本文關(guān)鍵詞：圍術(shù)期利多卡因?qū)m頸癌根治術(shù)患者淋巴細胞功能及HMGB1釋放的影響　出處：《山東大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 宮頸癌 利多卡因 淋巴細胞 高遷移率族蛋白B1

【摘要】：研究背景及目的： 外科手術(shù)及創(chuàng)傷可使機體內(nèi)分泌系統(tǒng)的下丘腦-垂體-腎上腺軸(HPA)功能增強,增強交感神經(jīng)系統(tǒng)的應(yīng)激反應(yīng)及急性期的應(yīng)答反應(yīng),引發(fā)機體應(yīng)激性炎癥反應(yīng)甚至是全身性炎癥反應(yīng)綜合癥,這一過程伴隨著機體免疫系統(tǒng)的激活,促炎介質(zhì)呈高水平加工及釋放,最終導(dǎo)致機體免疫功能迅速受抑,而手術(shù)應(yīng)激導(dǎo)致的免疫抑制效應(yīng),是造成術(shù)后并發(fā)感染及加速殘存腫瘤轉(zhuǎn)移的重要原因。利多卡因作為一種常用的酰胺類局部麻醉藥,不僅具有鎮(zhèn)痛、抗痛覺過敏、抗心律失常的作用,研究顯示其還具有抗炎作用,且圍術(shù)期靜脈輸注利多卡因能夠減輕術(shù)后疼痛,減少阿片類鎮(zhèn)痛藥使用量,減輕機體炎癥反應(yīng),加快胃腸功能恢復(fù)及縮短患者住院時間。高遷移率族蛋白B1(HMGB1)在多種惡性腫瘤中表達異常增高,作為一種晚期炎癥性蛋白,已有研究顯示其可介導(dǎo)機體對感染及損傷的炎癥反應(yīng),從而促進炎癥反應(yīng)的發(fā)生及發(fā)展。本研究通過觀察術(shù)中持續(xù)靜脈輸注小劑量利多卡因?qū)α馨图毎鲋场⒌蛲�、Th1/Th2漂移及HMGB1釋放的影響,探討利多卡因?qū)κ中g(shù)創(chuàng)傷致機體免疫功能下降的保護作用及機制,為利多卡因應(yīng)用于臨床抗炎治療提供理論依據(jù)。 研究方法： 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)室擇期行全身麻醉下宮頸癌根治術(shù)(廣泛子宮切除術(shù)加盆腔淋巴結(jié)清掃術(shù))患者30例,所有患者都簽署醫(yī)學(xué)試驗知情同意書,采用隨機數(shù)字表法,將病人隨機分為對照組(C)和利多卡因組(L),每組各15例(n=15),兩組病人臨床基線無統(tǒng)計學(xué)差異。氣管插管靜吸復(fù)合麻醉。病人進入手術(shù)間后開放利多卡因?qū)Ｓ渺o脈通道,麻醉誘導(dǎo)前15min靜推利多卡因1.5mg/kg(推注時間持續(xù)約10min),麻醉誘導(dǎo)后微量泵靜脈輸注利多卡因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。手術(shù)前24h、手術(shù)后Oh、手術(shù)后48h分別抽取病人靜脈血10ml。離心,收集血漿,分離外周血淋巴細胞。ELISA法測定各時間點血漿HMGB1、IFN-γ及IL-4濃度,通過IFN-γ與IL-4濃度的比值反映Th1/Th2細胞因子平衡的情況,評估兩組機體免疫功能的變化差異,通過HMGB1濃度值比較手術(shù)前后兩組HMGB1濃度的變化,CCK-8法進行PHA誘導(dǎo)的淋巴細胞增殖試驗,流式Annexin V-PI雙染法進行淋巴細胞凋亡檢測。 研究結(jié)果： 1、兩組病人年齡、體重等無統(tǒng)計學(xué)差異(p0.05)； 2、相比于術(shù)前24h,與C組比較,L組術(shù)后oh(0.448±0.139vs.0.352±0.112OD)及術(shù)后48h(0.420±0.094vs.0.326±0.141OD) PHA誘導(dǎo)的淋巴細胞增殖試驗中淋巴細胞活性下降減少(p0.05)； 3、流式Annexin V-PI雙染法進行淋巴細胞凋亡檢測,兩組淋巴細胞凋亡比例在術(shù)后都有所增加,與C組相比,L組術(shù)后48h淋巴細胞凋亡上升幅度較低(3.560±0.775vs.4.173±0.779%),差異有統(tǒng)計學(xué)意義(p0.05)； 4、與C組比較,L組術(shù)后48hIFN-y的濃度(4.041±0.230vs.3.782±0.282pg/ml)升高,差異有統(tǒng)計學(xué)意義(p0.05)；分別計算兩組IFN-y/IL-4的比值,與C組比較,L組比值升高(0.676±0.288vs.0.489±0.124,p0.05)； 5、與C組比較,L組術(shù)后48h的HMGB1表達濃度下降更明顯(53.458±8.983vs.59.387±5.025μg/L),差異有統(tǒng)計學(xué)意義(p0.05)。 研究結(jié)論： 1、圍術(shù)期靜脈輸注利多卡因可減輕手術(shù)創(chuàng)傷對淋巴細胞增殖能力的抑制作用； 2、圍術(shù)期靜脈輸注利多卡因可減少淋巴細胞術(shù)后凋亡； 3、圍術(shù)期靜脈輸注利多卡因可抑制機體免疫調(diào)節(jié)平衡向Th2漂移,保護機體免疫功能； 4、圍術(shù)期靜脈輸注利多卡因?qū)C體免疫功能的調(diào)節(jié)作用可能與其能下調(diào)高遷移率族蛋白B1(HMGB1)的表達有關(guān)。 研究意義： 本研究通過觀察靜脈輸注利多卡因?qū)C體免疫系統(tǒng)的影響,一方面驗證了利多卡因的抗炎作用,為臨床應(yīng)用利多卡因提供理論依據(jù)：一方面提出了利多卡因?qū)C體免疫功能的保護作用可能是通過其抑制晚期炎癥因子高遷移率族蛋白B1(HMGB1)來實現(xiàn)的假設(shè),為臨床抗炎治療提供了新思路,但這一假設(shè)的確切機制尚未明確,還待進一步的深入研究。
[Abstract]:Research background and purpose:
Surgical trauma and the endocrine system of the hypothalamic pituitary adrenal axis (HPA) function enhancement, enhanced responses to stress response of the sympathetic nervous system and acute stress, triggering the body's inflammatory response and systemic inflammatory response syndrome, this process is accompanied by the activation of the immune system, proinflammatory mediators a processing and release of high levels, resulting in rapid inhibition of immune function, and immune suppression caused the effect of surgical stress, is an important cause of infection and accelerate the transfer of residual tumor after surgery. Lidocaine is a kind of common amide local anesthetics, not only has analgesic, anti hyperalgesia, anti arrhythmia research shows that the effect also has anti-inflammatory effect, and perioperative intravenous infusion of lidocaine can reduce postoperative pain, reduce opioid analgesic usage, relieve inflammation In response, accelerate the recovery of gastrointestinal function and shorten the hospitalization time. High mobility group protein B1 (HMGB1) abnormal expression in a variety of malignant tumors, as a late inflammatory protein, has been shown to mediate the inflammatory response to infection and injury, so as to promote the occurrence and development of inflammatory reaction this study. Through continuous intravenous injection of small dose of lidocaine on apoptosis of lymphocyte proliferation were observed, Th1/Th2 drift effects and released by HMGB1, this study was designed to investigate the protective effect and mechanism of immunity of surgical trauma, and provide a theoretical basis for the clinical application of lidocaine anti-inflammatory treatment.
Research methods:
From June 2013 to January 2014 has been diagnosed with cervical cancer in Qilu Hospital of Shandong University and the first operation room undergoing radical hysterectomy under general anesthesia (hysterectomy and pelvic lymphadenectomy) in 30 patients, all patients signed informed consent to medical tests, using the random number table method, the patients were randomly divided into control group (C) and lidocaine group (L), 15 cases in each group (n=15), no significant difference between the two groups of patients with clinical baseline. Tracheal intubation anesthesia. The patient into the operating room after open special lidocaine intravenous access, 15min before induction of anesthesia (intravenous lidocaine 1.5mg/kg injection duration is about 10min), 1.5mg injection of lidocaine anesthesia kg-1 H-1 to the patients with micro pump intravenous induction after leaving the operating room. The control group received equal volume normal saline. 24h before surgery, Oh after surgery, 48h after surgery were selected with static 10ml. vein blood centrifugation, plasma was collected, separation of peripheral blood lymphocyte.ELISA method for determination of plasma HMGB1 at each time point, IFN- y and IL-4 concentration, reflecting Th1/Th2 cytokine balance by the ratio of IFN- gamma and IL-4 concentration changes, assessment of two groups of immune function, the value changes compared before and after the operation of two groups of HMGB1 concentration through the method of CCK-8 HMGB1 concentration, PHA induced lymphocyte proliferation test, lymphocyte apoptosis were detected by flow cytometry with Annexin V-PI double staining method.
The results of the study:
1, there was no statistical difference in age and weight between the two groups (P0.05).
2, compared with preoperative 24h, compared with group C, the activity of lymphocytes in group L decreased (P0.05) after Oh (0.448 + 0.139vs.0.352 + 0.112OD) and 48h (0.420 + 0.094vs.0.326 + 0.141OD) PHA induced lymphocyte proliferation test.
3, the apoptosis rate of lymphocytes was detected by flow Annexin V-PI double staining. The proportion of lymphocyte apoptosis increased in two groups after operation. Compared with C group, the apoptosis rate of 48h lymphocyte in L group increased significantly (3.560 + 0.775vs.4.173 + 0.779%), the difference was statistically significant (P0.05).
4, compared with group C, the concentration of 48hIFN-y in group L increased (4.041 + 0.230vs.3.782 + 0.282pg/ml), and the difference was statistically significant (P0.05). The ratio of IFN-y/IL-4 in the two groups was calculated. Compared with C group, the ratio of L group increased (0.676 + 0.288vs.0.489 + 0.124, P0.05).
5, compared with the C group, the HMGB1 expression concentration of 48h in group L decreased significantly (53.458 + 8.983vs.59.387 + 5.025 g/L), and the difference was statistically significant (P0.05).
The conclusions are as follows:
1, intravenous infusion of lidocaine during perioperative period can reduce the inhibitory effect of surgical trauma on the proliferation of lymphocyte.
2, intravenous infusion of lidocaine during perioperative period can reduce apoptosis after lymphocyte operation.
3, intravenous infusion of lidocaine during perioperative period can inhibit the shift of immunoregulation balance to Th2 and protect the immune function of the body.
4, the regulation of intravenous infusion of lidocaine on the immune function of the body may be related to the ability to reduce the expression of high mobility group protein B1 (HMGB1).
Research significance:
This study observed the effects of intravenous infusion of lidocaine on the immune system, verify the anti-inflammatory effect of lidocaine on the one hand, to provide a theoretical basis for the clinical application of lidocaine: on the one hand, put forward the protective effect of lidocaine on immune function may be through the inhibition of late inflammatory factor of high mobility group protein B1 (HMGB1) to achieve that provides a new idea for clinical anti-inflammatory treatment, but the exact mechanism of this hypothesis is not yet clear, still needs further research.

【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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