国际麻醉学与复苏杂志   2024, Issue (11): 0-0
    
持续静脉泵注利多卡因对脓毒症早期大鼠肾损伤的影响
张贵超, 张宇轩, 李青青, 徐桂萍1()
1.石河子大学研究生院
Effect of continuous intravenous lidocaine on kidney injury in rats with early sepsis
 全文:
摘要:

目的 探讨持续静脉泵注利多卡因对脓毒症早期大鼠肾损伤的影响。 方法 选择160只SPF级雄性SD大鼠,采用随机数字表法将120只雄性SD大鼠分为4组(每组30只):假手术组(S组)、盲肠结扎穿孔组(CLP组)、利多卡因组(L组)和生理盐水组(N组)。S组大鼠打开腹腔后立即缝合,其余组采用盲肠结扎穿孔(CLP)法建立脓毒症模型。L组建模完成后即刻给予利多卡因负荷量10mg/kg,再以10mg·kg-1·h-1剂量持续尾静脉泵注利多卡因3h;N组以等体积生理盐水替代。于仅开腹(T0)、CLP术后2h末(T1)、4h末(T2)、8h末(T3)、20h末(T4)、24h末(T5)6个时点各随机选取5只大鼠麻醉后迅速采集下腔静脉血液,采用酶联免疫吸附(ELISA)法测定血清IL-6、TNF-α、SCr、BUN、胱抑素C(Cys-C)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)浓度,苏木精–伊红(HE)染色观察肾脏组织病理变化,收集并测定各组8h、24h尿量。另取40只大鼠分组处理同上用于观察4组大鼠72h生存情况。 结果 S组存活率100%,CLP组存活率10%,L组存活率60%,N组存活率40%。与S组比较,余3组血清IL-6、TNF-α均升高;与CLP组比较,L组降低;N组与CLP组无统计学差异。与S组比较,CLP组尿量减少,L组和N组尿量增加。与S组比较,CLP组、L组和N组T1-5时点血清SCr、BUN、Cys-C和NGAL浓度均升高(P0.05);与CLP组比较,L组T1-5时点血清SCr、BUN、Cys-C和NGAL浓度均降低(P0.05),N组T1-2、T5时点血清SCr浓度降低(P0.05),N组T1、T4-5时点血清BUN浓度降低(P0.05),N组T1、T3-5时点血清Cys-C浓度降低(P0.05),N组T1、T4-5时点血清NGAL浓度降低(P0.05);与N组比较,L组T¬2-3时点血清SCr浓度、T1-3时点血清BUN浓度、T1-5时点血清Cys-C、NGAL浓度均降低 (P0.05)。 结论 通过持续静脉泵注利多卡因能增加液体容量,降低IL-6、TNF-α水平,减轻脓毒症早期肾脏损伤,抑制脓毒症早期大鼠血清SCr、BUN、Cys-C、NGAL浓度升高。

关键词: 脓毒症;炎性因子;急性肾损伤;静脉泵注;利多卡因
Abstract:

Objective To investigate the effect of continuous intravenous lidocaine on kidney injury in rats with early sepsis. Methods A total of 160 SPF male SD rats were randomly divided into 4 groups (30 rats in each group): sham operation group (group S), cecal ligation and perforation group (group CLP), lidocaine group (group L) and normal saline group (group N). The rats in group S were sutured immediately after opening the abdominal cavity, and the sepsis model was established by cecal ligation and perforation (CLP) method in the remaining groups. Immediately after the completion of modeling, group L was given lidocaine loading of 10 mg/kg, followed by continuous tail vein pumping lidocaine at a dose of 10 mg·kg-1·h-1 for 3 hours, and group N was replaced with the same volume of normal saline. Five rats were randomly selected at 6 time points after anesthesia (T0), 2 h (T1), 4 h (T2), 8 h (T3), 20 h (T4) and 24 h (T5) after laparotomy only, and serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α), SCr, BUN, cystatin C (Cys-C) and neutrophil gelatinase-associated lipid carrier protein were determined by enzyme-linked immunosorbent assay (ELISA). (NGAL) concentration, hematoxylin–eosin (HE) staining was used to observe the pathological changes of kidney tissue, and the urine output of each group was collected and measured at 8h and 24h. Another 40 rats were grouped and processed as above, and the survival of 4 groups of rats was observed for 72 hours. Results The survival rate was 100% in group S, 10% in group CLP, 60% in group L, and 40% in group N. Compared with the group S, the serum IL-6 and TNF-α in the groups CLP, L and N increased, while those in the group L decreased compared with the CLP, and there was no statistically significant difference between the group N and the group CLP. Compared with the group S, the urine output of the group CLP decreased, and the urine output of the groups L and N increased. Compared with group S, the serum concentrations of SCr, BUN, Cys-C and NGAL in group CLP, groups L and N were increased at T1-5 (P0.05), compared with the group CLP, the serum concentrations of SCr, BUN, Cys-C and NGAL at T1-5 in group L decreased (P0.05), the serum SCr concentrations at T1-2 and T5 in group N decreased (P0.05), the serum BUN concentrations at T1 and T4-5 in group N decreased (P0.05), and the serum concentrations of Cys-C at time T1 and T3-5 decreased in group N (P0.05), the serum NGAL concentrations at T1 and T4-5 in group N decreased (P0.05), and compared with group N, serum SCr concentrations at T2-3, serum BUN concentrations at T1-3, serum Cys-C and NGAL concentrations at T1-5 were decreased in group L (P0.05). Conclusion Continuous intravenous injection of lidocaine can increase fluid volume, reduce the levels of IL-6 and TNF-α, alleviate kidney injury in the early stage of sepsis, and inhibit the increase of serum SCr, BUN, Cys-C and NGAL concentrations in rats with early sepsis.

Key words: Sepsis; Inflammatory factors; Acute kidney injury; intravenous pumping; lidocaine