It has been established that the dipeptidyl peptidase-4 (DPP-4) inhibitor Diprotin A TFA can reduce vascular endothelial (VE)-cadherin disruption by inhibiting the increase in cleaved β-catenin in response to hypoxia, thereby protecting the vascular barrier of human umbilical vein endothelial cells. In this study, we sought to investigate the possible effect of Diprotin A TFA on the VE barrier after cerebral ischemic stroke in mice.

C57BL/6J mice were divided into five groups, namely, (1) sham, (2) stroke, (3) stroke + dimethyl sulfoxide (DMSO), (4) stroke + Diprotin A TFA, and (5) stroke + Diprotin A TFA + XAV-939. First, the cerebral ischemia model was established by photothrombotic ischemia, followed by intraperitoneal injection with Diprotin A TFA and XAV-939 at doses of 70 μg/kg and 40 mg/kg 30 min once in the morning and once in the evening for 3 days. Immunofluorescence staining and Western blot methods were used to analyze the expression of vascular and blood-brain barrier (BBB)-associated molecular markers in the peri-infarct area.

Compared with the vehicle control group, we found that mice injected with Diprotin A TFA exhibited reduced cerebral infarction volume, increased vascular area and length around the brain injury, increased pericyte and basement membrane coverage, upregulated expression of BBB tight junction proteins, and improved their BBB permeability, whereas the group injected with both drug and inhibitor exhibited significantly aggravated vascular injury and BBB permeability.

Diprotin A TFA can reduce VE-cadherin disruption by inhibiting ischemia-hypoxia-induced β-catenin cleavage to protect blood vessels.

已确定二肽基肽酶-4 (DPP-4) 抑制剂 Diprotin A TFA 可通过抑制因缺氧而裂解的 β-catenin 的增加来减少血管内皮 (VE)-钙粘蛋白的破坏，从而保护人体的血管屏障。脐静脉内皮细胞。在这项研究中，我们试图研究 Diprotin A TFA 对小鼠脑缺血性卒中后 VE 屏障的可能影响。

C57BL/6J小鼠分为5组，即（1）假手术组、（2）中风组、（3）中风+二甲基亚砜（DMSO）、（4）中风+双蛋白A TFA和（5）中风+双蛋白A TFA + XAV-939。首先通过光栓缺血建立脑缺血模型，然后分别以70 μg/kg和40 mg/kg剂量的Diprotin A TFA和XAV-939腹腔注射30分钟，早上一次，晚上一次，连续3天. 采用免疫荧光染色和蛋白质印迹法分析梗死周围区域血管和血脑屏障（BBB）相关分子标志物的表达。

与载体对照组相比，我们发现注射Diprotin A TFA的小鼠脑梗死体积减少，脑损伤周围血管面积和长度增加，周细胞和基底膜覆盖率增加，BBB紧密连接蛋白表达上调，并改善了脑损伤周围的血管面积和长度。 BBB 通透性，而同时注射药物和抑制剂的组表现出显着加重的血管损伤和 BBB 通透性。

Diprotin A TFA 可以通过抑制缺血缺氧诱导的 β-catenin 裂解来减少 VE-cadherin 破坏，从而保护血管。