帕瑞昔布对右肝切除患者肝脏缺血再灌注后血清炎症介质水平的影响

发布时间：2018-03-25 19:07

本文选题：帕瑞昔布　切入点：右肝切除术　出处：《吉林大学》2017年硕士论文

【摘要】：目的:肝脏缺血再灌注损伤(hepatic ischemia-reperfusion injury,HIRI)是一种常见的病理生理过程,这其中涉及到了非常复杂的机制。严重的HIRI可引起肝脏及肺、肾等其他远隔器官功能的衰竭。因此对肝癌手术患者采取有效措施以最大程度减轻肝门阻断及肝门开放后引起的缺血再灌注损伤意义重大。本研究拟探讨帕瑞昔布对右肝切除术患者肝脏缺血再灌注后血清炎性介质水平的影响及其部分机制,为临床用药提供参考。方法:明确诊断为肝细胞型肝癌的患者于我院行右肝切除术40例,年龄35~65岁,体重指数(body mass index,BMI)18.0~25.0,ASA(American Society of Anesthesiologists,ASA)分级Ⅱ或Ⅲ级。入组患者肝功能Child-Pugh评分7分(分级为A级)。随机将其分为2组(n=20):帕瑞昔布组(P组)和对照组(C组)。所有患者术前禁水、禁食6h。分别在术前12h与麻醉诱导前,P组以帕瑞昔布40mg溶于10ml生理盐水静脉注射,C组给以同样方式静注10ml生理盐水。入室后开放静脉通路,常规监测心电图(electrocardiogram,ECG)、血压(blood pressure,BP)、脉搏血氧饱和度(saturation of blood oxygen,Sp O2)和脑电双频指数(bispectral index,BIS)监测麻醉深度。两组患者均在局麻下行左侧桡动脉和右侧颈内静脉穿刺并置管以分别监测有创动脉血压和中心静脉压(central venous pressure,CVP)。麻醉诱导:两组患者均依次静脉注射咪达唑仑0.03mg/kg,顺式阿曲库铵0.15mg/kg,芬太尼2~4μg/kg及丙泊酚1.5~2.0mg/kg,待患者意识消失、睫毛反射消失后给予面罩给氧去氮,五分钟后行气管插管,确认气管导管进入气管并选择合适深度后妥善固定,连接麻醉机行机械通气(潮气量8~10 ml/kg、呼吸频率12次/min、吸呼比1:1.5、氧流量2L/min),维持呼气末二氧化碳分压(end-tidal partial pressure of carbon dioxide,PETCO2)35~40mm Hg。麻醉维持:两组患者术中丙泊酚以4~6mg/kg/h的速度持续输注,间断静注芬太尼、顺式阿曲库铵维持麻醉,并随时调整丙泊酚输注速度,维持BIS值40~50。必要时静注相关血管活性药物,维持心率和血压波动幅度在基础值20%内。于麻醉诱导前(T0)、肝门开放时(T1)、缺血再灌注后1h(T2)、6h(T3)、24h(T4)、48(T5)6个时相点经颈内静脉导管抽取静脉血3~5ml,测定血清中天门冬氨酸氨基转移酶(aspartate transaminase,AST)和谷氨酸氨基转移酶(alanine aminotransferase,ALT)的含量;采用ELISA法测定血清中α-肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-6和IL-10的浓度。数据采用SPSS22.0统计软件进行分析,计量资料以均数±标准差(x±s)表示,组内比较采用配对t检验,组间比较采用两独立样本t检验,计数资料比较采用χ2检验,P0.05认为差异具有统计学意义。结果:两组患者年龄、性别比、BMI、肿瘤直径、肝门阻断时间、出血量、手术用时等一般情况比较均无统计学差异(P0.05)。两组患者在麻醉诱导前ALT、AST、TNF-α、IL-6和IL-10等指标的差异无统计学意义(P0.05)。两组患者血液中ALT、AST、TNF-α、IL-6浓度在肝门开放以后的各个时间点均显著高于麻醉诱导前水平(P0.05);P组患者在开放肝门后各时相点血清中的ALT、AST水平均明显低于同一时间点C组患者(P0.05);P组患者在肝门开放后各时点血清中的TNF-α、IL-6水平均明显低于同一时间点C组患者。两组患者T1时刻血清中IL-10水平相比于T0无显著差异(P0.05);在T2-5各个时间点,两组患者血清中IL-10水平相比于T0、T1时刻显著升高,差异有统计学意义(P0.05);P组患者血清IL-10水平显著高于T2-5同一时间点于C组水平,差异有统计学意义(P0.05)结论:帕瑞昔布对右肝部分切除术中肝脏缺血再灌注损伤具有一定程度的保护作用,机制可能与其抑制炎症介质过度释放有关。
[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.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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