CAJ | 학술논문

目的探讨急性坏死性胰腺炎(ANP)胰腺组织中褪黑激素受体MT1表达及褪黑激素(MT)干预作用.方法 54只SD大鼠随机分为假手术组(SO组)、急性坏死性胰腺炎组(ANP组)、MT干预组(MT组),每组18只.应用胰胆管逆行注射牛磺胆酸钠的方法诱导ANP模型,MT组于诱导模型前30 min腹腔注射MT.术后4 h、8 h和12 h分批处死大鼠(每个时间点6只),以免疫组化和实时定量PCR分别检测胰腺组织中MT1蛋白及MT1 mRNA的表达;检测血清淀粉酶、胰腺组织中丙二醛(MDA)、超氧化物歧化酶(SOD)及TNFα的含量,并行胰腺病理检查.结果 (1)ANP组胰腺病理损伤呈进行性加重,MT组胰腺病理损伤较ANP组明显减轻(P＜0.05).(2)淀粉酶、MDA、TNFα水平在ANP组较S0组明显增高(P＜0.05或P＜0.01),而MT组较相应时间点ANP组显著降低[12 h,(2348.00±278.90)U/L比(3194.83±538.10)U/L,(2.255±0.472)μmol/L比(2.960±0.722)μmol/L,(102.929±29.399)ng/L比(378.544±183.454)ng/L,P＜0.05].SOD水平在ANP组各时点较SO组显著降低(P＜0.01),而MT组较ANP组显著升高[12 h,(11.448±1.594)U/L比(8.427±1.950)U/L,P＜0.05].(3)与SO组相比,MT1蛋白及MT1 mRNA表达在ANP组胰腺组织中明显下降(P＜0.05),且随ANP病变加重表达减弱,而MT组表达较ANP组明显增多.结论 MT干预可提高SOD活力,降低MDA、TNFα水平,故能显著减轻ANP时胰腺病理损伤,MT1在ANP发病机制中可能具有重要作用,MT对ANP中的干预作用可能与上调胰腺组织中MT1的表达有关.
목적 탐토급성배사성이선염(ANP)이선조직중퇴흑격소수체MT1표체급퇴흑격소(MT)간예작용.방법 54지SD대서수궤분위가수술조(SO조)、급성배사성이선염조(ANP조)、MT간예조(MT조),매조18지.응용이담관역행주사우광담산납적방법유도ANP모형,MT조우유도모형전30 min복강주사MT.술후4 h、8 h화12 h분비처사대서(매개시간점6지),이면역조화화실시정량PCR분별검측이선조직중MT1단백급MT1 mRNA적표체;검측혈청정분매、이선조직중병이철(MDA)、초양화물기화매(SOD)급TNFα적함량,병행이선병리검사.결과 (1)ANP조이선병리손상정진행성가중,MT조이선병리손상교ANP조명현감경(P＜0.05).(2)정분매、MDA、TNFα수평재ANP조교S0조명현증고(P＜0.05혹P＜0.01),이MT조교상응시간점ANP조현저강저[12 h,(2348.00±278.90)U/L비(3194.83±538.10)U/L,(2.255±0.472)μmol/L비(2.960±0.722)μmol/L,(102.929±29.399)ng/L비(378.544±183.454)ng/L,P＜0.05].SOD수평재ANP조각시점교SO조현저강저(P＜0.01),이MT조교ANP조현저승고[12 h,(11.448±1.594)U/L비(8.427±1.950)U/L,P＜0.05].(3)여SO조상비,MT1단백급MT1 mRNA표체재ANP조이선조직중명현하강(P＜0.05),차수ANP병변가중표체감약,이MT조표체교ANP조명현증다.결론 MT간예가제고SOD활력,강저MDA、TNFα수평,고능현저감경ANP시이선병리손상,MT1재ANP발병궤제중가능구유중요작용,MT대ANP중적간예작용가능여상조이선조직중MT1적표체유관.
Objective To investigate the expression of melatonin MT1 receptor in rats with acute necrotizing pancreatitis (ANP) and the protective effects of melatonin (MT) pre-intervention for the pancreas. Methods Fifty-four male Sprague-Dawley (SD) rats were randomly divided into three groups:sham-operation group, ANP group and MT-pretreated group. The models of ANP were induced by retrograde injection sodium taurocholate into the bili-pancreatic duct. MT group undergoing intraperitoneal injection 50 mg/kg 30 minutes before the establishment of ANP models. Four, 8 and 12 hours after the onset of operation, the levels of serum amylase and pathological changes of the pancreas were observed. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNFα) in the pancreas were measured. The expression of MT1 protein and MT1 mRNA in pancreas were separately analyzed by immunohistochemistry and real-time PCR. Results (1) Pancreatic pathological damage in ANP groups was progressive exacerbated. It was obviously ameliorated in MT group as compared with ANP group ( P ＜ 0.05 ); (2) Compared with SO group, the levels of serum amylase, MDA and TNFα in the pancreas were significantly increased in ANP group (P ＜0.05 or P ＜0.01 ). They were markedly decreased in MT group as compared with ANP group [ 12 h, (2348.00 ±278.90)U/L vs (3194. 83 ±538.10)U/L,(2.255 ± 0.472 ) μmol/L vs ( 2.960 ± 0.722 ) μ mol/L, ( 102.929 ± 29.399 ) ng/L vs ( 378. 544 ±183.454)ng/L, P ＜ 0.05 ]. The level of SOD was decreased in ANP group compared with SO group (P ＜0.05) and increased in MT group[ 12h, (11.448 ± 1.594)U/L vs (8.427 ± 1.950)U/L, P＜0.05] ;(3)Compared with SO group, the expression of MT1 protein and MT1 mRNA in ANP group were down-regulated as the severity of the disease increased ( P ＜ 0.05 ). They were significantly higher in MT group than ANP group. Conclusions Melatonin pre-intervention is able to increase SOD level and decrease MDA, TNFα levels, thereby reducing pancreatic injury. The MT1 might play an important role in the pathogenesis of ANP. MT might exert protective effects for the pancreas in ANP rats through increase the expression of MT1.