HMGB1 表达增加(P< 0.05); 与 IP 组比较, IP+hemin 组和 IP+CORM-2 组大鼠 1、4、8、12 及 24 h 时 PWMT 值和 PWTL 值均增高, 而 TNF-α、IL-1β、IL-6 和 HMGB1 表达减少, IP+Znpp-IX 组 PWMT 值和 PWTL 值降低, 但 TNF-α、IL-1β、IL-6 和 HMGB1 表达增加(P< 0.05)。 结论 切口痛可诱发大鼠 HO-1 表达增加, 而 HO-1/CO 信号通路在调控切口痛大鼠炎症因子的释放方面发挥重要作用。

关 键 词:疼痛   手术后  炎症  疾病模型   动物  肿瘤坏死因子 α  白细胞介素 1β  高迁移率族蛋白 1  血红素氧合酶-1  HO-1/CO 信号通路  
收稿时间:2016-04-07
修稿时间:2016-06-23

The regulatory effect of HO-1 /CO pathway on inflammatory cytokines in a rat model of incisional pain
WANG Yuntao,SHAN Shimin△,LIU Xiaozhi. The regulatory effect of HO-1 /CO pathway on inflammatory cytokines in a rat model of incisional pain[J]. Tianjin Medical Journal, 2016, 44(9): 1073-1077. DOI: 10.11958/20160268
Authors:WANG Yuntao  SHAN Shimin△  LIU Xiaozhi
Affiliation:1 Department of Anesthesiology, 2 Central Laboratory, Tianjin Fifth Central Hospital, Tianjin 300450, China
Abstract:Objective To investigate the effects of HO/CO pathway on inflammation cytokines in a rat model of incisional pain. Methods Thirty-six rats were executed to collect ipsilateral spinal cord tissues for HO- 1 detection by Western blot assay, and cytokines tumor necrosis factor (TNF)- a, interleukin (IL)-1b, IL-6 and high mobility group box (HMGB)1 were detected by ELISA before and at 1, 4, 8, 12 and 24 h after establishing incisional pain model. Additionally, 36 rats without establishment of incisional pain model were used as control group. A total of 144 model rats of incisional pain were divided into incisional pain (IP) group, IP+hemin group (100 mg/kg hemin was injected by i.p. before operation), IP+ Znpp-IX group (45 μmoL/kg Znpp-IX was injected by i.p. before operation) and IP+CORM-2 group (10 mg/kg CORM-2 was injected by i.p. before operation). Values of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were detected, and expressions of TNF-a, IL-1 b, IL-6 and HMGB1 were measured by ELISA before and at 1, 4, 8, 12 and 24 h after operation. Results Compared with pre-operation of incisional pain in rats, expression levels of HO-1 protein and cytokines TNF-a, IL-1 b, IL-6 and HMGB1 were increased at 1, 4, 8, 12 and 24 h after operation (P< 0.05). Compared with control group, values of PWMT and PWTL were obviously decreased, and expression levels of IL-1β, TNF-α, IL-6 and HMGB1 were increased at 1, 4, 8, 12 and 24 h after operation in IP groups (P< 0.05). Compared with IP groups, values of PWMT and PWTL were significantly increased and cytokines TNF- a, IL-1 b, IL-6 and HMGB1 were decreased at 1, 4, 8, 12 and 24 h after operation in IP+hemin group and IP+CORM-2 group (P< 0.05). Values of PWMT and PWTL were decreased and cytokines TNF-α, IL-1β, IL-6 and HMGB1 were increased in IP+Znpp-IX group (P< 0.05). Conclusion Incisional pain can increase the expression of HO-1, and HO-1/CO pathway exists the regulatory effect on inflammatory cytokines in the rat model of incisional pain.
Keywords:pain   postoperation  inflammation  disease models   animal  tumor necrosis factor-alpha  interleukin-1beta  high mobility group protein 1  heme oxygenase 1  HO-1/CO signal path  
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