利多卡因对大鼠内毒素性肺损伤时Rho/ROCK信号通路的影响  

Effect of lidocaine on Rho/ROCK signaling pathway during endotoxin-induced acute lung injury in rats

作　　者：张琳 张伟 张加强 孟凡民 Zhang Lin;Zhang Wei;Zhang Jiaqiang;Meng Fanmin(Department of Anesthesiology, Henan Province People′s Hospital(People′s Hospital of Zhengzhou University), Zhengzhou 450003, China)

机构地区：[1]河南省人民医院(郑州大学人民医院)麻醉科,450003

出　　处：《中华麻醉学杂志》2019年第1期109-112,共4页Chinese Journal of Anesthesiology

基　　金：河南省科技攻关项目(182102310167);河南省医学科技攻关项目(201602227).

摘　　要：目的评价利多卡因对大鼠内毒素性肺损伤时Ras同源基因(Rho)/Rho激酶(ROCK)信号通路的影响。方法SPF级雄性大鼠Wistar大鼠40只,5~8周龄,体重200~250 g。采用随机数字表法分为5组(n=8):对照组(C组)、LPS组和不同剂量利多卡因组(L1-3组)。采用腹腔注射LPS 5 mg/kg(0.1 ml)的方法制备内毒素性肺损伤模型,C组腹腔注射等量生理盐水。腹腔注射LPS前1 h时,L1-3组分别腹腔注射利多卡因2 、4和8 mg/kg。注射LPS或生理盐水后6 h时处死大鼠,制备支气管肺泡灌洗液(BALF),采用ELISA法测定IL-1β、IL-6及TNF-α的浓度;取肺组织,行肺损伤评分,计算湿重/干重(W/D)比值,测定髓过氧化物酶(MPO)活性,采用Western blot法测定肺组织Rho、ROCK1、ROCK2、肌球蛋白磷酸酯酶目标亚基1(MYPT1)、磷酸化MYPT1(p-MYPT1)和ZO-1的表达。计算MYPT1磷酸化水平。结果与C组比较,其余4组肺组织MPO活性、肺损伤评分、W/D比值、BALF IL-1β、IL-6及TNF-α浓度升高,肺组织Rho、ROCK1和ROCK2表达上调,MYPT1磷酸化水平升高,ZO-1表达下调(P<0.05);与LPS组比较,L1-3组肺组织MPO活性、肺损伤评分、W/D比值、BALF IL-1β、IL-6及TNF-α浓度降低,肺组织Rho、ROCK1和ROCK2表达下调,MYPT1磷酸化水平降低,ZO-1表达上调(P<0.05)。结论利多卡因可抑制大鼠内毒素性肺损伤时Rho/ROCK信号通路活性,该作用可能与利多卡因的抗炎机制有关。Objective To evaluate the effect of lidocaine on Ras homologue(Rho)/Rho kinase(ROCK)signaling pathway during endotoxin-induced lung injury(LI) in rats. Methods Forty SPF male Wistar rats, aged 5-8 weeks, weighing 200-250 g, were divided into 5 groups(n=8 each)using a random number table method: control group(group C), lipopolysaccharide(LPS)group(group LPS)and lidocaine at 3 different doses groups(L1-3 groups). LI was induced by intraperitoneal LPS 5 mg/kg(0.1 ml). The equal volume of normal saline was given intraperitoneally in group C. Lidocaine 2, 4 and 8 mg/kg was intraperitoneally injected at 1 h before LPS administration in L1-3 groups, respectively.The animals were sacrificed at 6 h after LPS or normal saline administration.Broncho-alveolar lavage fluid(BALF)was collected for determination of concentrations of interleukin-1 beta(IL-1β), IL-6 and tumor necrosis factor-alpha(TNF-α)(by enzyme-linked immunosorbent assay). The lung tissues were obtained for examination of the pathological changes which were scored and for measurement of the wet/dry weight ratio(W/D ratio)and activities of myeloperoxidase(MPO)and for determination of the expression of Rho, ROCK1, ROCK2, myosin phosphatase target protein 1(MYPT1), phosphorylated MYPT1(p-MYPT1)and ZO-1(by Western blot). The phosphorylation of MYPT1 was calculated. Results Compared with group C, the activity of MPO, lung injury score, W/D ratio and concentrations of IL-1β, IL-6 and TNF-α in BALF were significantly increased, the expression of Rho, ROCK1 and ROCK2 was up-regulated, the phosphorylation of MYPT-1 was increased, and the expression of ZO-1 was down-regulated in the other four groups(P<0.05). Compared with group LPS, the activity of MPO, lung injury score, W/D ratio and concentrations of IL-1β, IL-6 and TNF-α in BALF were significantly decreased, the expression of Rho, ROCK1 and ROCK2 was down-regulated, the phosphorylation of MYPT-1 was decreased, and the expression of ZO-1 was up-regulated in L1-L3 groups(P<0.05). Conclusion Lidocaine can inhibit

关 键 词：利多卡因 RHO因子 RHO相关激酶类 内毒素血症 呼吸窘迫综合征 成人 

分 类 号：R459.7[医药卫生—急诊医学]