發(fā)布時(shí)間：2018-03-25 19:07

  本文選題：帕瑞昔布　切入點(diǎn)：右肝切除術(shù)　出處：《吉林大學(xué)》2017年碩士論文

【摘要】：目的:肝臟缺血再灌注損傷(hepatic ischemia-reperfusion injury,HIRI)是一種常見(jiàn)的病理生理過(guò)程,這其中涉及到了非常復(fù)雜的機(jī)制。嚴(yán)重的HIRI可引起肝臟及肺、腎等其他遠(yuǎn)隔器官功能的衰竭。因此對(duì)肝癌手術(shù)患者采取有效措施以最大程度減輕肝門(mén)阻斷及肝門(mén)開(kāi)放后引起的缺血再灌注損傷意義重大。本研究擬探討帕瑞昔布對(duì)右肝切除術(shù)患者肝臟缺血再灌注后血清炎性介質(zhì)水平的影響及其部分機(jī)制,為臨床用藥提供參考。方法:明確診斷為肝細(xì)胞型肝癌的患者于我院行右肝切除術(shù)40例,年齡35~65歲,體重指數(shù)(body mass index,BMI)18.0~25.0,ASA(American Society of Anesthesiologists,ASA)分級(jí)Ⅱ或Ⅲ級(jí)。入組患者肝功能Child-Pugh評(píng)分7分(分級(jí)為A級(jí))。隨機(jī)將其分為2組(n=20):帕瑞昔布組(P組)和對(duì)照組(C組)。所有患者術(shù)前禁水、禁食6h。分別在術(shù)前12h與麻醉誘導(dǎo)前,P組以帕瑞昔布40mg溶于10ml生理鹽水靜脈注射,C組給以同樣方式靜注10ml生理鹽水。入室后開(kāi)放靜脈通路,常規(guī)監(jiān)測(cè)心電圖(electrocardiogram,ECG)、血壓(blood pressure,BP)、脈搏血氧飽和度(saturation of blood oxygen,Sp O2)和腦電雙頻指數(shù)(bispectral index,BIS)監(jiān)測(cè)麻醉深度。兩組患者均在局麻下行左側(cè)橈動(dòng)脈和右側(cè)頸內(nèi)靜脈穿刺并置管以分別監(jiān)測(cè)有創(chuàng)動(dòng)脈血壓和中心靜脈壓(central venous pressure,CVP)。麻醉誘導(dǎo):兩組患者均依次靜脈注射咪達(dá)唑侖0.03mg/kg,順式阿曲庫(kù)銨0.15mg/kg,芬太尼2~4μg/kg及丙泊酚1.5~2.0mg/kg,待患者意識(shí)消失、睫毛反射消失后給予面罩給氧去氮,五分鐘后行氣管插管,確認(rèn)氣管導(dǎo)管進(jìn)入氣管并選擇合適深度后妥善固定,連接麻醉機(jī)行機(jī)械通氣(潮氣量8~10 ml/kg、呼吸頻率12次/min、吸呼比1:1.5、氧流量2L/min),維持呼氣末二氧化碳分壓(end-tidal partial pressure of carbon dioxide,PETCO2)35~40mm Hg。麻醉維持:兩組患者術(shù)中丙泊酚以4~6mg/kg/h的速度持續(xù)輸注,間斷靜注芬太尼、順式阿曲庫(kù)銨維持麻醉,并隨時(shí)調(diào)整丙泊酚輸注速度,維持BIS值40~50。必要時(shí)靜注相關(guān)血管活性藥物,維持心率和血壓波動(dòng)幅度在基礎(chǔ)值20%內(nèi)。于麻醉誘導(dǎo)前(T0)、肝門(mén)開(kāi)放時(shí)(T1)、缺血再灌注后1h(T2)、6h(T3)、24h(T4)、48(T5)6個(gè)時(shí)相點(diǎn)經(jīng)頸內(nèi)靜脈導(dǎo)管抽取靜脈血3~5ml,測(cè)定血清中天門(mén)冬氨酸氨基轉(zhuǎn)移酶(aspartate transaminase,AST)和谷氨酸氨基轉(zhuǎn)移酶(alanine aminotransferase,ALT)的含量;采用ELISA法測(cè)定血清中α-腫瘤壞死因子(tumor necrosis factor-α,TNF-α)、白細(xì)胞介素(interleukin,IL)-6和IL-10的濃度。數(shù)據(jù)采用SPSS22.0統(tǒng)計(jì)軟件進(jìn)行分析,計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,組內(nèi)比較采用配對(duì)t檢驗(yàn),組間比較采用兩獨(dú)立樣本t檢驗(yàn),計(jì)數(shù)資料比較采用χ2檢驗(yàn),P0.05認(rèn)為差異具有統(tǒng)計(jì)學(xué)意義。結(jié)果:兩組患者年齡、性別比、BMI、腫瘤直徑、肝門(mén)阻斷時(shí)間、出血量、手術(shù)用時(shí)等一般情況比較均無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。兩組患者在麻醉誘導(dǎo)前ALT、AST、TNF-α、IL-6和IL-10等指標(biāo)的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。兩組患者血液中ALT、AST、TNF-α、IL-6濃度在肝門(mén)開(kāi)放以后的各個(gè)時(shí)間點(diǎn)均顯著高于麻醉誘導(dǎo)前水平(P0.05);P組患者在開(kāi)放肝門(mén)后各時(shí)相點(diǎn)血清中的ALT、AST水平均明顯低于同一時(shí)間點(diǎn)C組患者(P0.05);P組患者在肝門(mén)開(kāi)放后各時(shí)點(diǎn)血清中的TNF-α、IL-6水平均明顯低于同一時(shí)間點(diǎn)C組患者。兩組患者T1時(shí)刻血清中IL-10水平相比于T0無(wú)顯著差異(P0.05);在T2-5各個(gè)時(shí)間點(diǎn),兩組患者血清中IL-10水平相比于T0、T1時(shí)刻顯著升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05);P組患者血清IL-10水平顯著高于T2-5同一時(shí)間點(diǎn)于C組水平,差異有統(tǒng)計(jì)學(xué)意義(P0.05)結(jié)論:帕瑞昔布對(duì)右肝部分切除術(shù)中肝臟缺血再灌注損傷具有一定程度的保護(hù)作用,機(jī)制可能與其抑制炎癥介質(zhì)過(guò)度釋放有關(guān)。
[Abstract]:Objective: hepatic ischemia reperfusion injury (hepatic ischemia-reperfusion, injury, HIRI) is a common pathophysiological process, which involves very complex mechanisms. HIRI can cause serious liver and lung, kidney and other remote organ dysfunction. So take effective measures for patients with liver cancer surgery due to the maximum to reduce the degree of hepatic portal occlusion and hepatic portal open after ischemia reperfusion injury. This study aims to investigate the effect of serum levels of inflammatory mediators of parecoxib on right hepatectomy after hepatic ischemia reperfusion and its mechanism, to provide reference for clinical medication. Methods: the diagnosis of hepatocellular carcinoma patients in our hospital underwent right hepatic resection in 40 cases, 35~65 years of age, body mass index (body mass index, BMI 18.0~25.0), ASA (American Society of Anesthesiologists, ASA) grade II or III patients of liver. The function Child-Pugh score of 7 (Grade A). They were randomly divided into 2 groups (n=20): parecoxib group (P group) and control group (C group). All patients preoperative fasting water fasting, 6h. respectively before 12h and before induction of anesthesia, P group with parecoxib 40mg in normal saline 10ml intravenous injection, the same way C group received intravenous injection of 10ml saline. After the break open venous access, routine monitoring of electrocardiogram (electrocardiogram, ECG), blood pressure (blood, pressure, BP), pulse oxygen saturation (saturation of blood oxygen, Sp O2) and bispectral index (bispectral, index, BIS) in monitoring the depth of anesthesia. Two patients were in local anesthesia the left radial artery and right internal jugular vein was cannulated to monitor invasive arterial blood pressure and central venous pressure (central venous, pressure, CVP). Anesthesia induction: two groups of patients were followed by intravenous injection of midazolam 0.03mg/kg, cisatracurium 0.15mg/kg, 2~4 g/kg and fentanyl 1.5~2.0mg/kg propofol, after the patients lost consciousness, loss of eyelash reflex after giving mask oxygen to nitrogen, five minutes after tracheal intubation, confirmation of endotracheal tube into the trachea and choose the appropriate depth after proper fixation, connecting the anesthetic machine mechanical ventilation (8~10 ml/kg tidal volume, respiratory rate 12 /min breathe oxygen flow ratio 1:1.5, 2L/min), maintain PetCO2 (end-tidal partial pressure of carbon dioxide PETCO2, 35~40mm Hg.): propofol anesthesia in two groups of patients with 4~6mg/kg/h speed continuous infusion, intermittent intravenous fentanyl and cisatracurium maintain anesthesia, and adjust the infusion of propofol speed, to maintain the BIS value of 40~50. when necessary relevant vasoactive drug for intravenous injection, maintain the blood pressure and heart rate fluctuations in value 20%. Before induction of anesthesia (T0), portal opening (T1), ischemia reperfusion After the injection of 1H (T2), 6h (T3), 24h (T4), 48 (T5) 6 phases of internal jugular vein catheter venous blood 3~5ml, serum aspartate aminotransferase (aspartate, transaminase, AST) and alanine aminotransferase (alanine aminotransferase, ALT) content; Determination of tumor necrosis factor alpha in serum by the method of ELISA (tumor necrosis factor- TNF- alpha, alpha), interleukin (interleukin, IL) concentration of -6 and IL-10. SPSS22.0 software was used for statistical analysis, measurement data to mean + standard deviation (x + s) said the group compared with the paired t test, comparison between groups using two independent samples t test, count data were compared using the 2 test, P0.05 considered statistically significant. Results: two groups of patients with age, sex ratio, BMI, diameter of tumor, hepatic portal occlusion time, bleeding volume, operation time in general were no statistically significant difference (P0.05 two). Patients in group ALT before induction of anesthesia, AST, TNF- alpha, there were no significant differences between IL-6 and IL-10 index (P0.05). Two groups of patients with blood ALT, AST, TNF- alpha, each time point after hepatic portal open IL-6 concentration were significantly higher than the level before induction of anesthesia (P0.05); P group in the open portal at each time point in the serum ALT, AST levels were significantly lower than the same time point in C group (P0.05); TNF- alpha in serum at different time points after the opening of the portal in P group, IL-6 was significantly lower than that of the same time point in C group. Compared with IL-10 levels in the two groups the moment of T1 in serum in T0 patients had no significant difference (P0.05); T2-5 at each time point, the levels of IL-10 in two patients were compared to the T0, T1 increased significantly, the difference was statistically significant (P0.05); IL-10 level of serum P was significantly higher than that of T2-5 at the same time point in group C, there were significant differences (P0.05). Theory: parecoxib on partial right hepatectomy of liver protective effect of ischemia reperfusion injury to a certain extent, the mechanism may be related to the inhibition of excessive release of inflammatory mediators.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R614

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