低分子量肝素治疗重症急性胰腺炎大鼠胰性脑病的研究

Low molecular weight heparin therapy for pancreatic encephalopathy in severe acute pancreatitis in rats

目的探讨低分子量肝素(low molecular weight heparin,LMWH)对重症急性胰腺炎(severeacute pancreatitis,SAP)合并胰性脑病的治疗作用。方法SD大鼠随机分为3组:(1)假手术对照组(S组);(2)SAP组;(3)LMWH治疗组(LT组):SAP制模后4 h给予LMWH治疗。检测SAP组和S组制模术后24 h,LMWH治疗后24 h的血清淀粉酶,血清髓鞘碱性蛋白(MBP),IL-6,TNF-α,脑组织含水量,胰腺和脑组织形态学变化。结果(1)SAP组血清淀粉酶,TNF-α,IL-6水平显著高于S组和LT组(均P<0.001),SAP组MBP水平显著高于S组和LT组(P<0.01,P<0.05);LT组血清淀粉酶和IL-6水平显著高于S组(P<0.05,P<0.001),但TNF-α和MBP在LT组及S组间差异无统计学意义(P>0.05)。(2)SAP组的脑组织含水量显著高于S组和LT组(P<0.01,P<0.05)。(3)SAP组胰腺组织大片坏死、出血;LT组胰腺组织坏死、出血程度均较SAP组明显减轻。(4)SAP组的脑组织出现明显神经元细胞凋亡,线粒体空泡变性及有髓神经脱髓鞘改变;LT组的有髓神经脱髓鞘和线粒体水肿较SAP组明显减轻,未见神经元细胞凋亡。结论LMWH可减少胰酶的释放,抑制脑神经元细胞凋亡,同时下调炎症介质的产生,从而减少胰性脑病的发生。

Objective To investigate low molecular weight heparin（LMWH） therapy for pancreatic encephalopathy in severe acute pancreatitis（SAP）.Methods SD rats were randomly divided into 3 groups：（1） Sham operation（S） group,（2） SAP group and（3） LMWH treatment（LT） group：LMWH was administrated at 4 hours after construction of SAP model.The levels of serum amylase,myelin basic protein（MBP）,tumor necrosis factor alpha（TNF-α）,interleukin 6（IL-6）,brain water contents and pathological changes of pancreas and brain were measured at 24 h after models were set up in SAP and in S group,and 24 h after LMWH was administrated in LT group.Results（1） The levels of serum amylase,TNF-α,IL-6 in SAP group were significantly higher than those in S group and LT group（all P 0.001）;the levels of serum MBP in SAP group were significantly higher than those in S group and LT group（P 0.01,0.05 respectively）,and the level of serum amylase and IL-6 in LT group were significantly higher than those in S group（P 0.05,0.001 respectively）;but the levels of TNF-α and MBP showed no significant difference between LT group and S group（all P 0.05）.（2） The brain water content in SAP group was significantly higher than that in S group and LT group（P 0.01,0.05 respectively）.（3） Patch necrosis of acinar cells and massive hemorrhagic changes of pancreas could be observed in SAP group,but the necrosis of acinar cells and hemorrhagic changes in LT group were markedly less severe than those in SAP group.（4） In encephalon tissue of SAP group,demyelination,neuronal apoptosis,and mitochondrial vacuolation in neuronal cells were observed;but in LT group,there were significantly less demyelination and mitochondrial edema of neuronal cells than those in SAP group,and neuronal apoptosis was not found in LT group.Conclusions LMWH treatment can significantly reduce the release of pancreatic enzymes,reduce neuronal apoptosis and inhibit the production of inflammatory mediators,and thus reduce the occurrence of pancreatic encephalopathy in SAP.