文章摘要
杨文杰,张 峰,成 峰,饶建华,游 伟.辛伐他汀预处理对Pringle手法肝细胞癌切除术后肝功能的影响及机制[J].南京医科大学学报,2020,(9):1338~1343
辛伐他汀预处理对Pringle手法肝细胞癌切除术后肝功能的影响及机制
Effects and mechanisms of simvastatin pretreatment on liver function in hepatocellular carcinoma(HCC) patients undergoing Pringle’s hepatectomy
投稿时间:2020-04-19  
DOI:10.7655/NYDXBNS20200916
中文关键词: 辛伐他汀  Pringle手法  炎症反应  氧化应激反应  内质网应激
英文关键词: simvastatin  Pringle maneuver  inflammatory reaction  oxidative stress reaction  endoplasmic reticulum stress
基金项目:国家自然科学基金(81871259,81400650);江苏省“六大人才高峰”高层次人才项目(WSW?019)
作者单位
杨文杰 南京医科大学第一附属医院肝胆中心/肝移植中心江苏 南京 210029 
张 峰 南京医科大学第一附属医院肝胆中心/肝移植中心江苏 南京 210029 
成 峰 南京医科大学第一附属医院肝胆中心/肝移植中心江苏 南京 210029 
饶建华 南京医科大学第一附属医院肝胆中心/肝移植中心江苏 南京 210029 
游 伟 南京医科大学第一附属医院肝胆中心/肝移植中心江苏 南京 210029 
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中文摘要:
      目的:探讨辛伐他汀(simvastatin)预处理对Pringle手法肝细胞癌切除术后肝功能的影响及其机制。方法:73例肝细胞癌患者随机分为对照组(n=35)和Simvastatin组(simvastatin预处理,n=38,患者术前3 d按20 mg/d口服simvastatin)。分别于手术开腹后和关腹前收集部分肝组织作为标本,于术前和术后第1天采集患者血清。测定血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBIL)和白蛋白(albumin,ALB)以评估肝细胞损伤;逆转录聚合酶链反应(RT?PCR)分析炎症因子白细胞介素(interleukin,IL)?1、IL?6、诱导型一氧化氮合酶(inducible nitric oxide synthase,INOS)及肿瘤坏死因子(tumor necrosis factor,TNF)?α水平。试剂盒检测血清丙二醛(malondialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)水平;Western blot检测内质网应激蛋白(C/EBP?homologous protein,CHOP)水平。结果:Simvastatin组术后第1天血清ALT、AST和TBIL水平显著低于对照组(P < 0.05);RT?PCR提示Simvastatin组IL?1、IL?6、INOS及TNF?α水平较对照组明显降低(P < 0.05)。Simvastatin组血清MDA水平明显低于对照组(P < 0.05);SOD水平显著高于对照组(P < 0.05)。Western blot显示Simvastatin组CHOP表达水平较对照组减少。结论:对于肝细胞癌患者,辛伐他汀预处理可有效缓解Pringle手法肝部分切除术后的肝功能损伤,机制可能与抑制氧化应激和内质网应激水平有关。
英文摘要:
      Objective:This study aims to investigate effects and mechanisms of simvastatin pretreatment on liver function in HCC patients undergoing Pringle’s hepatectomy. Methods:Total 73 HCC patients were randomly divided into control group(n=35)and simvastatin pretreatment group(patients were given oral simvastatin 20 mg/d,n=38). Pre?hepatectomy hepatic biopsies were harvested after laparotomy(prior to hepatic portal occlusion),and post?hepatectomy hepatic biopsies were obtained after reperfusion(prior to abdominal closure). Serum was collected before operation(Pre?Op)and on the first day after operation(POD?1). Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and albumin(ALB)were measured to evaluate liver injury,and the levels of inflammatory cytokines interleukin(IL)?1,IL?6,inducible nitric oxide synthase(INOS)and tumor necrosis factor(TNF)?α were analyzed by reverse transcriptase polymerase chain reaction(RT?PCR). The levels of serum malondialdehyde(MDA) and superoxide dismutase(SOD) were detected by kits according to the manufacturer’s directions. Endoplasmic reticulum stress?related protein C/EBP?homologous protein(CHOP) was analyzed by Western blot. Results:The serum levels of ALT,AST and TBIL in POD?1 were significantly lower in simvastatin group than those in control group(P < 0.05),and RT?PCR results showed the levels of IL?1,IL?6,INOS and TNF?α, were significantly lower in simvastatin group than those in control group(P < 0.05). Furthermore,serum MDA was lower in simvastatin group than that in control group(P < 0.05);SOD in simvastatin group was significantly higher than that in control group(P < 0.05). Western blot results displayed that the expression of CHOP was lower in simvastatin group than in control group. Conclusion:Simvastatin pretreatment for HCC patient effectively alleviates liver injury after Pringle’s hepatectomy,and its mechanism could be related to the inhibition of oxidative stress and endoplasmic reticulum stress.
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