Abstract: BACKGROUND: Lower limb venous embolism is prone to cause complications such as venous thrombosis and pulmonary embolism. If not treated in time, patients may die suddenly. Therefore, it is particularly important to explore an effective treatment method.
OBJECTIVE: To investigate the effects of enalapril folate on the activity of vascular endothelial cells as well as angiotensin II and angiotensin-converting enzyme levels in rats with lower extremity venous embolism. 
METHODS: Forty SPF male Sprague-Dawley rats were randomly divided into normal group, model group, rivaroxaban group, and enalapril folic acid group (n=10 per group). In the latter three groups, animal models of lower extremity venous embolism were established using the modified Reyers method. After modeling, the rats were gavaged 30 mg/kg rivaroxaban in the rivaroxaban group, 20 mg/kg enalapril maleate folic acid tablet in the enalapril folic acid group, and the same volume of normal saline in the model and normal groups for 30 days. During administration, Tarlov score was used to evaluate the lower limb motor function of rats. After administration, hematoxylin-eosin staining was used to detect the pathological morphology of vascular tissue. Hladovec and ELISA were used to detect the activity of endothelial cells. The level of angiotensin II was detected by homogeneous competitive radioimmunoassay and the level of angiotensin-converting enzyme was detected by hippuric acid method.
RESULTS AND CONCLUSION: (1) Compared with the normal group, Tarlov score and serum nitric oxide level were significantly decreased in the model group (P < 0.05), while the number of serum circulating endothelial cells, endothelin 1, hepatocyte growth factor, angiotensin-converting enzyme, and angiotensin II in plasma were significantly increased (P < 0.05). (2) Tarlov scores and serum nitric oxide levels were significantly increased in the rivaroxaban and enalapril folic acid groups compared with the model group (P < 0.05), while the number of serum circulating endothelial cells and levels of endothelin 1, hepatocyte growth factor, angiotensin-converting enzyme, and plasma angiotensin II were significantly increased (P < 0.05). Moreover, the above indicators were significantly improved in the enalapril folate group compared with the rivaroxaban group (P < 0.05). (3) In the normal group, the vascular structure was clear and complete and the intima was intact. In the model group, the rats showed loosed vascular wall tissue, thickened edema, and numerous thromboses, indicating serious organization. After treatment with rivaroxaban and enalapril folic acid, the vascular morphology was improved, with basically intact structure of the vascular wall, and vascular endothelial cells were partially regenerated. The enalapril folic acid group showed better outcomes than the rivaroxaban group. (4) To conclude, enalapril folic acid has dramatically therapeutic effects in the rats with lower extremity venous embolism, which can effectively improve the activity of vascular endothelial cells and reduce the levels of angiotensin II and angiotensin-converting enzyme.

Key words: enalapril folate, lower limb venous embolism, vascular endothelial cell activity, angiotensin II, angiotensin-converting enzyme