急诊预测大鼠重症急性胰腺炎心肌损害严重程度及褪黑素干预保护作用

Prediction of severity of myocardial damage in acute pancreatitis of rats and protective effect of melatonin intervention

目的探讨褪黑素受体1（MR1）、缺血修饰白蛋白（IMA）、心型脂肪酸结合蛋白（FABP）对大鼠重症急性胰腺炎（SAP）心肌损害的急诊预测价值，及褪黑素（MT）的干预保护作用。方法72只SD大鼠采用完全随机化的方法分为假手术组（SO组）、重症急性胰腺炎组（SAP组）、MT干预组（MT组），每组24只。应用胰胆管逆行注射牛磺胆酸钠的方法诱导SAP模型，MT组于诱导模型前30min腹腔注射MT。术后1、4和8h分批处死大鼠（每个时间点8只），免疫组化和实时定量PCR分别检测心脏组织中MR1蛋白及MR1mRNA的表达；检测血清IMA及FABP、肌钙蛋白1（cTnI）、肌酸激酶同工酶（CK—MB）的含量，并行胰腺、心脏组织病理检查。结果（1）SAP组胰腺及心肌病理损伤呈进行性加重，MT组胰腺、心肌病理损伤较SAP组明显减轻（Jp〈001）。（2）IMA、FABP水平在SAP组较SO组均明显增高（P〈0．01），而MT组较相应时间点SAP组均显著降低（P〈0．01）。（3）免疫组化镜下观察，心肌细胞中存在MR1阳性表达，主要分布于胞浆和胞核。与SO组相比，MR1蛋白及MR1mRNA表达在SAP组心脏组织中明显下降（P〈0．01）．且随SAP病变加重表达减弱，而MT组表达较SAP组明显增多。结论IMA、FABP在大鼠SAP中随病情的加重而逐渐升高，MR1随病情发展而表达减少，3者在SAP发生后早期既有变化，对急诊预测SAP心肌损害具有重要意义；经MT干预后，IMA、FABP表达量下降，MR1增加，提示MT对SAP心肌损害有保护作用。

Objective To investigate the emergency predictive value of melatonin receptor1（ MR1 ）, Ischemia modified albumin （IMA）, heart-type fatty acid binding protein （FABP）for the damage of myocardium in severe acute pancreatitis （SAP） of rats and the protective effect of melatonin intervention. Methods Seventy-two male Sprague-Dawley （SD） rats were randomly divided into three groups： sham-operation（ SO ）group, SAP group and MT-pretreated group. The rat SAP model was induced by retrograde injection of sodium taurocholate into bill-pancreatic duct, MT group received intraperitoneal injection of 50 mg/kg 30min before the establishment of SAP. Eight rats in each group were sacrificed at 1, 4 and 8h after the onset of operation respectively, and the serum and tissue samples were taken. The expression of MR1 protein and MR1 mRNA in heart were detected by immunohistochemistry and real-time PCR respectively. The serum levels of IMA, FABP, troponin I （cTnl）, creatine kinase （CK-MB） were measured, and pathological changes of the pancreas and heart were observed. Results The pathological damage of pancreas and heart in SAP groups was progressively exacerbated. It was significantly ameliorated in MT group as compared with SAP group （P〈0.01）. Compared with SO group, the levels of serum IMA, FABP were significantly increased in SAP group （P〈0.01）. They were markedly decreased in MT group as compared with SAP grou（P〈0.01 ）. Immunohlstochemistry revealed that MR1 was expressed in myocardial cells, mainly in the cytoplasm and nucleus. Compared with SO group, the expression of MR1 protein and MR1 mRNA in SAP group were down-regulated as the severity of the disease increased. They were significantly higher in MT group than SAP group. Conclusion IMA, FABP and MR1 expression might be used for emergency prediction of myocardial damage in SAP. MT intervention can protect myocardial damage in SAP of rats.