入肝血流阻断对肝脏和胰腺功能的影响：87例临床观察及SD大鼠模型研究
发布时间：2018-08-16 07:43
【摘要】：目的:在临床和动物实验的基础上,观察阻断第一肝门对术后血清转氨酶和淀粉酶的影响,并对其机制做进一步的探讨。方法:首先回顾性分析我院肝胆外科2013年1月至2015年6月采用阻断第一肝门进行肝切除的247例患者临床资料,根据入组标准:(1)肝功能Child-Pugh分级A级或B级经短期治疗改善至A级;(2)术前血清淀粉酶正常(0~220 U/L),无胰腺炎病史、无胆石病患者;(3)阻断肝脏血流方法为第一肝门(Pringle法),每次阻断最长时间为20min,间歇松开5min;(4)一般情况良好无明显心、肺、肾等重要脏器的病变;(5)术后未行护肝、抑酶治疗;(6)所有患者术前和术后的检查资料完整。有87例患者符合入组要求,其中男68例,女19例,年龄18~69岁,平均48岁。术后病理:肝海绵状血管瘤2例;胆管细胞癌3例;肝炎症性坏死1例;肝细胞癌81例。对临床数据做初步分析阻断第一肝门对肝功能和术后淀粉酶的影响,然后设计动物实验对临床数据进行验证和探讨。选取70只雄性SD大鼠随机分配为对照组(A)10只,持续阻断组(B)30只,间歇阻断组(C)30只。持续阻断组大鼠持续阻断肝门45分钟;间歇阻断组分次阻断肝门,每次阻断15分钟,间歇5分钟,共阻断3次;对照组不做任何处理。分别在术后第一、二、三天从持续阻断组和间歇阻断组中每天各取10只(亚组,B1,B2,B3和C1,C2,C3,每组10只)抽取门静脉血,测定血清淀粉酶和ALT、AST。同上,分别在各时段取大鼠肝中叶和胰腺组织,用甲醛固定制做HE染色切片,光镜下观察病理学变化。同时取部分胰腺组织,用戊二醛固定,电镜下观察组织细胞器水平变化。结果:临床数据分析得出肝切除术后第一天转氨酶较术前显著升高,差异有统计学意义(P0.05);部分患者术后第一天出现高淀粉酶血症,发生率为19.5%,且高淀粉酶血症与阻断第一肝门的次数有关(P0.05)。动物实验血生化结果显示,术后第一天血清淀粉酶水平持续阻断组和间歇阻断组较对照组显著升高(持续阻断组:2437.6±589.3 U/Lvs 909±221.9 U/L,P0.05,间歇阻断组:1858.5±579.7 U/Lvs 909±221.9 U/L,P0.05),且持续阻断组高于间歇阻断组(2437.6±589.3 U/Lvs1858.5±579.7 U/L,P0.05);术后第一天血清ALT持续阻断组和间歇阻断组较对照组明显升高(持续阻断组:453.2±163.9 U/L vs65.4±13.1 U/L,P0.05;间歇阻断组:199.4±80.5 U/L vs65.4±13.1 U/L,P0.05),同样持续阻断组高于间歇阻断组(453.2±163.9 U/L vs199.4±80.5 U/L,P0.05);术后第一天血清AST持续阻断组和间歇阻断组较对照组显著升高(持续阻断组:628.4±69.2U/Lvs118.8±15.9 U/L,P0.05;间歇阻断组:430.2±133.0 U/Lvs118.8±15.9U/L,P0.05),以持续阻断组高于间歇阻断组(628.4±69.2 U/Lvs430.2±133.0 U/L,P0.05)。在肝脏和胰腺组织MDA结果中:术后第一天肝脏组织MDA表达量持续阻断组和间歇阻断组显著高于对照组(持续阻断组:3.63±1.89 nmol/mgprotvs0.98±0.25 nmol/mgprot,P0.05;间歇阻断组1.87±0.46 nmol/mgprotvs0.98±0.25 nmol/mgprot,P0.05),且持续阻断高于间歇阻断组(3.63±1.89 nmol/mgprotvs1.87±0.46 nmol/mgprot,P0.05);术后第二天持续阻断组显著高于间歇阻断组(2.71±0.81 nmol/mgprotvs1.49±0.61nmol/mgprot,P0.05)。术后第一天胰腺组织MDA表达量持续阻断组显著高于对照组(1.23±0.75 mgprotvs0.58±0.31 mgprot,P0.05),且持续阻断组高于间歇阻断组(1.23±0.75 mgprotvs0.51±0.28 mgprot,P0.05);术后第二天持续阻断组高于间歇阻断组(0.99±0.31 mgprotvs0.71±0.26 mgprot,P0.05)。在肝脏和胰腺组织SOD结果中:术后第一天肝脏组织SOD表达量持续阻断组和间歇阻断组均显著低于对照组(持续阻断组:93.58±15.95 U/Lvs190.1±15.8 U/L,P0.05;间歇阻断组:111.57±14.11U/L vs190.1±15.8 U/L,P0.05),且持续阻断组显著低于间歇阻断组(93.58±15.95 U/Lvs111.57±14.11 U/L,P0.05);术后第二天和第三天SOD表达量持续阻断组均显著低于间歇阻断组(术后第二天:102.7±22.89U/Lvs147.67±20.91 U/L,P0.05;术后第三天:116.77±32.4 U/Lvs146.77±27.4 U/L,P0.05);术后第一天胰腺组织SOD表达量持续阻断组和间歇阻断组较对照组明显降低(持续阻断组:85.4±38.1 U/Lvs 257.51±43.1U/L,P0.05;间歇阻断组:145.5±75.1 U/Lvs 257.51±43.1 U/L,P0.05),且持续阻断组显著低于间歇阻断组(85.4±38.1 U/Lvs145.5±75.1 U/L,P0.05),术后第二天持续阻断组较间歇阻断明显降低(118.13±44.01 U/Lvs176.54±36.84 U/L,P0.05)。胰腺组织HE染色,对照组胰腺组织内分泌腺、外分泌腺细胞排列正常,无病理改变。持续阻断组和间歇阻断组都有明显的病理学变化,且在术后第一天最为严重。光镜下看到有少量胰腺细胞坏死,肿胀,空泡状改变,并有炎症细胞浸润和少量的出血,以持续阻断肝门后最重。肝脏组织经HE染色后,光镜下观察对照组无明显的病理学改变。持续阻断组肝细胞出现大量适应性改变(包括细胞萎缩、增生和凝结),不同类型的变性、坏死,炎性细胞浸润,并且同样以术后第一天最重,间歇阻断组病理性改变较轻。术后第三天可见到再生的肝细胞和纤维化。电镜下发现持续阻断组胰腺的外分泌腺细胞的内质网和线粒体轻度肿胀,间歇阻断组没发现明显病理改变。结论:(1)阻断第一肝门后血清转氨酶和淀粉酶升高,可能与肝脏缺血在灌注损伤和胰腺的淤血损伤有关。(2)间歇阻断肝门比持续阻断肝门对肝脏和胰腺的损伤有较好的耐受性。
[Abstract]:Objective:To observe the effect of blocking the first hepatic porta on serum aminotransferase and amylase after hepatectomy on the basis of clinical and animal experiments,and to further explore the mechanism.Methods:The clinical data of 247 patients who underwent hepatectomy by blocking the first hepatic porta from January 2013 to June 2015 in the Department of Hepatobiliary Surgery of our hospital were retrospectively analyzed. Group criteria: (1) Child-Pugh grade A or B liver function improved to grade A after short-term treatment; (2) preoperative serum amylase normal (0-220 U/L), no history of pancreatitis, no gallstone disease; (3) blockade of liver blood flow method for the first porta hepatis (Pringle method), each blockade for 20 minutes, intermittent relaxation for 5 minutes; (4) in general good without obvious heart, Lung, kidney and other important organs lesions; (5) postoperative liver protection, inhibition of enzyme treatment; (6) all patients before and after the examination data integrity. 87 patients met the inclusion requirements, including 68 males, 19 females, age 18-69 years, average 48 years. Postoperative pathology: hepatic cavernous hemangioma 2 cases; cholangiocarcinoma 3 cases; hepatic inflammatory necrosis 1 case; hepatocellular carcinoma 81 cases. Seventy male SD rats were randomly divided into control group (A), continuous blockade group (B), intermittent blockade group (C) and continuous blockade group (B), respectively. The control group did not receive any treatment. Ten portal vein blood samples (subgroups, B1, B2, B3 and C1, C2, C3, 10 in each group) were taken daily from the continuous occlusion group and the intermittent occlusion group on the first, second and third days after operation, respectively. Serum amylase and ALT, AST. At the same time, some pancreatic tissues were fixed with glutaraldehyde, and the level of organelles was observed under electron microscope. Results: The transaminase level in the first day after hepatectomy was significantly higher than that before hepatectomy. The incidence of hyperamylasemia was 19.5% in some patients on the first day after operation, and hyperamylasemia was related to the times of blocking the first hepatic hilum (P 0.05). Continuous block group: 2437.6 65 The levels of serum AST in the intermittent blockade group were significantly higher than those in the intermittent blockade group (628.4+692 U/Lvs118.8) on the first day after operation. The expression of MDA in liver and pancreas tissues on the first day after operation was significantly higher than that in the control group (628.4 +69.2 U/Lvs 430.2 +133.0 U/L, P 0.05). Group: 3.63 + 1.89nmol / mgprotvs 0.98 + 0.25 nmol / mgprotv 0.98 [/mgprotv 0.98 + 0.25 nmol / mgprotv 0.98 + 0.25 nmol / mgprotv 0.98 [/mgprotv 0.98 [/mgprotv 0.25 nmol / mgprot, P 0.05, P 0.05, 3.63 + 1.89nmol / mgprotvs 1.98 [/mgprotvs 1.87 + 0.87 + 0.46 nmol / mgprotv 1.46 nmol / mgprotv 0.05, P 0.05, 0.05, 0.05, 1.87 [/mgprotv 0.87 [/mgprotv 0.In the meantime, it is necessary to study the relationship between the two. The expression of MDA in pancreatic tissue was significantly higher in the first day after operation than in the control group (1.23.75 mgprotvs 0.58.31 mgprot, P 0.05), and higher in the continuous block group than in the intermittent block group (1.23.75 mgprotvs 0.51.28 mgprot, P 0.05), and higher in the second day after operation than in the intermittent block group (0.99.31 mgprot, P 0.05). Rotvs 0.71 (+ 0.26 mgprot, P 0.05). In the results of SOD in liver and pancreas tissues, the expression of SOD in the first day after operation was significantly lower than that in the control group (93.58 (+ 15.95 U / Lvs 190.1 (+ 15.8 U / L, P 0.05); and in the intermittent blocking group, 111.57 (+ 14.11 U / Lvs 190.1 (+ 15.8 U / L), P 0.05). The expression of SOD in the two groups was significantly lower than that in the intermittent group (93.58 Compared with the control group, the expression level in the continuous block group and the intermittent block group was significantly lower (85.4 65507 HE staining of pancreatic tissue showed that the endocrine glands and exocrine gland cells in the control group were normal without pathological changes. Cell necrosis, swelling, vacuolar changes, inflammatory cell infiltration and a small amount of hemorrhage were the most serious after continuous blockade of the hepatic hilum. Necrosis, infiltration of inflammatory cells, and also the most severe on the first day after surgery, the pathological changes were mild in the intermittent blocking group. Regenerated hepatocytes and fibrosis were seen on the third day after surgery. (1) The elevation of serum aminotransferase and amylase after hepatic portal occlusion may be related to hepatic ischemia perfusion injury and pancreatic congestion injury. (2) Intermittent hepatic portal occlusion is more tolerant to hepatic and pancreatic injury than continuous hepatic portal occlusion.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R657.3
[Abstract]:Objective:To observe the effect of blocking the first hepatic porta on serum aminotransferase and amylase after hepatectomy on the basis of clinical and animal experiments,and to further explore the mechanism.Methods:The clinical data of 247 patients who underwent hepatectomy by blocking the first hepatic porta from January 2013 to June 2015 in the Department of Hepatobiliary Surgery of our hospital were retrospectively analyzed. Group criteria: (1) Child-Pugh grade A or B liver function improved to grade A after short-term treatment; (2) preoperative serum amylase normal (0-220 U/L), no history of pancreatitis, no gallstone disease; (3) blockade of liver blood flow method for the first porta hepatis (Pringle method), each blockade for 20 minutes, intermittent relaxation for 5 minutes; (4) in general good without obvious heart, Lung, kidney and other important organs lesions; (5) postoperative liver protection, inhibition of enzyme treatment; (6) all patients before and after the examination data integrity. 87 patients met the inclusion requirements, including 68 males, 19 females, age 18-69 years, average 48 years. Postoperative pathology: hepatic cavernous hemangioma 2 cases; cholangiocarcinoma 3 cases; hepatic inflammatory necrosis 1 case; hepatocellular carcinoma 81 cases. Seventy male SD rats were randomly divided into control group (A), continuous blockade group (B), intermittent blockade group (C) and continuous blockade group (B), respectively. The control group did not receive any treatment. Ten portal vein blood samples (subgroups, B1, B2, B3 and C1, C2, C3, 10 in each group) were taken daily from the continuous occlusion group and the intermittent occlusion group on the first, second and third days after operation, respectively. Serum amylase and ALT, AST. At the same time, some pancreatic tissues were fixed with glutaraldehyde, and the level of organelles was observed under electron microscope. Results: The transaminase level in the first day after hepatectomy was significantly higher than that before hepatectomy. The incidence of hyperamylasemia was 19.5% in some patients on the first day after operation, and hyperamylasemia was related to the times of blocking the first hepatic hilum (P 0.05). Continuous block group: 2437.6 65 The levels of serum AST in the intermittent blockade group were significantly higher than those in the intermittent blockade group (628.4+692 U/Lvs118.8) on the first day after operation. The expression of MDA in liver and pancreas tissues on the first day after operation was significantly higher than that in the control group (628.4 +69.2 U/Lvs 430.2 +133.0 U/L, P 0.05). Group: 3.63 + 1.89nmol / mgprotvs 0.98 + 0.25 nmol / mgprotv 0.98 [/mgprotv 0.98 + 0.25 nmol / mgprotv 0.98 + 0.25 nmol / mgprotv 0.98 [/mgprotv 0.98 [/mgprotv 0.25 nmol / mgprot, P 0.05, P 0.05, 3.63 + 1.89nmol / mgprotvs 1.98 [/mgprotvs 1.87 + 0.87 + 0.46 nmol / mgprotv 1.46 nmol / mgprotv 0.05, P 0.05, 0.05, 0.05, 1.87 [/mgprotv 0.87 [/mgprotv 0.In the meantime, it is necessary to study the relationship between the two. The expression of MDA in pancreatic tissue was significantly higher in the first day after operation than in the control group (1.23.75 mgprotvs 0.58.31 mgprot, P 0.05), and higher in the continuous block group than in the intermittent block group (1.23.75 mgprotvs 0.51.28 mgprot, P 0.05), and higher in the second day after operation than in the intermittent block group (0.99.31 mgprot, P 0.05). Rotvs 0.71 (+ 0.26 mgprot, P 0.05). In the results of SOD in liver and pancreas tissues, the expression of SOD in the first day after operation was significantly lower than that in the control group (93.58 (+ 15.95 U / Lvs 190.1 (+ 15.8 U / L, P 0.05); and in the intermittent blocking group, 111.57 (+ 14.11 U / Lvs 190.1 (+ 15.8 U / L), P 0.05). The expression of SOD in the two groups was significantly lower than that in the intermittent group (93.58 Compared with the control group, the expression level in the continuous block group and the intermittent block group was significantly lower (85.4 65507 HE staining of pancreatic tissue showed that the endocrine glands and exocrine gland cells in the control group were normal without pathological changes. Cell necrosis, swelling, vacuolar changes, inflammatory cell infiltration and a small amount of hemorrhage were the most serious after continuous blockade of the hepatic hilum. Necrosis, infiltration of inflammatory cells, and also the most severe on the first day after surgery, the pathological changes were mild in the intermittent blocking group. Regenerated hepatocytes and fibrosis were seen on the third day after surgery. (1) The elevation of serum aminotransferase and amylase after hepatic portal occlusion may be related to hepatic ischemia perfusion injury and pancreatic congestion injury. (2) Intermittent hepatic portal occlusion is more tolerant to hepatic and pancreatic injury than continuous hepatic portal occlusion.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R657.3
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