Department of General Surgery, Xiangya third hospital, Central South University, Changsha 410013, China.
Inflamm Res. 2012 Nov;61(11):1203-9. doi: 10.1007/s00011-012-0517-8. Epub 2012 Jul 18.
Pancreatic encephalopathy (PE) is a severe complication and significant cause of death in patients with severe acute pancreatitis (SAP). We have reported previously that low-molecular-weight heparin (LMWH) treatment could reduce incidence of PE in SAP patients. Our objective here was to investigate the protective effect of LMWH and its mechanism on PE in SAP rats.
SD rats were randomly divided into three groups: (1) Sham-operation (S) group, (2) SAP group, and (3) LMWH treatment (LMWH) group. LMWH was administrated 4 h after the SAP model conducted. The levels of serum amylase, myelin basic protein (MBP), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), brain water content, occurrence of apoptosis, and pathological changes of pancreas and brain were measured at 1 day after models were set up in the SAP and S groups, and 1 day after LMWH treatment was administrated in the LMWH group.
(1) The levels of serum amylase, TNF-α, and IL-6 in the SAP group were increased significantly more than those in the S and LMWH groups (all P < 0.001), as were the levels of serum MBP in the SAP group compared to those in the S and LMWH groups (P < 0.01, <0.05 respectively). However, while the level of serum amylase and IL-6 in the LMWH group were significantly increased compared to those in the S group (P < 0.05, <0.001 respectively), the levels of TNF-α and MBP showed no significant difference between the LMWH and S groups (all P > 0.05). (2) The brain water content in the SAP group was significantly increased compared to the S group and LMWH group (P < 0.01, <0.05 respectively). (3) Neuronal apoptosis, demyelination, and mitochondrial vacuolation in neuronal cells were observed in the SAP group; in contrast, in the LMWH group, significantly lower rates of neuronal apoptosis, demyelination and mitochondrial edema were observed in neuronal cells.
The protective effect of LMWH on PE progression in SAP rats might result from inhibition of inflammatory activation and reduction of the occurrence of neuronal apoptosis.
胰腺脑病（PE）是重症急性胰腺炎（SAP）患者的一种严重并发症和重要死亡原因。我们之前曾报道过，低分子肝素（LMWH）治疗可降低 SAP 患者 PE 的发生率。本研究旨在探讨 LMWH 对 SAP 大鼠 PE 的保护作用及其机制。
SD 大鼠随机分为三组：（1）假手术（S）组，（2）SAP 组，和（3）LMWH 治疗（LMWH）组。SAP 模型建立后 4 h 给予 LMWH 治疗。在 SAP 组和 S 组模型建立后 1 天以及 LMWH 治疗组给予 LMWH 治疗后 1 天，测量血清淀粉酶、髓鞘碱性蛋白（MBP）、肿瘤坏死因子-α（TNF-α）、白细胞介素 6（IL-6）、脑水含量、细胞凋亡发生率以及胰腺和脑组织的病理变化。
（1）SAP 组血清淀粉酶、TNF-α 和 IL-6 水平明显高于 S 组和 LMWH 组（均 P < 0.001），SAP 组血清 MBP 水平亦明显高于 S 组和 LMWH 组（P < 0.01，P < 0.05）。然而，LMWH 组血清淀粉酶和 IL-6 水平明显高于 S 组（P < 0.05，P < 0.001），而 TNF-α 和 MBP 水平两组间无显著差异（均 P > 0.05）。（2）SAP 组脑水含量明显高于 S 组和 LMWH 组（P < 0.01，P < 0.05）。（3）SAP 组神经元细胞出现神经元凋亡、脱髓鞘和线粒体空泡化；相反，LMWH 组神经元细胞的神经元凋亡、脱髓鞘和线粒体水肿发生率明显降低。
LMWH 对 SAP 大鼠 PE 进展的保护作用可能是通过抑制炎症激活和减少神经元凋亡的发生实现的。
