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Objective To evaluate the role of c-Jun N-terminal kinase (JNK) signaling pathway in paclitaxel-induced apoptosis in hippocampal neurons of rats, and the relationship with nuclear factor kappa B (NF-κB) pathway.Methods The primarily cultured hippocampal neurons were seeded in 96-well plate at a density of 1×106 cells/ml (200 μl/hole) , and were randomly divided into 4 groups (n=8 each) using a random number table: control group (C group), paclitaxel group (P group), JNK inhibitor SP600125 group (S group), and SP600125 + paclitaxel group (S+P group).Paclitaxel 2 ml (1 μmol/L) was added to group P.SP600125 2 ml (10 μmol/L) was added to group S.In group S+P, SP600125 2 ml (10 μmol/L) was added, the cell were then incubated for 1 h, and then paclitaxel 2 ml (1 μmol/L) was added.The cells were then incubated for 24 h.At 24 h of incubation, the apoptosis in hippocampal neurons was detected by flow cytometry, and the expression of NF-κB p65 was measured by Western blot.The apoptosis rate was calculated.Results Compared with group C, the apoptosis rate was significantly increased, and the expression of NF-κB p65 was up-regulated in P and S+P groups, and the apoptosis rate was significantly decreased, and the expression of NF-κB p65 was down-regulated in group S (P＜0.05).Compared with group P, the apoptosis rate was significantly decreased, and the expression of NF-κB p65 was down-regulated in group S+P (P＜0.05).Conclusion JNK signaling pathway mediates paclitaxel-induced apoptosis in hippocampal neurons of rats, and the mechanism is likely related to inhibition of NF-κB pathway activation.
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Objective To evaluate the role of M3 muscarinic acetylcholine receptor (M3 mAChR) in the release of glycinergic neurotransmitter by using oxotremorine-M (Oxo-M: a nonselective mAChR agonist) and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP: a highly selective M3mAChR antagonist). Methods Twenty male 3-4 weeks old SD rats weighing 160-180 g after successful intrathecal catheterization were randomized into 2 groups (n = 10 each): normal saline group (group NS) and pertussis toxin (group PTX).Pertussis toxin 1.5 μg/10 μl was injected IT in group PTX, while in group NS normal saline 10 μl was injected IT instead. The animals were killed at day 7 after injection. The spinal cords were removed and sliced and placed in artificial CSF. Glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) were measured in spinal lamina Ⅱneurons using whole-cell voltage-clamp technique. Five minutes after sealing, Oxo-M (final concentration 3 μ mol/L) was added. Oxo-M was then completely washed out 3 min later and 4-DAMP (final concentration 25 nmol/L) was added after 5 min of stabilization. In the presence of 4-DAMP, Oxo-M (final concentration 3 μmol/L) was added again 3 min later. sIPSCs were recorded before addition of Oxo-M (T1), 3 min after addition of Oxo-M (T2), 3 min after addition of 4-DAMP (T3), 3 min after the second addition of Oxo-M (T4). Results Compared with the baseline value at T1 , Oxo-M significantly increased the frequency of glycinergic sIPSCs at T2without changing the amplitude at T2-4 in both groups. The frequency of sIPSCs was significantly lower at T4 than at T2 in both groups (P ＜ 0.05 or 0.01). There was no significant difference in both frequency and amplitude of glycinergic sIPSCs between the two groups. Conclusion M3 mAChR plays a predominant role in the release of glycinergic transmitter in the spinal lamina Ⅱ neurons in rats.
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Objective To investigate the role of GABAB1 receptors in spinal dorsal horn neurons in the development of diabetic neuropathic pain (DNP). Methods Sixty pathogen free male SD rats aged 4 weeks weighing 150-170 g were randomly divided into 2 groups ( n = 30 each): control group and DNP group. Diabetes mellitus was induced by single intraperitoneal injection of streptozotocin 50 mg/kg. Blood glucose levels and paw withdrawal threshold to mechanical stimuli were measured at 3, 5 and 7 weeks (T1, T2, T3 ) after IP STZ/NS ( n = 10 each). The animals were sacrificed after PWL measurement. The lumbar segment of the spinal cord was removed for determination of the expression of GABAB1 receptors by immuno-histochemistry, RT-PCR and Western blot analysis. Results The blood glucose levels were significantly higher while the PWT was significantly lower at T1,T2 and T3 in group DNP than in control group. The expression of GABAB1 receptor mRNA and protein in spinal dorsal horn was significantly lower at T2 and T3 in DNP group than in control group. Conclusion The expression of GABAb1 receptors is down-regulated in spinal dorsal horn neurons in rats with DNP.
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Objective To investigate the effect of the mascarinic acetylcholine receptor (mAChR) agonist Oxo-tremorine-M (Oxo-M) on glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) and micro-inhibitory postaynaptic currents (mIPSCs) in lamina Ⅱ neurons in the spinal cord of rats. Methods Glycinergic IPSCs (sIPSCs and mIPSCs) in lamina Ⅱ neurons of spinal slices were recorded using the whole-cell voltage-clamp method. The non-selective mAchR ngonist Oxo-M was applied through bath perfusian. The effects of Oxo-M 1, 3, 5 and 10 μmol/L on sIPSCs and mIPSCs were examined. Results Oxo-M at the concentrations of 3-10 μmol/L significantly increased the frequency of sIPSCs without changing the amplitude in 16 lamina Ⅱ neurons tested. Interestingly, when the concentration of Oxo-M was increased to 10 μmol/L, the potentiating effect of Oxo-M on the frequency of slPSCs was decreased as compared with 3 μmol/L Oxo-M in the above 16 neurons. The slPSCs were completely abolished by 2 μmol/L strychnine. Atropine, the specific mAChR antagonist, completely blocked the effect of Oxo-M on the frequency of sIPSCs. In 9 additional lamina Ⅱ neurons, 1-10 μmol/L oxo-M failed to alter significantly the frequency and amplitude of glycinergic mIPSCs. Conclusion Activation of mAChRs in the somatodendritic site of glycinergic interneurous increases the synaptic glycine input to spinal dorsal horn neurons, but not in a dose-dependent manner.
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Objective To investigate the effects of propranolol on thyroid hormone in patients with hyperthyroidism after operation. Methods Forty patients with mediate or severe degree hyperthyroidism undergoing operation were randomly divided into four groups according to anesthesia and whether to take propranolol in perioperative period: Group A:propranolol plus general anesthesia; Group B: general anesthesia; Group C:propranolol plus cervical plexus blocking; Group D: cervical plexus blocking. The consecutive changes of T 3, T 4,rT 3 and TSH were measured with radioimmunological assay pre and post operatively. Results The level of serum T 3 in all groups decreased 1～7 days after operation. The decrease in serum T 3 leves was most significant 3～7 days after operation in group A and C, 1～3 days after operation in proup B and D(P
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Objective To demonstrate the incidence and relative factors of hypothyroidism after partial thyroidectomy (PTC). Methods The records of all euthyroidsm patients who underwent hemithyroidectomy from 1988 to 2000 were reviewed to determine the incidence of postoperative hypothyroidism and the predisposing factors. All the patients age, gender, serum TSH TGA and TPO levels,and the weight of resected thyroid tissue were evaluated. Hypothyroidsm patients were evaluated for the symptoms , timing of diagnosis , and thyroxine therapy. Results Hypothyroidism was diagnosed in 41(3.4%) of 1 210 patients ,inclnding subclinical hypothyroidsm in 28 and overt in 13.The mean postoperative serum TSH level was (9.22?3.36)mU/L. The mean preoperative serum TSH level was (3.14?1.05)mU/L in hypothyroidsm patients but in euthyroid patients was (1.07?0.72)mU/L(P