利多卡因静脉输注对宫颈癌根治术患者术后早期康复及HMGB1释放的影响

发布时间：2018-06-26 00:36

本文选题：利多卡因 + 高迁移率族蛋白B1　；参考：《山东大学》2014年硕士论文

【摘要】：目的：手术创伤可引起人体神经、内分泌、代谢、炎性反应等一系列生理功能改变。手术刺激引起过度炎症反应和免疫抑制是导致术后病死率升高,继发全身炎症反应综合征(systemic inflammatory response syndrome, SIRS)、呼吸窘迫综合征(acute respiratory distress syndrome, ARDS)、多器官功能衰竭(multiple organ dysfunction syndrome, MODS)的重要因素。高迁移率族蛋白B1(HMGB1)是广泛存在于体内细胞核中的一种DNA结合蛋白,在组织损伤或免疫细胞受到病原体刺激后主要由单核细胞或巨噬细胞通过非经典途径分泌到细胞外,发挥促炎症因子和化学趋化因子的作用,HMGB1可通过自身毒性作用、刺激其他促炎因子释放等多种途径诱导不同炎症反应的发生,其过表达与大手术后全身炎症反应和脓毒症的发生密切相关。而利多卡因在炎症过程中发挥负性调节作用,并可减轻术后疼痛、加快胃肠功能恢复,从而促进术后早期康复,利多卡因促进患者术后早期康复的机制尚不明确。本研究通过观察利多卡因静脉输注对宫颈癌根治术患者术中血流动力学改变、术后腹部疼痛评分、腹部舒适度评分和恶心呕吐评分及围术期单核细胞HMGB1释放的影响,探究利多卡因围术期应用在患者早期康复中发挥的作用及其机制。方法：该试验方案经山东大学齐鲁医院伦理委员会审查批准,由患者同意并签署知情同意书,选择2013年6月至2014年1月已确诊宫颈癌且于山东大学齐鲁医院第一手术室择期行宫颈癌根治术的患者30例,按照随机数表法将其分为对照组(C)和利多卡因组(L),每组各15例(n=15)。所有患者均实行全身麻醉,术前常规禁食水8-12h,于麻醉前30min肌肉注射阿托品0.5mg,苯巴比妥钠100mg。病人进入手术间后常规监测心电图(EKG)、血压(BP)、心率(HR)、脉搏血氧饱和度(SpO2)、呼气末二氧化碳分压(PetC02),麻醉诱导前15min利多卡因组静推利多卡因1.5mg/kg (5min),随后微量泵静脉输注2%利多卡因1.5mg· kg-1· h-1至病人离开手术间。对照组给予相等容量的生理盐水。予以咪达唑仑0. lmg/kg,丙泊酚1-1.5mg/kg,芬太尼2μg/kg,病人睫毛反射消失后静注罗库溴铵0.6mg/kg,纯氧通气3分钟后气管插管,进行机械通气。插管后予以七氟醚吸入维持麻醉,根据需要追加阿曲库铵。术中维持BP、HR稳定；调节呼吸参数,维持PetC0235-45mmHg。于手术前24h、手术结束即刻、手术结束后48h,分别采取静脉血10m1。采用密度梯度法留取血浆并获取单核细胞,将单核细胞分为直接培养组和LPS刺激组,培养24h, ELISA法测定血浆及两组细胞培养液上清中HMGB1蛋白。Trizol法提取细胞总RNA,实时定量RT-PCR法测定单核细胞HMGB1mRNA。同时随访两组病人术后首次排气、排便时间,记录术后6h、术后24h、术后48h安静及咳嗽时腹部疼痛VAS评分,腹部舒适度VAS评分以及病人恶心呕吐VAS评分。结果： 1.血流动力学变化：两组病人麻醉前心率、收缩压、舒张压、平均动脉压基础值比较无统计学差异(P0.05)。手术切皮时、气管插管即刻、关闭腹膜时及气管拔管即亥SBP、DBP、MAP和HR,C组高于L组(P0.05)。 2.血浆及细胞培养上清中HMGB1蛋白水平：血浆中HMGB1蛋白水平,术后48h时L组(53.458±8.983μ g/L)低于C组(59.387±5.025μ g/L),差异有统计学意义(P0.05)；单核细胞直接培养组细胞培养上清中术后48h时L组(64.049±11.24μ g/L)较之C组(71.801±9.191μ g/L)低(P0.05)；单核细胞LPS刺激组细胞培养上清中HMGB1蛋白水平,术后48h时L组(80.249±5.938μ g/L)显著低于C组(88.168±9.05μ g/L),差异有统计学意义(P0.01)。 3.单核细胞HMGB1mRNA水平：直接培养组术后48h时L组HMGB1mRNA表达水平低至C组的53%,差异有统计学意义(P0.05)；LPS刺激组术后48h时L组HMGB1mRNA表达水平低至C组的59%,差异有统计学意义(P0.05)。 4.病人首次排气、排便时间：L组病人首次排气、排便时间(20.4±3.4h、66.4±4.2h)较C组(29.1±3.9h、77.8±5.1h)显著早(P0.05)。 5.术后腹部疼痛VAS,腹部舒适度VAS及恶心呕吐VAS：术后L组病人腹部疼痛VAS及恶心呕吐VAS评分较之C组低(P0.05),而腹部舒适度VAS,显著高于C组病人(P0.05)。结论：利多卡因围术期静脉输注可促进宫颈癌患者胃肠功能早期恢复,减少术后疼痛和恶心呕吐,提高病人舒适度。原因可能与其抑制手术病人高迁移率族蛋白B1的释放有关。因此,围术期静脉输注利多卡因有益于手术病人的恢复,有一定的临床应用价值。
[Abstract]:Objective:
Surgical trauma can cause a series of physiological functions, such as nerve, endocrinology, metabolism, and inflammatory response. The excessively inflammatory response and immunosuppression caused by surgical stimulation are the causes of postoperative mortality, secondary systemic inflammatory response syndrome (systemic inflammatory response syndrome, SIRS), and respiratory distress syndrome (acute respiratory DI). Stress syndrome, ARDS), an important factor in multiple organ failure (multiple organ dysfunction syndrome, MODS). The high mobility group protein B1 (HMGB1) is a kind of DNA binding protein that widely exists in the nucleus of the body. After tissue damage or immune cells are stimulated by the pathogen, it is mainly by monocyte or macrophage through non classic. The pathway is secreted outside the cell and plays the role of pro-inflammatory and chemical chemokines. HMGB1 can induce the occurrence of different inflammatory reactions in many ways, such as its toxicity and other pro-inflammatory factors, which are closely related to the systemic inflammatory response and the occurrence of sepsis. The mechanism of negative regulation can reduce postoperative pain, accelerate the recovery of gastrointestinal function, and promote early postoperative rehabilitation. The mechanism of lidocaine to promote the early recovery of the patients is not clear. Effects of abdominal comfort score, nausea and vomiting score and HMGB1 release during perioperative period, and explore the role and mechanism of lidocaine perioperative application in the early rehabilitation of patients.
The experimental scheme was approved by the ethics committee of Qilu Hospital of Shandong University. The patients agreed and signed the informed consent. 30 cases of cervical cancer diagnosed from June 2013 to January 2014 were selected and 30 cases of radical operation of cervical cancer at the first operation room of the operation room in the operation room were divided into the control group (C) and the profit. The docaine group (L), 15 cases (n=15) in each group.
All patients were subjected to general anesthesia, conventional fasting water 8-12h before operation, 30min intramuscular injection of atropine 0.5mg before anesthesia, and routine monitoring of electrocardiogram (EKG), blood pressure (BP), heart rate (HR), pulse oxygen saturation (SpO2), end expiratory carbon dioxide pressure (PetC02), and 15min lidocaine group before induction of anesthesia in patients with phenobarbital sodium 100mg.. Static push lidocaine 1.5mg/kg (5min), then intravenous infusion of 2% lidocaine 1.5mg / kg-1 / H-1 to the patients to leave the operation. The control group was given equal volume of physiological saline. Midazolam was given 0. lmg/kg, propofol 1-1.5mg/kg, fentanyl 2 u g/kg, patients with cilia reflex disappeared after the intravenous infusion of rocuronium 0.6mg/kg, pure oxygen ventilation 3 minutes After endotracheal intubation, mechanical ventilation was performed. After intubation, sevoflurane was inhaled to maintain anaesthesia, and atracurium was added to maintain BP and HR during the operation. The respiratory parameters were maintained, the PetC0235-45mmHg. was maintained before the operation 24h, the operation was immediately after the end of the operation, and 48h was obtained after the operation, and the density gradient method was used to obtain the plasma and obtain the plasma and obtain the blood plasma. Mononuclear cells were divided into direct culture group and LPS stimulation group. 24h was cultured, ELISA method was used to determine plasma and HMGB1 protein.Trizol method in two groups of cell culture liquid to extract the total RNA. The real-time quantitative RT-PCR method was used to determine the mononuclear cell HMGB1mRNA. at the same time and the two groups were followed up for the first time, the time of defecation, and the postoperative 6h and 24h, after the operation. Postoperative 48h was mild and cough abdominal pain VAS score, abdominal comfort VAS score and patient nausea and vomiting VAS score.
1. hemodynamic changes: there was no significant difference in heart rate, systolic pressure, diastolic pressure and mean arterial pressure in the two groups (P0.05). During surgical incision, the tracheal intubation was immediately, the peritoneum was closed and the tracheal extubation was SBP, DBP, MAP and HR, and the C group was higher than the L group (P0.05).
2. the level of HMGB1 protein in plasma and cell culture supernatant: the level of HMGB1 protein in plasma and L group (59.387 + 5.025 g/L) at 48h after operation (59.387 + 5.025 g/L), the difference was statistically significant (P0.05), and the L group (64.049 + 11.24 mu g/L) in the cell culture supernatant of monocyte direct culture group (64.049 + 11.24 mu g/L) was compared with the C group (71.801 + 9.191 mu). Low (P0.05); the level of HMGB1 protein in the cell culture supernatant of monocyte LPS stimulation group. The L group (80.249 + 5.938 mu g/L) in L group after 48h was significantly lower than that of the C group (88.168 + 9.05 mu g/L), the difference was statistically significant (P0.01).
3. HMGB1mRNA level of monocyte: the expression level of HMGB1mRNA in group L was lower than 53% in group C after operation in direct culture group, and the difference was statistically significant (P0.05). The expression level of L group HMGB1mRNA in LPS stimulation group was lower than that of 59% in C group when 48h was 48h, and the difference was statistically significant (P0.05).
4. patients first exhaust, defecation time: group L patients exhaust for the first time, defecation time (20.4 + 3.4h, 66.4 + 4.2h) is significantly earlier than group C (29.1 + 3.9h, 77.8 + 5.1h) (P0.05).
5. postoperative abdominal pain VAS, abdominal comfort VAS and nausea and vomiting VAS: postoperative abdominal pain VAS and nausea and vomiting VAS score in group L patients were lower than that of the C group (P0.05), and the abdominal comfort degree was VAS, significantly higher than the C group (P0.05).
Conclusion:
Intravenous infusion of lidocaine can promote the early recovery of gastrointestinal function in patients with cervical cancer, reduce postoperative pain, nausea and vomiting, and improve the patient's comfort. The reason may be related to the inhibition of the release of high mobility group protein B1 of the patients. Therefore, intravenous infusion of lidocaine is beneficial to the recovery of the patients in the operation. The application value of bed.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33

【参考文献】