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山东大学学报(医学版) ›› 2011, Vol. 49 ›› Issue (11): 21-.

• 论文 • 上一篇    下一篇

利多卡因对脓毒症大鼠肾组织高迁移率族蛋白表达的影响

王焕亮1,2,岳寿伟2,徐迎雪1,荣菲1,类维富1,张文华3   

  1. 山东大学齐鲁医院 1.麻醉科, 2.康复科, 3.神经外科, 济南 250012
  • 出版日期:2011-11-10 发布日期:2011-11-10
  • 通讯作者: 岳寿伟(1962- ),男,教授,博士生导师,主要从脊髓疾病的康复研究。 E-mail: yueshouw@sdu.edu.cn
  • 作者简介:王焕亮(1968- ),男,博士研究生,主要从事手术期器官保护研究。
  • 基金资助:

    山东省自然科学基金资助课题(Y2007C115,2009ZRB14031,JQ200808)

Effect of lidocaine on expression of high mobility group protein box 1 in kidneys of septic rats

WANG Huan-liang1,2, YUE Shou-wei2, XU Ying-xue1, Rong Fei1, LEI Wei-fu1, ZHANG Wen-hua3   

  1. 1. Department of Anesthesiology;  2. Department of Rehabilitation Medicine;
    3. Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan 250012, China
  • Online:2011-11-10 Published:2011-11-10

摘要:

目的   观察利多卡因对盲肠结扎穿孔(CLP)脓毒症大鼠肾组织高迁移率族蛋白B1(HMGB1)表达的影响,探讨利多卡因脓毒症急性肾损伤的保护机制。方法   雄性 Wistar大鼠随机分5组:假手术组(S组,n=15)、生理盐水组(NS组,n=20)、利多卡因5mg/kg组(n=15)、利多卡因10mg/kg组(n=15)、利多卡因20mg/kg组(n=15)。CLP术后0、1、2h S组和NS组分别腹腔内注射生理盐水0.5mL,利多卡因各组分别注射利多卡因5、10和20mg/kg。24h后留取血液和器官标本。实时PCR测定肾组织HMGB1 mRNA表达,生化分析测定血肌酐(Cr)浓度,光镜检查组织病理变化,免疫组化测定器官核转录因子(NFκB)活化。结果   ① 与S组比较,其他4组肾脏HMGB1 mRNA表达增加(P<0.05)。利多卡因各组HMGB1 mRNA水平较NS组降低(P<0.05),呈明显剂量依赖性;② 利多卡因5、10、20mg/kg组大鼠血Cr水平[(44.80±3.70)μmol/L, (34.80±4.44)μmol/L, (27.40±2.30)μmol/L]较NS组[(51.00±5.00)μmol/L]降低(P<0.05);③ 利多卡因处理可明显减轻组织损伤和炎症细胞浸润;④ 利多卡因可抑制CLP诱导的肾组织NFκB活化。结论   利多卡因脓毒症急性肾损伤保护作用可能与其抑制组织HMGB1的过表达有关。

关键词: 利多卡因;脓毒症;高迁移率族蛋白B1;急性肾损伤

Abstract:

Objective   To detect the effect of lidocaine on expression of high mobility group protein box 1(HMGB1) in kidneys of septic rats and investigate its protective mechanism against acute kidney injury. Methods   Wistar rats, subjected to cecal ligation and puncture (CLP), were treated with normal saline or lidocaine of 5, 10 and 20mg/kg at 0 and 1, 2 hour after CLP.  Twenty-four hours after CLP, the level of HMGB1 mRNA and activation of NF-κB p65 in kidneys were assessed, and alteration of histology and concentration of plasma creatinine were determined.  Results   ① Compared with the sham-operated group, the level of HMGB1mRNA in kidneys was significantly increased in rats subjected to CLP, which was suppressed by lidocaine in a dose-dependent manner(P<0.05).  ② Concentrations of plasma creatinine in groups treated with lidocaine of 5, 10 and 20mg/kg [(44.80±3.70), (34.80±4.44) and (27.40±2.30)μmol/L] were significantly decreased compared with the saline-treated group [(51.00±5.0)μmol/L, P<0.05]. ③ Infiltration of inflammatory cells and histological damages induced by CLP were mitigated by lidocaine. ④ Activation of NF-κB p65 in kidneys was also inhibited by lidocaine.  Conclusions   The protective effect of lidocaine on CLP-induced acute kidney injury may be result from its inhibition of expression of HMGB1 in tissues.

Key words: Lidocaine; Sepsis; High mobility protein box 1; Acute kidney injury

中图分类号: 

  • R631
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