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
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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)


Effects and mechanisms of simvastatin pretreatment on liver function in hepatocellular carcinoma(HCC) patients undergoing Pringle’s hepatectomy
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    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。

    Abstract:

    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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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(自然科学版),2020,(9):1338-1343

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  • 收稿日期:2020-04-19
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  • 在线发布日期: 2020-09-30
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