目的 探究血管内皮生长因子（VEGF）对重症急性胰腺炎大鼠微循环障碍的改善作用。方法 将SD大鼠随机分成假手术组、模型组、VEGF组和VEGF抗体组。于大鼠上腹部正中切口，长度约2 cm，寻找胰胆管并以动脉夹夹闭其近端和远端，40 mg/mL牛磺胆酸钠（1 mL/kg）经胰胆管逆行注射建立重症急性胰腺炎模型。造模成功后，VEGF组和VEGF抗体组在分别经阴茎背iv VEGF（10 μg/kg）和VEGF抗体（10 μg/kg），假手术组、模型组仅注射PBS溶液。记录24 h内每组小鼠的死亡率，剖杀动物时分别取1 cm³相同部位肝、肺、小肠和胰腺组织，测定各组织含水量（干湿比）。取大鼠门静脉血4 mL，静置，离心2 min收集血清，应用ELISA检测试剂盒检测VEGF、一氧化氮（NO）、内皮素（ET）、胰蛋白酶水平。电镜下观察肺、胰腺组织微循环超微结构的改变。结果 与模型组和VEGF抗体组相比，VEGF组死亡率显著降低，肝、肺、小肠和胰腺组织的干湿比显著下降（P＜0.05）。VEGF组VEGF水平显著高于模型组和VEGF抗体组，NO和ET水平较模型组和VEGF抗体组明显降低（P＜0.05）。透射电镜下，模型组和VEGF抗体组透射电镜可见到典型血管内皮细胞凋亡、线粒体肿胀、细胞水肿、毛细血管充血、血栓形成、微循环血管内皮完整性破坏或消失及血管外出血、水肿等病理改变，VEGF组上述变化明显减轻。结论 VEGF能够有效改善和缓解重症急性胰腺炎大鼠微循环功能失调。

Objective Effect of vascular endothelial growth factor (VEGF) on microcirculation disturbance in severe acute pancreatic rats. Methods A total of 120 SD rats were randomly divided into sham group, severe acute pancreatitis model group, vascular endothelial growth factor (VEGF) group, and VEGF antibody group. A median incision was made in the upper abdomen of rats, about 2 cm in length, to find the pancreaticobile duct and clamp its proximal and distal ends with an arterial clip. The model of severe acute pancreatitis was established by retrograde injection of 40 mg/mL sodium taurocholate (1 mL/kg) into the pancreatobiliary duct. After successful modeling, VEGF (10 μg/kg) and VEGF antibody (10 μg/kg) were injected through dorsal penile vein in VEGF group and anti-VEGF group, respectively. PBS solution was only injected into sham operation group and model group. The mortality rate of each group was recorded over a 24 h period. 1 cm³ liver, lung, small intestine, and pancreas tissues were taken from the same parts of the animals at necropsy, and water content (dry/wet ratio) of each tissue was determined. 4 mL of portal venous blood was collected from rats, stood and centrifuged for 2 min to collect serum. The levels of VEGF, NO, ET, and trypsin were detected by ELISA kit. The ultrastructural changes of microcirculation in lung and pancreas were observed under electron microscope. Results Compared with the model group and VEGF antibody group, the mortality of VEGF group was significantly decreased, and the dry/wet weight ratio of liver, lung, small intestine, and pancreas was significantly decreased (P < 0.05). Levels of VEGF in VEGF group were significantly higher than those in model group and VEGF antibody group, and the levels of NO and ET were significantly lower than those in model group and VEGF antibody group (P < 0.05). Under transmission electron microscope, typical pathological changes such as apoptosis of vascular endothelial cells, mitochondrial swelling, cell edema, capillary congestion, thrombosis, destruction or disappearance of microcirculation vascular endothelial integrity, extravascular bleeding and edema were observed in the model group and VEGF antibody group, and the above changes were significantly reduced in the VEGF group. Conclusion VEGF can effectively improve and alleviate microcirculation dysfunction in rats with severe acute pancreatitis, which is an important breakthrough in the treatment of severe acute pancreatitis.

R965

陕西省自然科学基础研究计划项目(2020JQ-874)