The Effect Of4-HPR Combined With Ultrasound Intervention On The Keliod Implanted In Nude Mice Model

Objective:To explore the effect and mechanism of N-4-hydroxyphenyl retinamide (4-HPR) combined with ultrasound treatment on xenografted keliod in nude mice.Methods:Human keloid were inoculated in to BALB/c nude mice, then the keloid-bearing mice were randomly divided into four groups,5mice for each group: Control group,0.3ml normal saline contains0.04%DMSO were injected into the keloid; Ultrasound group, keloid were treated with1.25W/m2ultrasonic therapeutic;4-HPR group,4-HPR (12.5mg/Kg)were injected into the keloid;4-HPR combined with ultrasound group4-HPR(12.5mg/Kg)were injected into the keloid then keloid were treated with ultrasonic therapeutic. Treatment continuous for30days and twice for each week. Observe the growing condition of the keloid and the volume of the keloid was measured. On postoperative30days, Keloid and blood were harvested. To observe the morphological changes and the expressions of Bcl-2and Bax of fibrocyte by inmmunohistochemistry and hematoxylin-eosin staining. The expression of Bcl-2, Bax and p53were measureed by Real Time PCR with keliod. In order to further observe pharmacological toxic effect of4-HPR to the rat, measure the liver and renal function with blood. To observe the pathological changes of heart, liver, spleen and kidney by hematoxylin-eosin staining.Results:4-HPR and ultrasound therapeutic have inhibitory effect to the formation of keloid in mice while4-HPR combind with ultrasound therapeutic has significant inhibitory effect to it. Hematoxylin-eosin staining showed that fibrocyte reduced, nucleus get smaller, cells arranged by the treatment of4-HPR combined with ultrasound therapeutic, Inmmunohistochemistry showed Bcl-2reduced and the express of protin Bax rised in group4-HPR and4-HPR combined with ultrasound group, the result is more significant in4-HPR combined with ultrasound group than4-HPR group (p<0.05). Real Time PCR showed that Bcl-2reduced and the expression of Bax and p53rised in both4-HPR group4-HPR combined with ultrasound group (p<0.05) There is no Histopathological chang in nude rat with keloid, which teated with4-HPR combind with ultrasound therapeutic.Conclusions:1.4-HPR and ultrasound therapeutic have inhibitory effect to the formation of keloid in mice while4-HPR combind with ultrasound therapeutic has significant inhibitory effect to it.2. The inhibition may transform the expression of bcl-2, bax and p53. thus induct into fiber cell apoptosis.3. There is no Histopathological chang in nude rat with keloid, which teated with4-HPR combind with ultrasound therapeutic.