ABSTRACT
Objective The activation of P2X7 receptor in ventrolateral periaqueductal gray (vlPAG) is involved in the formation and maintenance of bone cancer pain (BCP). This study will establish a rat model of BCP and observe the effect of the activation of P2X7 receptor in vlPAG on D-serine level through brain microdialysis combined with ELISA. Methods Forty-two female SD rats were divided into four groups by random number table: normal control group (n=12), sham group (n=12), BCP group (n=12) and P2X7 receptor antagonist group (n= 6). The model of metastatic BCP in the tibias of the rats was established in the BCP group, and 20μL of RPMI-1640 medium cell suspension containing SHZ-88 breast cancer cells was injected (1×107 cancer cells/0.5 mL). The sham group was injected with treated cancer cells of the same volume (SHZ-88 breast cancer cells were kept in boiling water at 90 ℃ for 20 min), and the rest of the operation was the same as the BCP group. The normal control group received no treatment. The P2X7 receptor antagonist group was treated the same as the BCP group, except that the P2X7 receptor-specific antagonist A-438079 was added to the perfusion solution. The thermal pain threshold and mechanical pain threshold were detected at the same time in the normal control group, the sham group and the BCP group. The positive expression of P2X7 receptor in vlPAG of rats was detected by immunohistochemistry in each group in 21 days. The changes of D-serine in vlPAG dialysate were detected by ELISA in each group. Results The mechanical pain threshold and thermal pain threshold of the rats in BCP group on Day 5, 7, 10, 14, 18 and 21 were lower than those of the normal control group and sham group (P<0.01). The positive expression of P2X7 was scattered in vlPAG in normal control group and sham group. The number of P2X7 receptor positive cells in the BCP group was significantly higher than that in the control group and sham group (P<0.01). The content of D-serine in vlPAG of the rats in BCP group [(220.28±63.38)ng/mL] was significantly higher than that in the control group [(148.09±46.89)ng/mL] and the sham group [(147.32±51.44)ng/mL] (P<0.05). The content of D-serine in vlPAG [(134.20±41.77)ng/mL] in P2X7 receptor antagonist group was significantly lower than that in BCP group (P<0.05). Conclusion The activation of the P2X7 receptor in ventrolateral periaqueductal gray promotes D-serine release and participates in the mechanisms of BCP in rats .
ABSTRACT
Traumatic brain injury(TBI) can lead to high mortality and disability in children,and can cause great difficulties in treatment worldwide.It is important to prevent and reduce the secondary brain injuries.Therefore,monitoring the brain function,especially the balance of cerebral oxygen metabolism seems to play a very extraordinary role.The mortality and the neurologic sequelae can be improved as long as we detect the cerebral hypoperfusion at the early stage and give timely interventions.Now,the popular monitoring methods include jugular bulb oxygen saturation,regional cerebral oxygen saturation by near infrared spectroscopy,brain tissue oxygen pressure,and cerebral microdialysis.This review aims to summarize the clinical practice of the cerebral oxygen metabolism monitoring methods in TBI children by reviewing the latest research literatures at home and abroad and to provide reference for clinicians to ameliorate the prognosis.
ABSTRACT
To establish a method for detecting micro-dialysis recovery of paeonol, eugenol and piperine in Huoxue Zhitong patch, in order to provide the basis for further percutaneous pharmacokinetics studies. The concentrations of paeonol, eugenol and piperine in dialysates were determined by HPLC, and probe deliveries were calculated respectively. The effects of concentration and calibration approaches on the micro-dialysis probe deliveries of the three components were investigated, and their probe absorbability, in vitro and in vivo probe stability and repeatability were also studied.The results indicated that little paeonol, eugenol and piperine were observed in probes with 30% alcohol as the perfusate, and could be cleaned from probe in a short time. And the in vivo and in vitro probe deliveries of three components were stable within 8 h, drug-containing solution and blank perfusate were alternatively used for three times, and the in vivo and in vitro probe deliveries of three components were basically unchanged. The in vitro recoveries of paeonol, eugenol and piperine with a range of concentration were respectively (45.7±4.66)%, (27.82±2.95)%, (41.3±3.96)%, which indicated no concentration independent. Under the same conditions, the similar delivery was observed by dialysis, retrodialysis and no-net flux. Therefore, the concentrations of analyses of the collected fraction could be calibrated by in vitro or in vivo recoveries. Meanwhile, this also proved that the micro-dialysis method built by this study is applicable to the study on percutaneous pharmacokinetics of Huoxue Zhitong patch.