本文選題：利多卡因 + 高遷移率族蛋白B1　； 參考：《山東大學(xué)》2014年碩士論文

【摘要】：目的： 手術(shù)創(chuàng)傷可引起人體神經(jīng)、內(nèi)分泌、代謝、炎性反應(yīng)等一系列生理功能改變。手術(shù)刺激引起過度炎癥反應(yīng)和免疫抑制是導(dǎo)致術(shù)后病死率升高,繼發(fā)全身炎癥反應(yīng)綜合征(systemic inflammatory response syndrome, SIRS)、呼吸窘迫綜合征(acute respiratory distress syndrome, ARDS)、多器官功能衰竭(multiple organ dysfunction syndrome, MODS)的重要因素。高遷移率族蛋白B1(HMGB1)是廣泛存在于體內(nèi)細(xì)胞核中的一種DNA結(jié)合蛋白,在組織損傷或免疫細(xì)胞受到病原體刺激后主要由單核細(xì)胞或巨噬細(xì)胞通過非經(jīng)典途徑分泌到細(xì)胞外,發(fā)揮促炎癥因子和化學(xué)趨化因子的作用,HMGB1可通過自身毒性作用、刺激其他促炎因子釋放等多種途徑誘導(dǎo)不同炎癥反應(yīng)的發(fā)生,其過表達(dá)與大手術(shù)后全身炎癥反應(yīng)和膿毒癥的發(fā)生密切相關(guān)。而利多卡因在炎癥過程中發(fā)揮負(fù)性調(diào)節(jié)作用,并可減輕術(shù)后疼痛、加快胃腸功能恢復(fù),從而促進(jìn)術(shù)后早期康復(fù),利多卡因促進(jìn)患者術(shù)后早期康復(fù)的機(jī)制尚不明確。本研究通過觀察利多卡因靜脈輸注對宮頸癌根治術(shù)患者術(shù)中血流動力學(xué)改變、術(shù)后腹部疼痛評分、腹部舒適度評分和惡心嘔吐評分及圍術(shù)期單核細(xì)胞HMGB1釋放的影響,探究利多卡因圍術(shù)期應(yīng)用在患者早期康復(fù)中發(fā)揮的作用及其機(jī)制。方法： 該試驗(yàn)方案經(jīng)山東大學(xué)齊魯醫(yī)院倫理委員會審查批準(zhǔn),由患者同意并簽署知情同意書,選擇2013年6月至2014年1月已確診宮頸癌且于山東大學(xué)齊魯醫(yī)院第一手術(shù)室擇期行宮頸癌根治術(shù)的患者30例,按照隨機(jī)數(shù)表法將其分為對照組(C)和利多卡因組(L),每組各15例(n=15)。 所有患者均實(shí)行全身麻醉,術(shù)前常規(guī)禁食水8-12h,于麻醉前30min肌肉注射阿托品0.5mg,苯巴比妥鈉100mg。病人進(jìn)入手術(shù)間后常規(guī)監(jiān)測心電圖(EKG)、血壓(BP)、心率(HR)、脈搏血氧飽和度(SpO2)、呼氣末二氧化碳分壓(PetC02),麻醉誘導(dǎo)前15min利多卡因組靜推利多卡因1.5mg/kg (5min),隨后微量泵靜脈輸注2%利多卡因1.5mg· kg-1· h-1至病人離開手術(shù)間。對照組給予相等容量的生理鹽水。予以咪達(dá)唑侖0. lmg/kg,丙泊酚1-1.5mg/kg,芬太尼2μg/kg,病人睫毛反射消失后靜注羅庫溴銨0.6mg/kg,純氧通氣3分鐘后氣管插管,進(jìn)行機(jī)械通氣。插管后予以七氟醚吸入維持麻醉,根據(jù)需要追加阿曲庫銨。術(shù)中維持BP、HR穩(wěn)定；調(diào)節(jié)呼吸參數(shù),維持PetC0235-45mmHg。于手術(shù)前24h、手術(shù)結(jié)束即刻、手術(shù)結(jié)束后48h,分別采取靜脈血10m1。采用密度梯度法留取血漿并獲取單核細(xì)胞,將單核細(xì)胞分為直接培養(yǎng)組和LPS刺激組,培養(yǎng)24h, ELISA法測定血漿及兩組細(xì)胞培養(yǎng)液上清中HMGB1蛋白。Trizol法提取細(xì)胞總RNA,實(shí)時定量RT-PCR法測定單核細(xì)胞HMGB1mRNA。同時隨訪兩組病人術(shù)后首次排氣、排便時間,記錄術(shù)后6h、術(shù)后24h、術(shù)后48h安靜及咳嗽時腹部疼痛VAS評分,腹部舒適度VAS評分以及病人惡心嘔吐VAS評分。結(jié)果： 1.血流動力學(xué)變化：兩組病人麻醉前心率、收縮壓、舒張壓、平均動脈壓基礎(chǔ)值比較無統(tǒng)計學(xué)差異(P0.05)。手術(shù)切皮時、氣管插管即刻、關(guān)閉腹膜時及氣管拔管即亥SBP、DBP、MAP和HR,C組高于L組(P0.05)。 2.血漿及細(xì)胞培養(yǎng)上清中HMGB1蛋白水平：血漿中HMGB1蛋白水平,術(shù)后48h時L組(53.458±8.983μ g/L)低于C組(59.387±5.025μ g/L),差異有統(tǒng)計學(xué)意義(P0.05)；單核細(xì)胞直接培養(yǎng)組細(xì)胞培養(yǎng)上清中術(shù)后48h時L組(64.049±11.24μ g/L)較之C組(71.801±9.191μ g/L)低(P0.05)；單核細(xì)胞LPS刺激組細(xì)胞培養(yǎng)上清中HMGB1蛋白水平,術(shù)后48h時L組(80.249±5.938μ g/L)顯著低于C組(88.168±9.05μ g/L),差異有統(tǒng)計學(xué)意義(P0.01)。 3.單核細(xì)胞HMGB1mRNA水平：直接培養(yǎng)組術(shù)后48h時L組HMGB1mRNA表達(dá)水平低至C組的53%,差異有統(tǒng)計學(xué)意義(P0.05)；LPS刺激組術(shù)后48h時L組HMGB1mRNA表達(dá)水平低至C組的59%,差異有統(tǒng)計學(xué)意義(P0.05)。 4.病人首次排氣、排便時間：L組病人首次排氣、排便時間(20.4±3.4h、66.4±4.2h)較C組(29.1±3.9h、77.8±5.1h)顯著早(P0.05)。 5.術(shù)后腹部疼痛VAS,腹部舒適度VAS及惡心嘔吐VAS：術(shù)后L組病人腹部疼痛VAS及惡心嘔吐VAS評分較之C組低(P0.05),而腹部舒適度VAS,顯著高于C組病人(P0.05)。 結(jié)論： 利多卡因圍術(shù)期靜脈輸注可促進(jìn)宮頸癌患者胃腸功能早期恢復(fù),減少術(shù)后疼痛和惡心嘔吐,提高病人舒適度。原因可能與其抑制手術(shù)病人高遷移率族蛋白B1的釋放有關(guān)。因此,圍術(shù)期靜脈輸注利多卡因有益于手術(shù)病人的恢復(fù),有一定的臨床應(yīng)用價值。
[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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.33

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