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.

Ligustrazine alleviates acute renal injury in a rat model of acute necrotizing pancreatitis.

AIM: To evaluate the effect of ligustrazine, a traditional Chinese medicine, on renal 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, 12 h subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. T group was infused sodium taurocholate as above, and 0.6% ligustrazine was then administered via the femoral vein. Serum urea nitrogen (BUN) and creatinine (Cr) concentrations were measured for the evaluation of renal function. The effects of ligustrazine on the severity of renal injury were assessed by renal function, TXA(2)/PGI(2) and histopathological changes. Renal blood flow was determined by the radioactive microsphere technique (RMT). RESULTS: Compared with control group, the renal blood flow in P group was decreased significantly. Serious renal and pancreatic damages were found in P group, the BUN and Cr levels were elevated significantly, and the ratio of TXA(2) to PGI(2) was increased at 2, 6 and 12 h. Compared with P group, the blood flow of kidney was elevated significantly at 6 and 12 h after induction of ANP, the renal and pancreatic damages were attenuated, and the BUN and Cr levels were decreased significantly, and the ratio of TXA(2) to PGI(2) was decreased at 6 and 12 h in T group. CONCLUSION: Microcirculatory disorder (MCD) is an important factor for renal injury in ANP. Ligustrazine can ameliorate the condition of MCD and the damage of pancreas and kidney.