The Study Of The Clinical Observation And The Mechanism Of Infantile Hemangioma Treatment With Propranolol

Part oneTreatment of problematic infantile hemangiomas with propranololObjective:To evaluate the clinical efficiency and safety of propranlol in the treatment of problematic infantile hemangioma.Methods:Oral propranolol was administered to 68 infants with hemangiomas diagnozed by clincal evalution and adjuvant examination at a dose of 1.0～2.0mg per kilogram of body weight per day, divided for two or three times. The patients were revisited once a month. The changes of the tumor size, texture and colour were monitored and recorded at a regular interval. The adverse effects after medication were observed and managed accordingly. The short-term results were evaluated using a 4 Scales system.Results:Among the 68 patients, the follow-up time was 3 to 13 months. The overall response was scaleⅠin 8 patients, scaleⅡin 13 patients, scale HI in 29 patients, and scaleⅣin 13 patients. No serious adverse effects were encountered, but no one was entirely cured.Conclusions1.Oral propranolol is a safe and effective method for the treatment of infantile heamngioma. The short-term results were excellent and the side effects were minimal. It could be the primary drug for problematic infantile hemangioma. The dose and the course were given respectively. Taking or stopping the therapy shoud be gradually.2.The lesion wasn't regress totally after the treatment, the scar or color weaknees maybe occur in the lesion. So the drug must to be used early as soon as the problematic hemangioma is diagnosed,The remained lesions should be removed with other therapies if neccessary. Part twoImpacts of propranolol on vascular endothelial growth factor in HUVEC-12 Cell and the signaling mechanism in the processObjective To study the impacts of propranolol on vascular endothelial growth factor in HUVEC-12 Cell and the signaling mechanism in the process.Methods The HUVEC-12 Cell were cultured and then was intervened with propranolol concentration of 16ug/ml,8ug/ml,4ug/ml,2ug/ml,1ug/ml,0ug/ml (negative control), VEGF in cultural supernatants of the six groups was evaluated using enzyme-linked immunosorbent assay. The best concentration to precipitate the HUVEC proliferation of VEGF was examined with MTT method and a positive system was created. The expression of P-JNK (phosphorylated JNK) and p-P38 (phosphorylation P38) intervened by different concentration of propranolol group were evaluated using western blot.Results1. The cell toxicity in different concentration of propranolol Compare the study group with the control group with MTT method, there is no statistical difference after HUVEC-12 was intervened by different concentration of propranolol in cell toxicity trial.2. The concentrations of VEGF in cultural supernatants of different groups:the concentrations of the VEGF in cultural supernatants of 16ug/ml,8ug/ml,4ug/ml,2ug/ml and 1ug/ml. The concentration reduced significantly compared with the negative control group(P<0.05), and most apparently, in 8ug/ml.3. The proliferation impact of human vascular endothelial cell in different VEGF concentration:In cell proliferation trial, HUVEC-12 cell was intervened by the VEGF concentration of 40ng/ml,20ng/ml, 10ng/ml,5ng/ml,2.5ng/ml for 48 hours. VEGF has effect in promoting HUVEC-12 cells proliferation, which is most significant at the concentration of 20ng/ml(P<0.001), in contrasted with the control group.4. The expression of JNK and P38 in propranolol treatment group: the expression of JNK and P38 first increased and decreased after, along with the increasing of concentration. The strongest expression of JNK was in 1ug/ml, P38 was in 4ug/ml. Both weakened in 16 ug/ml.Conclusion1. Propranolol could inhibit the secretion of VEGF in HUVEC-12 cells, it was most apparent in 8ug/ml.2. Protein kinases JNK and P38 may played an important roles in the process of propranolol affecting the secretion of VEGF, In high concentration, it down-regulated JNK and P38 signal transduction of vascular endothelial cell and demote the proliferation efficiency to precipitate the regression of hemangioma.