Ligustrazine alleviates gastric mucosal injury in a rat model of acute necrotizing pancreatitis.
BACKGROUND
Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP.


METHODS
Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group C); ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1beta (IL-1beta) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils.


RESULTS
Blood flow in group P was significantly lower than that in group C (P<0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P<0.01). The level of serum IL-1beta in group P increased more significantly than that in group C (P<0.01). Blood flow of the stomach in group T was significantly higher than that in group P after 2 hours (P<0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P<0.01). Although serum IL-1beta level of group T was higher than of group C (P<0.01), it was lower than that of group P (P<0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P<0.01), and between gastric blood flow and pathological score (r=-0.917, P<0.05).


CONCLUSIONS
Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.
Dang
Sheng-Chun
SC
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Zhang
Jian-Xin
JX
Qu
Jian-Guo
JG
Wang
Xue-Qing
XQ
Fan
Xin
X
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D030004:Ligusticum; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010179:Pancreas / Q000098:blood supply; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy* / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D002121:Calcium Channel Blockers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D011719:Pyrazines; D009195:Peroxidase; C017953:tetramethylpyrazine