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Objective To evaluate the changes in the activity of extracellular signal-regulated kinase 5 (ERK5) in the distal cerebrospinal fluid contacting neurons (CSF-CNs) in the mid-brain of morphine dependent rats.Methods Forty-eight male adult Sprague-Dawley rats weighing 230-270 g,were randomly divided into 2 groups (n =24 each) using a random number table:control group (group A) and morphine dependence group (group B).Morphine dependence was induced by increasing doses of subautaneous morphine for 5 consecutive days.The initial dose of morphine was 10 mg/kg twice a day and was increased by 10 mg/kg everyday until 50 mg/kg on 5th dav.The equal volume of normal saline was injected subcutaneously instead of morphine in group A.On 3rd day after morphine dependence was induced,the distal CSF-CNs in the mid-brain was labeled with 30％ cholera toxin subunit B and horseradish peroxidase compound (CB-HRP) 3 μl injected in the lateral cerebral ventricle in the morning.At 4 h after the last injection of morphine,the segments in which CSF-CNs were located were removed,and CB-HRP positive neurons,phosphor-ERK5 (p-ERK5) positive neurons and CB-HRP/p-ERK5 positive neurons were counted.Results Compared with group A,the number of p-ERK5 and CB-HRP/p-ERK5 positive neurons in the mid-brain was significantly increased (P ＜ 0.05),and no significant change was found in CB-HRP positive neurons in group B (P ＞ 0.05).Conclusion The enhanced activity of ERK5 in the distal CSFCNs in the mid-brain may contribute to the development of morphine dependence in rats.
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Objective To evaluate the role of spinal neuronal extracellular signal-regulated protein kinases 5/cAMP response element binding protein (ERK5/CREB) signaling pathway in withdrawal responses in morphinedependent rats.Methods Ninety-six adult male Sprague-Dawley rats in which intrathecal catheters were successfully placed,weighing 200-250 g,were randomly divided into 4 groups (n =24 each):normal control group (group A),morphine withdrawal group (group B),dimethyl sulfoxide (DMSO) + morphine withdrawal group (group C) and ERK5 inhibitor BIX02188 + morphine withdrawal group (group D).Morphine dependence (MD) was induced by increasing doses of subcutaneous morphine for 6 days.The initial dose of morphine was 10 mg/kg once a day and was increased by 10 mg/kg once a day from 2nd to 5th days until 50 mg/kg on 6th day in B,C and D groups.Morphine withdrawal response (MW) was induced by intraperitoneal naloxone 4 mg/kg at 4 h after last morphine administration in B,C and D groups.In addition,BIX02188 10 μg and 1％ DMSO 10 μl were injected intrathecally at 1 h before naloxone injection in D and C groups,respectively.MW and morphine withdrawal-induced hyperalgesia were scored.The rats were then sacrificed after hyperalgesia was scored and the spinal cord was removed for determination of CREB and phosphorylated CREB (p-CREB) expression.Results Compared with group A,MW and hyperalgesia scores were significantly increased and the expression of p-CREB was up-regulated in B,C and D groups.Compared with group B,MW and hyperalgesia scores were significantly decreased and the expression of p-CREB was down-regulated in D group,and no significant change was found in group C.Conclusion The spinal neuronal ERK5/CREB signaling pathway is involved in withdrawal responses in morphine-dependent rats.
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Objective To investigate the roles of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 signaling pathway in naloxone-induced withdrawal response in morphine-dependent rats.Methods Ninety-six adult male SD rats weighting 230-250 g were randomly divided into 4 groups:control group,withdrawal group,DMSO group and MK801 group.Rats were subcutaneously injected with morphine.On day 6,rats were injected with naloxone (intraperitoneal) to precipitate morphine withdrawal syndromes.To identify the function of NMDAR-ERK5 signaling pathway in morphine withdrawal,morphine withdrawal-like behavior test and western blot technique were used in this research.The scores of morphine withdrawal symptom,morphine withdrawal-induced allodynia and the activation of ERK5 in spinal cord were observed after intrathecal injection of MK801.Results There was no withdrawal symptoms and withdrawal-induced allodynia in group A after intraperitoneal injection of naloxone.Compared with group A,withdrawal score (45.2±7.3),score of withdrawal-induced allodynia (14.4±3.7) of group B,withdrawal score (44.7±6.2),score of withdrawal-induced allodynia (13.2±2.7) of group C and withdrawal score (28.3±1.6),score of withdrawal-induced allodynia (5.9± 1.1) of group D were significantly increased (P＜ 0.05).Compared with group C,the total withdrawal score (28.3 ± 1.6),score of withdrawal-induced allodynia (5.9± 1.1) of group D were significantly decreased (P＜0.05).Compared with group A,the expression of spinal p-ERK5 of group B (12848±621) and group C (12579±396) were significantly increased (P＜0.05).Compared with group C,the expression of spinal p-ERK5 of group D (5 123±546) was significantly decreased (P＜0.05).Condusion The signaling pathway of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 contributes to naloxone-induced withdrawal response in morphine-dependent rats.
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Objective To investigate the roles of spinal extracellular signal-regulated protein kinases 5 (ERK5) on morphine withdrawal in rats.Methods Ninety-six male and adult SD rats weighting 230-250 g were randomly divided into saline-naloxone-DMSO group (group A),saline-naloxone-BIX02188 group (group B),morphine-naloxone-DMSO group (group C) and morphine-naloxone-BIX02188 group (group D).To set up morphine dependent model,rats were subcutaneously injected with morphine in the increasing dosage method.On day 6,4 h after the injection of morphine,rats were injected with naloxone (intraperitoneal) to precipitate morphine withdrawal syndrome.The scores of morphine withdrawal symptom and morphine withdrawal-induced allodynia were observed after intrathecal injection of ERK5 inhibitor BIX02188.Result There were not withdrawal symptoms and withdrawal-induced allodynia in group A and B after intraperitoneal injection of naloxone.Compared with group A,teeth chatting (7.5± 1.1),wet dog shacks (4.6± 0.7),jump (5.3± 0.7),abnormal position (8.9± 1.9),diarrhea (7.1 ± 1.6),salivation (2.8±0.6),weight loss (7.9±0.9),total withdrawal score (44.8±5.9),score of withdrawalinduced allodynia (14.6±2.4) of group C and teeth chatting (3.1±0.5),wet dog shacks (1.5±0.4),jump (2.2± 0.5),abnormal position (7.9± 1.6),diarrhea (1.8±0.5),salivation (2.8±0.9),weight loss (3.7±0.6),total withdrawal score (23.1± 1.3) and score of withdrawal-induced allodynia (3.5± 1.1) of group D were significantly increased (P＜0.05).Compared with group C,teeth chatting (3.1±0.5),wet dog shacks (1.5±0.4),jump (2.2±0.5),diarrhea (1.8±0.5),weigbt loss (3.7±0.6) and total withdirawal score (23.1±1.3),score of withdrawal-induced allodynia (3.5±1.1) of group D were significantly decreased (P＜0.05).But there was not significant change in abnoral position (7.9±1.6) and salivation (2.8±0.9).Conclusion Inhibition of the activation of spinal cord ERK5 can significantly alleviate withdrawal symptoms of morphine dependent rats by intrathecal injection BIX02188.
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Objective To evaluate the role of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord in withdrawal responses in morphine-dependent rats.Methods Ninety-six adult male SpragueDawley rats in which intrathecal catheters were successfully placed,weighing 200-250 g,were randomly divided into 4 groups (n =24 each) using a random number table:normal saline group (group A),withdrawal group (group B),dimethyl sulfoxide (DMSO) group (group C) and ERK5 inhibitor BIX02188 group (group D).Morphine dependence (MD) was induced by increasing doses of subcutaneous morphine for 6 days.The initial dose of morphine was 10 mg/kg once a day and was increased by 10 mg/kg once a day from the 2nd to 5th days until 50 mg/kg on the 6th day in B,C and D groups.Morphine withdrawal response (MW) was induced by intraperitoneal naloxone 4 mg/kg at 4 h after last morphine administration in B,C and D groups.In addition,BIX02188 and 1％ DMSO 10 μl were injected intrathecally at 1 h before naloxone injection in D and C groups,respectively.MW and morphine withdrawal-induced hypemlgesia were scored.The rats were then sacrificed after hyperalgesia was scored and the spinal cord was removed for determination of ERK5 and phosphorylated ERK5 (p-ERK5) expression.Results Compared with group A,MW and hyperalgesia scores were significantly increased and the expression of pERK5 was up-regulated in B,C and D groups (P ＜ 0.05).Compared with group B,MW and hyperalgesia scores were significantly decreased and the expression of p-ERK5 was down-regulated in D group (P ＜ 0.05),and no significant change was found in group C (P ＞ 0.05).Conclusion ERK5 in the spinal cord is involved in withdrawal responses in morphine-dependent rats.
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Objective To judge the effect of plasma exchange (PE) to the patients with severe hepatopath of nonage according to evaluating the change of the liver function of reserve with 13C-methacetin breath test. Methods There are two groups: the case group and the control group. Each group has 30 patients. The patients in the case group were treated by PE. All the patients received 13C-methacetin breath test at before or one week after treatment. MVmax40, CUM40 and CUM120 were present. At the same time, clinical symptoms, glutamate-pyruvate transaminase (ALT), total bilirubin (TBiL) and prethrombin active (PTA) were observed. Results MVmax40, CUM40, CUM120 and PTA were higher, ALT and TBiL were lower in the case group after treatment (t=4.679, 4.752, 5.048, 5.413, 6.208, 7.413, P=0.000,P<0.01). After a week, MVmax40, CUM40, CUM120 and PTA were higher, ALT and TBiL were lower in the case group than that in the control group (t=2.260, 2.247, 2.476, 4.017, 3.250, 3.658, P<0.05). The total effective rates in the case group and the control group were 83.3 % (25/30) and 43.3 % (13/30),which are significant different(χ2 10.335,P<0.01). Conclusion PE can im-prove the liver reservation functionin the severe hepatopath of nonage.
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Objective To explore the clinical effect of cholangioscopic Holmium laser lithotripsy for bile duct refractory residual stone and orthomorphia for intrahepatic bile duct membranous stenosis. Methods The final diagnosis was established by T tube retrograde cholangiography and cholangioscopy in 12 patients with refractory bile duct residual stone. Twenty-nine stones distribute in extrahepatic and intrahepatic bile duct and 5 intrahepatic bile duct membraneous stenosis were found in 3 cases. All patients underwent Holmium laser lithotripsy and orthomorphia. Results The stone clearance rate was 100% in 12 patients after cholangioscopic holmium laser lithotripsy. No serious complication occurred in patients after 5 membranous stenosis orthomorphia. Follow-up observation on 11 patients shows no obvious recurrence of symptom and stones. Conclusion Holmium laser lithotripsy and orthomorphia are safe and effective in the treatment of bile duct refractory residual stone and stenosis.