目的 观察评价犬尿喹啉酸预处理对急性坏死性胰腺炎的保护作用。方法 将SD大鼠随机分为对照组、模型组、犬尿喹啉酸（75、150、300 mg/kg）组、乌司他丁组。采用苏木精–伊红（HE）染色检测胰腺病理结构；检测胰腺组织湿/干质量比、血清淀粉酶和髓过氧化物酶（MPO）活性以及白细胞介素（IL）-1β含量；Western blotting检测胰腺组织热休克蛋白72（HSP72）蛋白表达；体内正交偏振光谱成像技术检测胰腺微循环血流动力学。体外分离胰腺腺泡细胞，随机分为对照组、模型组、犬尿喹啉酸组，ELISA法检测IL-1β含量。分离各组大鼠血清中性粒细胞并利用试剂盒检测H₂O₂含量。结果 与模型组比较，犬尿喹啉酸300 mg/kg组和乌司他丁组大鼠胰腺组织水肿程度减轻，炎性细胞浸润减少，坏死胰腺明显减少，水肿评分、组织含水量、白细胞浸润评分、MPO和血清淀粉酶活性、IL-1β含量表达降低，浆膜红细胞速率、HSP72表达及pH和HCO₃^-水平升高（P＜0.05）。与模型组比较，犬尿喹啉酸组中性粒细胞在犬尿喹啉酸处理70 min后H₂O₂产生显著降低（P＜0.05）。结论 犬尿喹啉酸对L-精氨酸诱导的急性坏死性胰腺炎大鼠炎症和血流动力学损伤具有保护作用，其机制可能与上调HSP72蛋白表达有关。

Objective To observe and evaluate the protective effect of kynurenic acid pretreatment on acute necrotizing pancreatitis. Methods SD rats were randomly divided into the control group, the model group, the kynurenic acid (75, 150, 300 mg/kg) groups, and the ulinastatin group. The pathological structure of the pancreas was detected by hematoxylin-eosin (HE) staining. Detect the wet/dry mass ratio of pancreatic tissue, the activities of serum amylase and MPO, and the content of IL-1β. Western blotting was used to detect the expression of HSP72 protein in pancreatic tissue. In vivo orthogonal polarization spectroscopy imaging technology was used to detect the hemodynamics of pancreatic microcirculation. Pancreatic acinar cells were isolated in vitro and randomly divided into the control group, the model group and kynurenic acid group. The content of IL-1β was detected by ELISA. Serum neutrophils of rats in each group were isolated and the content of H₂O₂ was detected using the kit. Results Compared with the model group, the degree of pancreatic tissue edema in the kynurenic acid 300 mg/kg group and the ulinastatin group was alleviated, the infiltration of inflammatory cells was reduced, the necrotic pancreas was significantly decreased, and the expressions of edema score, tissue water content, white blood cell infiltration score, MPO and serum amylase activity, and IL-1β content were decreased. The serous red blood cell rate, HSP72 expression, pH and HCO3^- levels increased (P < 0.05). Compared with the model group, the production of H₂O₂ by neutrophils in the kynurenic acid group was significantly reduced after 70 min of kynurenic acid treatment (P < 0.05). Conclusion Kynurenic acid acid has a protective effect on inflammation and hemodynamic injury in rats with L-arginine-induced acute necrotizing pancreatitis, and the mechanism may be related to the upregulation of HSP72 protein expression.

R975

陕西省重点研发计划项目（2024SF-YBXM-525）