OBJECTIVE: To investigate the effect and the possible influential mechanisms of hyperbaric oxygen (HBO) and 5-fluorouracil (5-FU) on the proliferation and metastasis in human nasopharyngeal carcinoma (NPC) CNE2Z cell line. METHOD: NPC CNE2Z cell line were divided into 4 groups randomly: group A: control group; group B: 5-FU group; group C: HBO group; group D: 5-FU and HBO group. The inhibition effect of proliferation in CNE2Z cells of all groups through 24 h, 48 h and 72 h disposal was detected by MTT reduction assay; Transwell chamber assay was performed to determine the effect of HBO and (or) 5-FU on the metastasis of the CNE2Z cells; The MMP-9, VEGF expression in CNE2Z cells of all groups were detected by SP immunocytochemical stain and observe the expressed image by micro. RESULT: There were statistical difference on the inhibition effect of proliferation in C group and A group after 48 h and 72 h disposal (P<0.01) and between A, B, C group and D group only after 48 h disposal (P<0.05); There were not statistical difference on the effect of metastasis in C group and A group (P>0.05) and between B, C group and D group (P>0.05); Average optical of the MMP-9, VEGF expression were not statistically significant difference in C group and A group (P>0.05) and between C group and D group (P>0.05). CONCLUSION Simple HBO disposal after 48 h and 72 h could inhibit the proliferation potential of NPC CNE2Z cell line, but the combination of HBO and 5-FU only after 48 h disposal could all the more inhibit the proliferation potential. Simple HBO disposal couldn't decrease the MMP-9 and VEGF high-expression and inhibit the metastasis potential in human NPC CNE2Z cell line, the combination of HBO and 5-FU disposal also couldn't further decreased the MMP-9 and VEGF high-expression and inhibited the metastasis potential.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Fluorouracil ; therapeutic use ; Humans ; Hyperbaric Oxygenation ; Matrix Metalloproteinase 9 ; metabolism ; Nasopharyngeal Neoplasms ; pathology ; therapy ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVE: To explore the effect of early hyperbaric oxygen (HBO) on neuronal apoptosis and learning and memory in rats treated with cerebral ischemia-reperfusion injury in 30 min. METHODS: Experimental rats were randomly divided into 3 groups: a sham-operation group, a model group, and a treatment group. Cerebral ischemia-reperfusion injury model was induced by Zea Longa's method. Neurologic impairment score, apoptosis cell, and the expression of caspase-3 and Bcl-2 protein were observed. The amount across platform and the escape latency (EL) time were determined by Morris water maze. RESULTS: Neurologic impairment scores at 2 h, 1 d, 2 d, and 3 d of the model group and the treatment group were obviously higher than the sham-operation group (P<0.01), and those at 2 d and 3 d of the treatment group were obviously lower than those of the model group (P<0.05). The number of apoptosis cells and the expression of caspase-3 protein in the model group significantly increased compared with those in the sham-operation group (P<0.01), while those in the treatment group was significantly lower than the model group (P<0.01). Bcl-2 protein expression in the model group increased more obviously than that in the sham-operation group (P<0.01), and that in the treatment group was much higher than the model group (P<0.01). The EL time of the model group was much longer than that of the sham-operation group and the number across platform was obviously decreased compared with that of the sham-operation group (P<0.01), while the EL time of the treatment group was much shorter than that of the model group and the number across platform was more than that of the model group (P<0.05). CONCLUSION Early hyperbaric oxygen could inhibit nerve cell apoptosis suffered cerebral ischemia-reperfusion injury and improve the function of learning and memory.
Animals ; Apoptosis ; physiology ; Brain Ischemia ; complications ; pathology ; psychology ; therapy ; Caspase 3 ; metabolism ; Female ; Hyperbaric Oxygenation ; methods ; Learning ; Male ; Memory ; Neurons ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; pathology ; prevention & control ; psychology ; Time Factors

The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate (TMPP) in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes: intranasal (i.n.), intragastric (i.g.) and intravenous (i.v.) administration. After i.n., i.g. and i.v. administration of a single-dose at 10 mg/kg, cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals. The concentration of TMPP in the samples was analyzed by HPLC. The area under the concentration-time curve (AUC) and the ratio of the AUCbrain to the AUCplasma (drug targeting efficiency, DTE) was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration. After i.n. administration, TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex (t max=15 min). The ratio of the AUCbrain dialysates value between i.n. route and i.v. injection was 0.68, which was greater than that obtained after i.g. administration (0.43). The systemic bioavailability obtained with i.n. administration was greater than that obtained by the i.g. route (86.33% vs. 50.39%), whereas the DTE of the nasal route was 78.89%, close to that of oral administration (85.69%). These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation, and then crosses the blood-brain barrier (BBB) to reach the cerebral cortex. Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.