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

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

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5 mg/kg组(n=15)、利多卡因10 mg/kg组(n=15)、利多卡因20 mg/kg组(n=15)。CLP术后0、1、2 h S组和NS组分别腹腔内注射生理盐水0.5 mL,利多卡因各组分别注射利多卡因5、10和20 mg/kg。24 h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、20 mg/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。

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（P0.05）.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,P0.05].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.