氢饱和生理盐水在重症急性胰腺炎肝损伤中的抗氧化应激作用及对丝裂原活化蛋白激酶通路的影响
경포화생리염수재중증급성이선염간손상중적항양화응격작용급대사렬원활화단백격매통로적영향
Anti-oxidative stress role of hydrogen-rich saline and its effect of mitogen-activated protein kinases pathway on hepatic injury of severe acute pancreatitis
  • 万方数据
    中华实验外科杂志 중화실험외과잡지
    CHINESE JOURNAL OF EXPERIMENTAL SURGERY
    2015年 1期 33-36 ,共4页

    殷涛%石乔%郭闻一%陈辰%赵亮%阿布克力木%孙荣泽%梅方超%李晨

    은도%석교%곽문일%진신%조량%아포극력목%손영택%매방초%리신

    胰腺炎%氢饱和生理盐水%肝损伤%氧化应激%丝裂原活化蛋白激酶 胰腺炎%氫飽和生理鹽水%肝損傷%氧化應激%絲裂原活化蛋白激酶
    이선염%경포화생리염수%간손상%양화응격%사렬원활화단백격매
    Pancreatitis%Hydrogen-rich saline%Hepatic injury%Oxidative stress%Mitogen-activated protein kinases
    目的 观察氢饱和生理盐水(HRS)对于急性坏死性胰腺炎(ANP)大鼠肝脏活性氧自由基(ROS)激活的丝裂原活化蛋白激酶(MAPKs)通路的影响,并探讨其对于ANP大鼠肝脏的保护作用.方法 90只雄性Wistar大鼠随机分为假手术(SO)组、ANP组和HRS组,每组分为3、12、24h3个亚组(n=10).逆行胆胰管注射5％牛磺胆酸钠制备ANP模型,SO组仅开腹翻动胰十二指肠后关腹.HRS组术后尾静脉补充HRS 6 ml/kg,同时皮下注射HRS 20 ml/kg,其余各组同等剂量给予生理盐水.术后分组剖杀,检测血清血淀粉酶(AMY)、脂肪酶(LIP)、谷丙转氨酶(ALT)及谷草转氨酶(AST).取胰头及肝组织固定切片,观察病理改变并评分或分级,免疫组织化学检测肝脏组织中磷酸化c-jun氨基端激酶(p-JNK)、p-p38及磷酸化细胞外信号调节激酶(p-ERK)表达.检测新鲜肝脏组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)水平.结果 各时间点ANP大鼠血清AMY(U/L)(5 385±572比1 146±121)、LIP(U/L)(1 924.9±105.4比86.5±8.9)、ALT (U/L)(156.9±15.8比56.1±5.4)、AST (U/L)(448.5±53.0比124.6±14.7)以及胰腺肝脏病理评分[(13.79±1.36)比(0.38±0.53)分]较SO组均显著升高,差异有统计学意义(P＜0.05);HRS组AMY(U/L)(5 567±512比5 385 ±572)、LIP (U/L)(1 856.8±149.3比1 924.9±105.4)较ANP组下降,但差异无统计学意义(P＞0.05).HRS组ALT(U/L)(134.8±11.8比156.9±15.8)、AST(U/L)(326.6±20.5比448.5±53.0)及肝脏的病理分级(17.1比23.1)较ANP组有显著降低,差异有统计学意义(P＜0.05);ANP组肝脏组织SOD(U/mg)(127.2±11.6比267.4±33.2)活性水平较SO组有明显降低,MDA (nmol/mg)(12.6±3.1比3.9±1.7)水平明显升高,差异有统计学意义(P＜0.05),HRS组肝脏组织中SOD (U/mg)(177.4±12.5比127.2±11.6)活性较ANP组有显著升高,MDA(nmoL/mg)(9.7±2.3比12.6±3.1)含量显著降低,差异有统计学意义(P＜0.05).ANP组肝脏组织中p-JNK(121.40±10.70比2.60±0.45),p-p38(63.1±6.9比16.2±1.7),p-ERK(7.10±1.40比0.90±0.04)水平比较于SO组明显升高,差异有统计学意义(P＜0.05),HRS组p-JNK(51.30±9.70比121.40±10.70)及p-p38(16.2±1.7比63.1±7.0)水平比较于ANP组有显著下降,差异有统计学意义(P＜0.05),但p-ERK(6.70±1.30比7.10±1.40)表达差异无统计学意义(P＞0.05).结论 HRS可有有效的降低ANP大鼠肝脏氧化应激,从而减少ROS对JNK及p38通路的激活,从而对ANP大鼠肝脏起到保护作用.
    목적 관찰경포화생리염수(HRS)대우급성배사성이선염(ANP)대서간장활성양자유기(ROS)격활적사렬원활화단백격매(MAPKs)통로적영향,병탐토기대우ANP대서간장적보호작용.방법 90지웅성Wistar대서수궤분위가수술(SO)조、ANP조화HRS조,매조분위3、12、24h3개아조(n=10).역행담이관주사5％우광담산납제비ANP모형,SO조부개복번동이십이지장후관복.HRS조술후미정맥보충HRS 6 ml/kg,동시피하주사HRS 20 ml/kg,기여각조동등제량급여생리염수.술후분조부살,검측혈청혈정분매(AMY)、지방매(LIP)、곡병전안매(ALT)급곡초전안매(AST).취이두급간조직고정절편,관찰병리개변병평분혹분급,면역조직화학검측간장조직중린산화c-jun안기단격매(p-JNK)、p-p38급린산화세포외신호조절격매(p-ERK)표체.검측신선간장조직중초양화물기화매(SOD)활성급병이철(MDA)수평.결과 각시간점ANP대서혈청AMY(U/L)(5 385±572비1 146±121)、LIP(U/L)(1 924.9±105.4비86.5±8.9)、ALT (U/L)(156.9±15.8비56.1±5.4)、AST (U/L)(448.5±53.0비124.6±14.7)이급이선간장병리평분[(13.79±1.36)비(0.38±0.53)분]교SO조균현저승고,차이유통계학의의(P＜0.05);HRS조AMY(U/L)(5 567±512비5 385 ±572)、LIP (U/L)(1 856.8±149.3비1 924.9±105.4)교ANP조하강,단차이무통계학의의(P＞0.05).HRS조ALT(U/L)(134.8±11.8비156.9±15.8)、AST(U/L)(326.6±20.5비448.5±53.0)급간장적병리분급(17.1비23.1)교ANP조유현저강저,차이유통계학의의(P＜0.05);ANP조간장조직SOD(U/mg)(127.2±11.6비267.4±33.2)활성수평교SO조유명현강저,MDA (nmol/mg)(12.6±3.1비3.9±1.7)수평명현승고,차이유통계학의의(P＜0.05),HRS조간장조직중SOD (U/mg)(177.4±12.5비127.2±11.6)활성교ANP조유현저승고,MDA(nmoL/mg)(9.7±2.3비12.6±3.1)함량현저강저,차이유통계학의의(P＜0.05).ANP조간장조직중p-JNK(121.40±10.70비2.60±0.45),p-p38(63.1±6.9비16.2±1.7),p-ERK(7.10±1.40비0.90±0.04)수평비교우SO조명현승고,차이유통계학의의(P＜0.05),HRS조p-JNK(51.30±9.70비121.40±10.70)급p-p38(16.2±1.7비63.1±7.0)수평비교우ANP조유현저하강,차이유통계학의의(P＜0.05),단p-ERK(6.70±1.30비7.10±1.40)표체차이무통계학의의(P＞0.05).결론 HRS가유유효적강저ANP대서간장양화응격,종이감소ROS대JNK급p38통로적격활,종이대ANP대서간장기도보호작용.
    Objective To investigate the impact of hydrogen-rich saline on mitogen-activated protein kinases (MAPKs) pathway in hepatic reactive oxygen species (ROS) activation in acute necrotizing pancreatiis (ANP) and protective effect of hydrogen-rich saline on hepatic injury of ANP in rat.Methods Ninety male Wistar rats were randomly divided into three groups:sham operation group (SO group),ANP group and hydrogen-rich saline treatment group (HRS group),each group further divided into three (3,12,24 h) subgroup (n =10).ANP model was induced by retrograde infusion of 5％ sodium taurocholate into the biliopancreatic duct.Hydrogen-rich saline was injected through the tail vein (6 ml/kg) and under the skin (20 ml/kg) at 5 minutes after the operation in HRS group.The rats of SO group and ANP group were administered by intravenous (6 ml/kg) and subcutaneous (20 ml/kg) injection with saline.Rats in each group were sacrificed at 3,12 and 24 h after the operation.The levels of serum amylase (AMY),lipase (LIP),alanine transaminase (ALT),aspartate aminotransferase (AST) and histopathological scores or grades of pancreatic and liver tissues were measured.Hepatic malondialdehyde content and superoxide dismutase activity were analyzed.Results The levels of serum AMY (U/L) (5 385 ± 572 vs.1 146±121),LIP (U/L) (1 924.9±105.4vs.86.5±8.9),ALT (U/L) (156.9±15.8 vs.56.1±5.4),AST (U/L) (448.5 ±53.0 vs.124.6 ± 14.7),and histopathological scores of pancreatic tissues (13.79 ± 1.36 vs.0.38 ±0.53) in ANP group increased significantly than SO group (P ＜0.05).serum AMY (U/L) (5 567 ±512 vs.5 385 ±572) and LIP (U/L) (1 856.8 ± 149.3 vs.1 924.9 ± 105.4) in HRS group decreased than ANP group,but no statistical significance (P ＞ 0.05).serum ALT (U/L) (134.8±11.8 vs.156.9±15.8),AST (U/L) (326.6±20.5 vs.448.5±53.0) and hepatic histopathological grades (17.1 vs.23.1) in HRS group decreased significantly than ANP group (P ＜ 0.05).Hepatic superoxide dismutase activity decreased in ANP group than SO group and hepatic malondialdehyde acyivity [(12.6 ± 3.1) vs.(3.9 ± 1.7) nmol/mg] increased in ANP group than SO group (P ＜ 0.05).Hepatic superoxide dismutase activity [(177.4 ± 12.5) vs.(127.2 ± 11.6) U/mg] in HRS group were higher than ANP group and hepatic malondialdehyde acyivity [(9.7 ± 2.3) vs.(12.6 ± 3.1) nmol/mg]lower significantly than ANP group (P ＜ 0.05).Hepatic phosphorylated c-Jun N-terminal kinase [p-JNK (121.40 ± 10.70 vs.2.60 ± 0.45)],p-p38 (63.1 ± 6.9 vs.16.2 ± 1.7),phosphorylated extracellular signal-regulated kinase [p-ERK (7.10 ± 1.40 vs.0.90 ± 0.04)] expression in ANP group increased significantly than SO group (P ＜ 0.05).in HRS group,Hepatic p-JNK (51.30 ± 9.70 vs.121.40 ± 10.70),p-p38 (16.2 ± 1.7 vs.63.1 ± 7.0) expression decreased significantly than in ANP group (P ＜ 0.05),but the p-ERK (6.70 ± 1.30 vs.7.10 ± 1.40) expression was no significance (P ＞ 0.05).Conclusion Hydrogen-rich saline may effectively decrease hepatic oxidative stress in ANP rat and decrease ROS activation of JNK and p38 pathway.By this way,has a protective effect for hepatic injury of ANP rat.
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