鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内联合应用白细胞介素-1受体拮抗剂、氯胺酮对慢性神经病理性疼痛的影响

objective To observe the effect of intrathecal injection of IL-1ra and ketamine for chronic constriction injury (CCI)in rats. Methods 40 male SD rats were randomly divided into 5 groups: Sham operation group;CCI group; IL-1ra group;ketamine group; IL-1ra and ketamine group. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold(MWT) of 2 h pre -drug and 2,4,6 h after injected drugs at day 21 in rats were performed by Hargreave's thermal radiation apparatus and von Frey's method of micro filament, respectively. The rats were killed after the behavior test was finished. The expression of p-ERK was measured in the spinal cord by immunohistochemical analysis and western blot method. Results The group of combined injection IL-1rα and ketamine produced significantly more potent analgesia compared with that of CCI group. MWT(7.1±2.2 )and TWL ( 13.5 ±3.6)were increased from 2 hours to 6 hours after intrathecal injection of IL-1rα and ketamine(P<0.01 ). The expressions of p-ERK and the number of positive cells in the combined injection group were significantly lower than that of CCI group (P<0.01). The effect of IL-1ra and ketamine in lower dosages is tendency enhanced than that of higher dosage alone. Conclusion The combined injection of IL-lra and ketamine in lower dosage can produce synergistic abirritation in chronic pain.     

Increased phosphorylation of cyclic AMP response element binding protein （CREB） in the dorsal root ganglia and superficial dorsal horn neurons following chronic constriction injury

Objective To investigate whether chronic constriction injury （CCI） of the sciatic nerve of rats could produce alterations in the phosphorylation of cyclic AMP response element binding（CREB） protein in dorsal root ganglia （DRG） and superficial dorsal horn neurons of the spinal cord. Methods Chronic constriction injury （CCI） of the sciatic nerve was employed as a model of neuropathic pain. Thirty-two Sprague-Dawley rats were randomly divided into NaYve, Sham, CCI 2w（received CCI for 2 weeks） and CCI 4w（received CCI for 4 weeks） groups. Hind paw withdrawal threshold to mechanical stimuli and withdrawal latency to thermal stimuli were used to detemline the mechanical and thermal hypemlgesia. Then all the rats were deeply anesthetized and perfused intracardiaUy with paraformaldehyde. The fixed I4-5 spinal cord and the L5 DRG ipsilateml to CCI were harvested for fixation. The pCREB-immunoreactive（pCREB-IR） cells in both DRG and superficial dorsal horn neurons were quantified for analysis using immunohistochemistry methods. Results On the 14th day after sciatic nerve injury, all the rats exhibited significant mechanical and thermal hyperalgesia. The mechanical withdrawal thresholds to yon Frey filament from CCI 2w group decreased significantly compared to both baseline values and those of Sham group（ P 〈 0.01 ） ; Thermal withdwal latencies from CCI 2w group decreased significantly compared to both baseline values and those of Sham group（ P 〈 0.01 ）. Some rats from Sham group also showed mechanical hyperalgesia compared to both baseline values and those of Naive group（ P 〈 0.01）. 28 days after CCI, both mechanical and thermal hypersensitivity were significantly alleviated, with no statistical significance compared to those of Sham group. On the 14th day after CCI, the number of pCREB-IR ceils significantly increased in ipsilateral L5 DRGs and superficial dorsal horns（ P 〈 0.01 ） compared to Sham group. The number of phosphorylated CREB-IR cells in the ipsilateral DRGs from Sham group also increased compared to that of Naive rats（ P 〈 0.05）. There were no significant statistical differences of numbers of CREB-IR neuron between Sham group and CCI 4w group. Conclusion CCI increases CREB phosphorylatian both in DRG and superficial dorsal horn neurons of the lumbar spinal cord, and may be one of the key molecular mechanisms of central and peripheral sensitization following peripheral nerve injury.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

目的 观察鞘内注射c-Jun氨基末端蛋白激酶(c-Jun N-terminal protein kinase,JNK)特异性抑制剂SP600125对慢性压榨性损伤(chronic constriction injury,CCI)大鼠痛行为的影响.方法 雄性sD大鼠40只,随机分为5组(n=8). SP5组:CCI模型,鞘内注射SP600125 5μg;SP25组:CCI模型,鞘内注射SP600125 25 μg;SP50组:CCI模型,鞘内注射SP600125 50μg;DMSO组:CCI模型,鞘内注射2%二甲亚砜溶剂10 μl;Naive组:正常大鼠,鞘内注射SP600125 50μg.SP600125均溶于2%二甲亚砜10μl.CCI模型制作7 d后行鞘内注射,并测定大鼠机械缩足反射阈值(mechanical withdrawal threshold,MWT)及热缩足反射潜伏期(thermal withdrawal latency,TWL).结果 鞘内注射SP600125对正常大鼠的痛行为无影响.鞘内注射一定剂量SP600125能减轻CCI大鼠的机械痛敏及热痛敏.结论 鞘内注射一定剂量的SP600125能够减轻CCI大鼠的机械痛敏及热痛敏.     

JNK抑制剂SP600125对骨质疏松症保护作用的实验研究

目的 探讨JNK抑制剂SP600125对骨质疏松症模型成骨细胞和破骨细胞分化及功能的影响。方法 使用CCK8试验检测RAW264.7细胞、BMMs细胞和成骨细胞的增殖活性;使用相关染色试验探究JNK抑制剂SP600125的成骨化作用和对破骨细胞分化及功能的影响;使用RT-PCR分别检测BMMs细胞中破骨细胞及成骨细胞特异性基因mRNA表达水平;使用蛋白印迹试验检测RAW264.7细胞中JNK通路和NF-κB通路的活化水平;使用DCFH-DA法检测RAW264.7细胞中ROS水平。结果 CCK8试验结果显示,当SP600125浓度≤20 μmmol/L,对RAW264.7细胞、BMMs细胞和成骨细胞的增殖活性无显著影响;SP600125不影响成骨细胞钙结节的形成并抑制破骨细胞分化和功能;SP600125抑制的破骨细胞特异性基因的表达但不改变成骨细胞特异性基因的表达;SP600125抑制RANKL诱导的RAW264.7细胞中JNK通路和NF-κB通路的激活及ROS水平的升高。结论 JNK抑制剂SP600125能够抑制破骨细胞的分化及骨吸收功能,但对成骨细胞的分化无显著影响。