Pge1 Inducing Angiogenesis Clinical And Experimental Research

Background&Obj ectiveAs the rising of living standard and the aging of the social development, the lower limb artery ischemic diseases are increasing obviously. The mainly clinical feature includes physical pain, skin temperature lower and ulcer formation. For the disease mostly involving the tiny artery and peripheral circulation, both surgical and intracavitary treatment are little effect. The medications are the foundational methods, PGE1 is the commonly used medicine.PGE1 can expand peripheral vascular, inhibit platelet aggregation and improve the function of endothelial cells, can increase local blood flow, improve microcirculation and increase the oxygen for local organization.In the clinical application, we found that some patients who used PGE1, found the symptoms have been improved, and in the period of stopping the drugs, clinical features, such as the paining and skin temperature rising higher, did not appear aggravating, so we consider whether PGE1 acts the role of angiogenesis? Are the new blood vessels improving the blood supply of the local tissue? If it is, what's the mechanism of angiogenesis? The clinical and experimental researches are going to reveal the angiogenesis and the mechanism.MethodsClinical sectionThis group of patients with 15 cases, male 9 cases, female 6; The low limb artery occlusion is wide, and peripheral circulation block is serious; 10 patients appeared resting pain, the limp distances were 20-150 m,6 cases have the local ulceration. All of the patients were given PGE110 ug by intravenous injection, two times per day, and two weeks for one period of treatment. Observed and recorded the pain, skin temperature change and ulcer healing, limp distance and percutaneous oxygen partial pressure (TcpO2), with color dopplar ultrasound, CTA/MRA to test the blood supply to the ischemia site.Experiment sectionThe experiment used the human umbilical vein endothelial cells(HUVECs), HUVECs were recovered, culturing and subculturing, took 3-6 generations passage cell, added cell supernatant, configured to 1 x105/ml of cell suspension liquid; added PGE1 and continue to cultivate. Determined contention of vascular endothelial growth factor (VEGF), HUVECs proliferation, transfer, and compared with control groups; And setting angiogenesis blockers (Beacizumab) group, to observe the influence of Bevacizumab for VEGF), HUVECs proliferation, the migration and pipe formed; P38.and ERK phosphorylation signaling pathways widely participate in mitosis, and playing an important role in promoting endothelial cell proliferation, transfer and pipe formed, we guess PGE1 also may be through the ERK and P38 phosphorylation to in promote angiogenesis. So put PGE1, P098059 (ERK phosphorylation blockers), P203580 (P38 phosphorylation blockers) into HUVECs to see the growing of the cell such as proliferation, migration and pipe formed.ResultClinical sectionPGE1 had been used two weeks, resting pain were reduced significantly,8 cases who couldn't sleep in night before treatment can be quiet sleep. The limp distance was increased, the number were from 80 to 270 meters, an average of 80m; 6 cases of the local ulcer area were decreased, two patients'ulcer were healing; TcpO2 were significantly increased. Compared with 2 weeks and 4 weeks, the paining, the limp distance and TcpO2were no changed; Compared with the beginning, the ultrasound indicated that the flow signals of ischemic tissues were colourful in 2 weeks and 4 weeks. And the capillary vessels were richer according to CTA images.Experimental sectionPGE1 induce HUVECs to secrete VEGF, and induce HUVECs Proliferation, migration and pipe formed.Angiogenesis blockers-bevacizumab could block the pathway of PGE1 induction of VEGF and decreased the proliferation, migration and pipe formed of HUVECs.PGE1 promoted HUVECs proliferation and migration and pipe formed by the pathway with ERK and P38 phosphorylation, ERK and P38 phosphorylation blockers-P098059 and P203580 can block ERK and P38 phosphorylation, make HUVECs proliferation, migration and pipe formed less significantly.Conclusions:PGE1 can promote ischemia parts angiogenesis.PGE1 can induce HUVECs to secret VEGF and promote HUVECs proliferation and migration and pipe formed.The mechanism of angiogenesis is by the pathway of ERK and P38 phosphorylation.