摘要
目的观察塞来昔布对疼痛抑郁共病大鼠行为学的影响,并探索其对大鼠中缝核炎症小体NOD样受体家族3(NLRP3)、吲哚胺2,3双加氧酶(IDO)的活性及炎症因子肿瘤坏死因子α(TNF-α)的调节作用。方法15只SD雄性大鼠随机分为对照组、模型组和塞来昔布组,每组各5只,模型组、塞来昔布组大鼠每天给予腹腔注射利血平1 mg/kg,连续注射3 d,建立疼痛抑郁共病模型大鼠;对照组大鼠每天给予同体积蒸馏水;塞来昔布组于造模前1 h予25 mg/kg塞来昔布灌胃给药。应用糖水偏好实验评价实验大鼠的抑郁行为,采用智能热板仪检测各组大鼠热缩足阈值;运用q-PCR技术检测中缝核IDO及TNF-αmRNA水平;运用Western blotting技术检测中缝核NLRP3及IDO蛋白表达水平。结果与对照组[糖水偏好指数(94.60±2.07)%,热缩足阈值(9.48±1.20)s]比较,模型组大鼠糖水偏好指数[糖水偏好指数(61.20±14.17)%]明显降低(P<0.001),热缩足阈值[热缩足阈值(4.27±0.74)s]明显降低(P<0.001);与模型组比较,塞来昔布组糖水偏好指数[(92.00±5.00)%]升高,差异有统计学意义(P<0.005);与模型组比较,塞来昔布组热缩足阈值[(7.07±1.37)s]明显改善(P<0.005);与模型组[IDO mRNA(2.29±0.46),TNF-α mRNA(1.62±0.3),NLRP3蛋白表达相对灰度值(0.25±0.01),IDO蛋白表达相对灰度值(0.41±0.02)]比较,塞来昔布组大鼠中缝核IDO、TNF-α的mRNA水平[1.47±0.42,1.08±0.27]及NLRP3、IDO蛋白表达水平[0.14±0.04,0.29±0.07]降低,差异有统计学意义(P<0.05)。结论塞来昔布可以改善利血平导致的疼痛抑郁共病大鼠的行为学及改善大鼠疼痛阈值,其作用机制可能与降低中缝核炎症小体NLRP3及炎症因子TNF-α表达,抑制IDO的mRNA及蛋白表达有关。
Objective To observe effects of celecoxib on behavior and the level of NOD-like receptor family 3(NLRP3),indoleamine 2,3 dioxygenase(IDO),inflammatory factors tumor necrosis factor alpha(TNF-α)in raphe nucleus of rats with pain accompanied by depression.Methods Fifteen SD male rats were randomly divided into Con group,Res group and Res+Ce group.Rats in the Res group and Res+Ce group were intraperitoneally injected with reserpine 1 mg/(kg·d)for 3 days to establish the model.Rats in the Con group were injected with the same amount of distilled water.Rats in Res+Ce group were given by gavage with celecoxib(25 mg/kg)1 hour before modling.The sucrose preference experiment was used to evaluate the depression behavior of experimental rats.The intelligent hot plate instrument was used to detect rat heat-shrinking threshold in each group.The mRNA expression levels of IDO and TNF-αin raphe nuclei tissue were detected by q-PCR and the protein levels of NLRP3 and IDO were detected by Western blotting.Results Compared with the Con group[sucrose preference(94.60±2.07)%,the heat-shrinking threshold(9.48±1.20)s],the sucrose preference in Res group[(61.20±14.17)%]decreased(P<0.001),the heat-shrinking threshold of the rats in the Res group[(4.27±0.74)s]was significantly decreased(P<0.001).Compared with the Res group,the sucrose preference and the heat-shrinking threshold of the rats in the Res+Ce group[(92.00±5.00)%,(7.07±1.37)s]was significantly improved(P<0.005).Compared with Res group[IDO mRNA(2.29±0.46),TNF-α mRNA(1.62±0.3),NLRP3 protein expression(0.25±0.01),IDO protein expression(0.41±0.02)],the mRNA expression levels of IDO and TNF-α of Raphe Nuclei tissue in Res+Ce group[1.47±0.42,1.08±0.27]were significantly decreased(P<0.05),and the protein expression levels of NLRP3 and IDO of Raphe Nuclei tissue in Res+Ce group[0.14±0.04,0.29±0.07]were significantly decreased(P<0.05).Conclusion Celecoxib can improve the behavior and the mechanical pain threshold of the rats with pain accompanied by depression caused
作者
许丽娥
赵静洁
杜仪
吴冬月
王安娜
高雪松
李丽
王永志
XU Li-e;ZHAO Jing-jie;DU Yi(Department of Traditional Chinese Medicine,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)
出处
《临床和实验医学杂志》
2021年第1期1-4,共4页
Journal of Clinical and Experimental Medicine
基金
北京市自然科学基金项目(编号:7172063)
北京市自然基金项目(编号:7204250)
北京市市属医院科研培育计划项目(编号:PZ2017024)
北京中医药科技发展基金项目(编号:QN2018-33)。
关键词
大鼠
塞来昔布
疼痛
抑郁
共病
炎症因子
Rats
Celecoxib
Pain
Depression
Comorbidity
Inflammatory cytokines
