ABSTRACT
Morphine, commonly used to relieve the acute or chronic pain, has a high potential for addiction and exerts rewarding effects via a critical role for mesolimbic dopamine system. Studies suggest that addiction-related behavior is highly associated with inflammatory immune response, but the mechanisms are poorly understood. The present study showed that intra-VTA microinjection of TLR4 antagonist LPS-RS prevented the acquisition and maintenance, but not the expression, of morphine-induced CPP in rats. In addition, chronic morphine treatment significantly activated STAT3 on day 6 and 11 in VTA, and bilateral microinjection of STAT3 inhibitor S3I-201 into the VTA suppressed the acquisition and maintenance of morphine-induced CPP in rats. Furthermore, local knockout of STAT3 by injection of the AAV-Cre-GFP into the VTA area of STAT3flox/flox mice also significantly impaired the acquisition of morphine CPP. Importantly, the TLR4 expression is colocalized with p-STAT3-positive cell in VTA, and repeated injection of LPS-RS significantly attenuated the STAT3 activation in VTA induced by chronic morphine treatment. Collectively, these data suggest that TLR4/STAT3 signaling pathway in VTA might play a critical role in the acquisition and maintenance of morphine CPP, and provides new evidence that TLR4/STAT3 signaling pathway might be a potential target for treatment of morphine addiction.
Subject(s)
Conditioning, Classical/drug effects , Morphine Dependence/metabolism , Morphine/pharmacology , STAT3 Transcription Factor/metabolism , Toll-Like Receptor 4/metabolism , Ventral Tegmental Area/drug effects , Ventral Tegmental Area/metabolism , Animals , Male , Morphine Dependence/immunology , Narcotics/pharmacology , Rats , Rats, Sprague-Dawley , Reward , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/immunology , Signal Transduction/drug effects , Toll-Like Receptor 4/antagonists & inhibitors , Toll-Like Receptor 4/immunology , Ventral Tegmental Area/immunologyABSTRACT
OBJECTIVE: To investigate the effect of VEGF (vascular endothelial growth factor) gene therapy and skin flap delay on the survival of rat's abdominal axial skin flap. METHODS: In 48 Wistar rats, the model of a abdominal axial skin flap supplied by right superficial epigastric vessel was created. The rats were divided into six groups. The group was treated with subcutaneous injection of pcDNA4-VEGF165, skin flap delay or VEGF injection combined with skin flap delay. 7 days later, the survival rate of the skin flap was measured; specimens were harvested from the skin flap for histological investigation of the microvessels and for immunohistochemical staining to observe the expression of VEGF. RESULTS: Every treated group was significantly higher than blank group in the average survival rate of the skin flap and group V (gene injection when delayed) has the highest one. The average number of the microvessels in group II, III, V, VI was significantly higher than group IV and blank group. Group IV > group V, VI > group II, III > blank group in lumen diameter of the microvessels. Immunohistochemical staining documented more deposition of VEGF DNA in group II, III, V, VI than group IV and blank group. CONCLUSIONS: Both administration of pcDNA4-VEGF165 and skin flap delay can improve the survival of rat's abdominal axial skin flap, but the mechanisms of the effect were different. The combination of the two ways has stronger effect.
Subject(s)
Abdominal Wall/surgery , Genetic Therapy , Graft Survival , Vascular Endothelial Growth Factor A/genetics , Animals , Disease Models, Animal , Genetic Vectors , Male , Rats , Rats, Wistar , Surgical FlapsABSTRACT
OBJECTIVE: To study some related factors of effect on gluteus muscle contraction and provide the therapeutic basis. METHODS: The curative effect was assessed in 154 patients who were classified by age, patient's condition, orthopedic degree in operation and rehabilitation with an average follow-up period of 25 months(ranging from 5 to 36 months). RESULTS: The excellent rate of 18-24 years old (25/30) was lower than that of 5-17 years old(120/124) (P < 0.05); the excellent rate of slight patients was higher (107/109) than that of serious patients (38/45) (P < 0.01); the excellent rate from higher orthopedic degree was higher (111/113) than that from lower orthopedic degree (34/41) (P < 0.01); and the excellent rate of rehabilitation was much higher (107/110) than that of general treatment (38/44) (P < 0.05). CONCLUSION: Age, patient's condition, orthopedic degree in operation and rehabilitation are important factors to affect the curative effect on gluteu muscle contraction.