The expression of melatonin MT1 receptor in acute necrotizing pancreatitis rats and the protective effects of melatonin / 中华内科杂志

ABSTRACT

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 groupssham-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.