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目的探讨低分子量肝素(LMWH)对重症急性胰腺炎(SAP)肾损伤的治疗作用。方法SD大鼠随机分为3组假手术对照组(S组);SAP组;LMWH治疗组(LT组)制成SAP模型后4h给予LMWH治疗。检测SAP组术后24h,LMWH治疗后24h及对照组关腹后24h的血清淀粉酶、肌酐(Cr)、TNF-a水平,肾组织形态学变化和P65基因及P65蛋白的表达。结果SAP组血清淀粉酶、Cr、TNF-a水平显著高于S组和LT组(均P<0.001),LT组血清淀粉酶、Cr水平显著高于S组(P<0.05,P<0.001),但血清TNF-a水平两者无显著差异(P>0.05)。SAP组肾组织P65mRNA及P65蛋白的表达显著高于S组和LT组(均P<0.05)。SAP组肾小管上皮细胞坏死脱落,肾小管水肿、扩张;LT组肾小管水肿和扩张程度较SAP组明显减轻,未见肾小管上皮细胞坏死。结论LMWH通过抑制肾组织NF-κB的活性,下调炎症介质的表达,同时可减少胰酶的释放,从而减轻SAP大鼠肾的损伤。
Objective To investigate the therapeutic effect of low molecular weight heparin (LMWH) on renal injury in severe acute pancreatitis (SAP). Methods SD rats were randomly divided into three groups sham operation control group (S group); SAP group; LMWH treatment group (LT group) made SAP model 4h after LMWH treatment. The levels of serum amylase, creatinine (Cr) and TNF-a, the morphological changes of renal tissue and the expression of P65 gene and P65 protein in serum of 24 h after HSWH treatment and 24 h after LMWH treatment were detected in SAP group. Results Serum amylase, Cr and TNF-a levels in SAP group were significantly higher than those in S group and LT group (all P <0.001). Serum amylase and Cr levels in LT group were significantly higher than those in S group (P <0.05, P <0.001) , But the level of serum TNF-a had no significant difference (P> 0.05). The expression of P65 mRNA and P65 protein in SAP group was significantly higher than that in S group and LT group (all P <0.05). The tubular epithelial cells in SAP group died of necrosis and edema and dilatation of renal tubule. The degree of edema and expansion of tubular in LT group were significantly reduced compared with SAP group. No necrosis of renal tubular epithelial cells was observed. Conclusion LMWH can reduce the renal injury of SAP rats by inhibiting the activity of NF-κB in renal tissue and down-regulating the expression of inflammatory mediators.