急性坏死性胰腺炎早期胰腺组织趋化因子基因的表达及氧化苦参碱的影响

Chemokine gene expression in pancreatic tissue and effects of oxymatrine in early acute necrotizing pancreatitis

目的:探讨细胞因子诱导的中性粒细胞趋化因子(CINC)和单核细胞趋化蛋白(MCP-1/JE)在大鼠急性坏死性胰腺炎(ANP)早期胰腺组织中的表达,观察中药提取物氧化苦参碱(Oxy)对其表达水平的影响以及在ANP中的治疗作用.方法:以牛磺胆酸钠逆行胆胰管注射制备大鼠ANP模型,56只SD大鼠随机分为假手术(SO)组,ANP3h,6h,12h组,Oxy治疗3h,6h,12h组,检测各组血清淀粉酶(Amy),谷丙转氨酶(ALT)和肌酐(Cr)值,观察胰腺组织病理学和胰腺组织中CINC及MCP-1/JE基因表达的改变.结果:比较SO组,CINCmRNA、MCP-1/JEmRNA在ANP各组胰腺组织中表达量显著增加(分别为0.61±0.08,0.76±0.10,0.89±0.12,0.42±0.06,0.65±0.08,0.94±0.12,P<0.01),随诱发ANP时间的进展有不断上调的趋势,且都与胰腺组织病理学改变呈正相关(分别为0.89,0.82,P<0.05),与ANP各组比较,Oxy治疗各组CINCmRNA,MCP-1/JEmRNA表达量有明显下降(0.34±0.05,0.45±0.06,0.51±0.06,0.31±0.04,0.34±0.04,0.36±0.05,P<0.01),血清Amy,ALT和Cr值降低(分别为25.39±1.93μkat,37.66±4.27μkat,96.00±9.19μkat,94.5±58.3nkat/L,283.8±115.5nkat/L,469.7±157.3nkat/L,81.4±17.7μmol/L,89.1±18.7μmol/L,110.7±12.8μmol/L,P<0.05或P<0.01),胰腺组织病理学损害改善(5.95±0.17,6.53±0.19,7.58±0.20,P<0.01).结论:CINC和MCP-1/JE是ANP早期重要的炎症反应递质,Oxy能抑制他们在ANP大鼠胰腺组织中的表达,对ANP有一定的治疗作用.

AIM: To investigate the expression of cytokine-induced neutrophil chemoattractant (CINC) and monocyte chemoattractant protein-1/JE (MCP-1/JE) genes in the pancreas, and to assess the influence of Chinese herb extraction oxymatrine (Oxy) on the expression of CINC and MCP-1/JE genes and the therapeutic effects in early acute necrotizing pancreatitis (ANP). METHODS: ANP was induced by retrograde infusion of 50 g/L sodium taurocholate into the biliary pancreatic duct of rats. Fifty-six rats were randomly divided into three groups:sham operation (SO) group, ANP 3 h, 6 h, 12 h groups, and Oxy 3 h, 6 h, 12 h groups. The activity of serum amylase (Amy), the serum levels of glutamic-pyru-vic transaminase (ALT) and creatinine (Cr) were determined. Pathological changes of the pancreas were observed. The expression of CINC and MCP-1/JE genes in the pancreas was assayed. RESULTS: Compared with that in SO group, the expression of CINC and MCP-1/JE genes in the pancreas in ANP groups were all increased greatly (0.61±0.08, 0.76±0.10, 0.89±0.12, 0.42±0.06, 0.65±0.08, 0.94±0.12, P<0.01). Following the induction of ANP, the expression of CINC and MCP-1/JE genes was both up-regulated, which was significantly correlated with the pathological changes of the pancreas (r= 0.89 and 0.82, respectively, P<0.05). Oxy attenuated the increase of CINC and MCP-1/JE gene expression (0.34±0.05,0.45±0.06,0.51±0.06 vs 0.31±0.04, 0.34±0.04, 0.36±0.05, in ANP 3 h, 6 h, 12 h groups and Oxy 3 h, 6 h, 12 h groups, respectively P<0.01). Serum Amy, ALT and Cr levels were reduced, (Amy:25.39±1.93 μkat, 37.66±4.27 μkat, 96.00±9.19 μkat; ALT:94.5±58.3 nkat/L, 283.8±115.5 nkat/L, 469.7±157.3 nkat/L; Cr: 81.4±17.7 μmol/L, 89.1±18.7 μmol/L, 110.7±12.8 μmol/L, P<0.05 or P<0.01), and the pathological changes of pancreas were ameliorated by Oxy. CONCLUSION: CINC and MCP-1/JE might play important roles in early ANP. The expression of CINC and MCP-1/JE gene in the pancreas can be inhibited by Oxy. Oxy therapy was effective in experimental ANP.