ObjectiveTo investigate the role of NO and extracellular signal-regulated kinase (ERK) signaling pathways in the spinal cord in naloxone-induced withdrawal response in morphine-dependent rats.Methods Ninety male adult SD rats weighing 200-250 g in which IT catheters were successfully implanted without complication were randomly divided into 9 groups (n ＝ 10 each):group control (group C); group morphine dependence (group MD); group morphine withdrawal (group MW); group N(G)-nitro-L-arginine methyl ester (eNOS inhibitor) (L-NAME group) ; group 7-nitroindazole (nNOS inhibitor) (group 7-Ni) ; group aminoguanidine(iNOS inhibitor) (group AG); group U0126 (ERK signaling pathway blocker); group cremophor (solvent for 7-Ni) and group DMSO (solvent for U0126).Morphine dependence was induced by increasing doses of subcutaneous morphine for 6 days.The initial dose of morphine was 10 mg/kg twice a day and was increased by 10 mg/kg twice every other day until 50 mg/kg on the 6th day in groups MD,MW,L-NAME,7-Ni,AG,U0126,cremophor and DMSO.Morphine withdrawal response was induced by intraperitoneal (IP) naloxone 4 mg/kg at 4 h after last morphine administration in groups MW,L-NAME,7-Ni,AG,U0126,cremophor and DMSO.L-NAME 400 μg,7-Ni 400 μ g,AG 400μg,U0126 150 μg,cremopher 10 μl and DMSO 10 μl were administered IT at 30 min before naloxone administration in groups L-NAME,7-Ni,AG,U0126,cremophor and DMSO respectively.Morphine withdrawal response (0 ＝ no withdrawal response,3 ＝ severe response) and touch evoked agitation (0 ＝ no agitation,2 ＝ severe agitation) were observed and scored during 1 h after naloxone administration.The animals were then sacrificed and the spinal cord was removed for determination of the expression of iNOS,nNOS and phosphor-ERK (p-ERK) by immunohisto-chemistry and Western blot.ResultsMorphine withdrawal significantly increased withdrawal response score and touch evoked agitation score in group MW as comparedwith group MD.L-NAME,7-Ni,AG and U0126 pretreatment significantly attenuated naloxone-induced increase in withdrawal response score and touch evoked agitation score in groups L-NAME,7-Ni,AG and U0126 as compared with group MW.Morphine withdrawal significantly up-regulated the nNOS and iNOS expression in group MW compared with groups C and MD.L-NAME,7-Ni and AG pretreatment significantly down-regulated p-ERK expression in groups L-NAME,7-Ni and AG as compared with group MW.ConclusionThe interaction between NO and ERK signaling pathways may be involved in morphine withdrawal response in morphine-dependent rats.

BACKGROUND: Lung transplantation can improve quality of life of patients who get terminal pulmonary disease and also it can help to get better survival.Now it has become one of the best therapeutic methods for terminal pulmonary disease.However,limited donors leave the development of lung transplantation in dilemma.The emergence of living lobar transplantation and cadeveric lobar transplantation let this procedure much easier.OBJECTIVE: To evaluate the clinical probability of bilateral lobar transplantation.METHODS: Sequential bilateral lobar transplantation was performed for one 26 years old cystic fibrosis female.Cardiac pulmonary bypass was used during operation.Anti-rejection(Tacrolimus,mycophenolate,etc)and anti-infection was used postoperatively.RESULTS AND CONCLUSION: The recovery course postoperatively was smooth,and the recipient got out of hospital 7weeks later.Bilateral lobar transplantation could offer satisfied short-term pulmonary function.The long term results should be further evaluated.