Ligustrazine alleviates acute lung injury in a rat model of acute necrotizing pancreatitis.
BACKGROUND
Acute necrotizing pancreatitis leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant lung injury. The aim of this study was to evaluate the effect of ligustrazine, extracted from Ligusticum wallichii a traditional Chinese medicine, on lung injury in a rat model of acute necrotizing pancreatitis (ANP).


METHODS
A total of 192 rats were randomly divided into three groups: control (C group); ANP without treatment (P group); and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6 and 12 hours subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. For the T group, sodium taurocholate was infused as above, then 0.6% ligustrazine was administered via the femoral vein. The effects of ligustrazine on the severity of lung injury were assessed by lung wet/dry weight ratio, myeloperoxidase (MPO) activity and histopathological changes. Pulmonary blood flow was determined by the radioactive microsphere technique (RMT).


RESULTS
The blood flow in the P group was significantly lower than that of the C group, while the blood flow in the T group was significantly higher than that of the P group but showed no significant difference from the C group. Compared with C group, the lung wet/dry ratios in both the P and T groups were significantly increased, but there was no significant difference between them. The MPO activity in the P group was greatly increased over that of the C group. In the T group, although the MPO activity was also higher than in the C group, it much less increased than in the P group. Moreover, the difference between P and T groups was significant after 0.5 to 12 hours. After induction of the ANP model, the pancreas showed mild edema and congestion; the longer the time, the more severe this became. The pulmonary pathological changes were aggravated significantly in the P group. Histopathological scores were higher in the P group than in the C group throughout the experimental course. Histopathological scores in the T group were lower than those in the P group at 6 and 12 hours.


CONCLUSIONS
Microcirculatory disorder is an important factor of lung injury in ANP. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the lung.
Zhang
Jian-Xin
JX
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China. zhangjx@ujs.edu.cn
Dang
Sheng-Chun
SC
D000818:Animals; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D030004:Ligusticum; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications*; D009195:Peroxidase / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
D005343:Fibrinolytic Agents; D010936:Plant Extracts; D011719:Pyrazines; D009195:Peroxidase; C017953:tetramethylpyrazine