Protective effect of low-molecular-weight heparin on pancreatic encephalopathy in severe acute pancreatic rats.
OBJECTIVE
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.


METHODS
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.


RESULTS
(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.


CONCLUSIONS
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.
Department of General Surgery, Xiangya third hospital, Central South University, Changsha 410013, China.
Fu
F
Qiu
Xin-sheng
XS
Lu
Yu-kun
YK
Huang
D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D046529:Microscopy, Electron, Transmission; D004676:Myelin Basic Protein / Q000097:blood; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010195:Pancreatitis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014867:Water / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D006495:Heparin, Low-Molecular-Weight; D015850:Interleukin-6; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D000681:Amylases