目的 探究血管內(nèi)皮生長因子（VEGF）對重癥急性胰腺炎大鼠微循環(huán)障礙的改善作用。方法 將SD大鼠隨機分成假手術組、模型組、VEGF組和VEGF抗體組。于大鼠上腹部正中切口，長度約2 cm，尋找胰膽管并以動脈夾夾閉其近端和遠端，40 mg/mL?；悄懰徕c（1 mL/kg）經(jīng)胰膽管逆行注射建立重癥急性胰腺炎模型。造模成功后，VEGF組和VEGF抗體組在分別經(jīng)陰莖背iv VEGF（10 μg/kg）和VEGF抗體（10 μg/kg），假手術組、模型組僅注射PBS溶液。記錄24 h內(nèi)每組小鼠的死亡率，剖殺動物時分別取1 cm³相同部位肝、肺、小腸和胰腺組織，測定各組織含水量（干濕比）。取大鼠門靜脈血4 mL，靜置，離心2 min收集血清，應用ELISA檢測試劑盒檢測VEGF、一氧化氮（NO）、內(nèi)皮素（ET）、胰蛋白酶水平。電鏡下觀察肺、胰腺組織微循環(huán)超微結構的改變。結果 與模型組和VEGF抗體組相比，VEGF組死亡率顯著降低，肝、肺、小腸和胰腺組織的干濕比顯著下降（P＜0.05）。VEGF組VEGF水平顯著高于模型組和VEGF抗體組，NO和ET水平較模型組和VEGF抗體組明顯降低（P＜0.05）。透射電鏡下，模型組和VEGF抗體組透射電鏡可見到典型血管內(nèi)皮細胞凋亡、線粒體腫脹、細胞水腫、毛細血管充血、血栓形成、微循環(huán)血管內(nèi)皮完整性破壞或消失及血管外出血、水腫等病理改變，VEGF組上述變化明顯減輕。結論 VEGF能夠有效改善和緩解重癥急性胰腺炎大鼠微循環(huán)功能失調(diào)。

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

陜西省自然科學基礎研究計劃項目(2020JQ-874)