Objective： To observe the effects of p38 mitogen activated protein kinase （MAPK） inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone canc...Objective： To observe the effects of p38 mitogen activated protein kinase （MAPK） inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods： Eleven rats were used to establish the models of bone cancer pain, six rats were treated by intrathecal SB203580 injection, and the other 5 were as the controls. The paw withdrawal latency （PWL）, histology and the spinal levels of IL-1β and TNF-α were detected. Results： All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However, following intrathecal injection of SB203580, the left PWLs （12.12± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days） were significant higher than that of controls （9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days）, P 〈 0.05. Meanwhile, inkathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion： Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity, which might result from inhibiting inkacellular p38 MAPK signaling transduction, and thereby reducing the release of the proinflammatory cytokines.展开更多
目的:在动物模型NOD(非肥胖型糖尿病)鼠中,观察研究Toll样受体9(Toll Like Receptor 9,TLR9)依赖的p38MAPK信号通路在原发性舍格伦综合征发病机制中的作用。方法:实验选取5周龄的雌性NOD小鼠,分别给予3种抑制剂:ODN2088、VX-792、羟氯...目的:在动物模型NOD(非肥胖型糖尿病)鼠中,观察研究Toll样受体9(Toll Like Receptor 9,TLR9)依赖的p38MAPK信号通路在原发性舍格伦综合征发病机制中的作用。方法:实验选取5周龄的雌性NOD小鼠,分别给予3种抑制剂:ODN2088、VX-792、羟氯喹。利用流式细胞学技术检测小鼠外周血淋巴细胞的情况。利用免疫组化检测小鼠下颌下腺TLR9及p-p38 MAPK的表达情况。利用酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)检测小鼠外周血中血浆抗体的表达。利用Tunel方法检测小鼠下颌下腺腺上皮细胞的凋亡。同时,观察小鼠刺激性唾液流率的改变以及下颌下腺病理学改变。结果:只有ODN2088组的NOD小鼠的唾液流率显著增加。在所有被给予羟氯喹的NOD鼠和未接受治疗的NOD鼠中,下颌下腺均有淋巴细胞浸润灶的出现。但在ODN2088组中,只有1只NOD小鼠出现下颌下腺的淋巴细胞浸润灶。在VX-702组中,所有NOD小鼠均未发现淋巴细胞浸润灶。所有实验组的外周血淋巴细胞的数目显著减少。ODN2088组NOD小鼠的抗SSA/Ro抗体和抗SSB/La抗体的浓度是所有实验组中最低的。结论:TLR9依赖的p38MAPK信号通路的抑制,能一定程度上减轻原发性舍格伦综合征动物模型NOD鼠的临床表现。展开更多
A new series of compounds, 1-aryl-3-（3,4-dihydro-2H-chromen-5-yl） ureas, have been synthesized and their structures were confirmed by FAB-MS and IH NMR. The preliminary pharmacological screening showed that these co...A new series of compounds, 1-aryl-3-（3,4-dihydro-2H-chromen-5-yl） ureas, have been synthesized and their structures were confirmed by FAB-MS and IH NMR. The preliminary pharmacological screening showed that these compounds inhibited TNF-α production in lipopolysaccharide （LPS）-stimulated THP-1 cells.展开更多
基金a grant from the National Nature Sciences Foundation of China (No. 30672426).
文摘Objective： To observe the effects of p38 mitogen activated protein kinase （MAPK） inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods： Eleven rats were used to establish the models of bone cancer pain, six rats were treated by intrathecal SB203580 injection, and the other 5 were as the controls. The paw withdrawal latency （PWL）, histology and the spinal levels of IL-1β and TNF-α were detected. Results： All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However, following intrathecal injection of SB203580, the left PWLs （12.12± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days） were significant higher than that of controls （9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days）, P 〈 0.05. Meanwhile, inkathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion： Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity, which might result from inhibiting inkacellular p38 MAPK signaling transduction, and thereby reducing the release of the proinflammatory cytokines.
文摘A new series of compounds, 1-aryl-3-（3,4-dihydro-2H-chromen-5-yl） ureas, have been synthesized and their structures were confirmed by FAB-MS and IH NMR. The preliminary pharmacological screening showed that these compounds inhibited TNF-α production in lipopolysaccharide （LPS）-stimulated THP-1 cells.
