摘要
目的：探讨脊髓背角小胶质细胞上酪氨酸家族激酶（SFKs）在糖尿病神经痛中的作用。方法：采用雄性SD大鼠,体重200~220 g,免疫荧光单染检测腹腔注射链脲佐菌素（STZ）后7、14、28 d脊髓背角p-SFKs的表达水平,双染观察其表达部位;同时在给予STZ前鞘内注射SFKs抑制剂PP2,行为学检测大鼠50%机械撤足阈值的变化。结果 ：与对照组比较,腹腔注射STZ后第1天,大鼠血糖水平开始升高（P〈0.001）,持续至少28 d（P〈0.001）;机械痛撤足逐渐下降（P〈0.05）,28 d达到最低（P〈0.001）;同时腹腔注射STZ后7、14、28 d,脊髓背角p-SFKs的表达水平明显升高（均P〈0.01）;只表达于小胶质细胞中,神经元和星型胶质细胞中无表达。腹腔给予STZ前鞘内注射PP2可防止STZ诱导的机械痛敏。结论：脊髓背角小胶质细胞SFKs可能在糖尿病神经痛中发挥重要作用。
Objective To explore the roles of spinal microglial Src-family kinases（SFKs） in diabetic neuropathic pain. Methods Male Sprague-Dawley rats, weighing 200 ~ 220 g, were used in the experiments.The level of p-SFKs in spinal dorsal horn was detected by single immunofluorescence staining on day 7th, 14 th and 28 th after intraperitoneally injection of Streptozotocin（STZ） and its location was detected by double immunofluorescence staining. The changes of 50% paw-withdrawal thresholds of rat were detected by behavioral tests when PP2, a specific inhibitor of SFKs, was intrathecally administered before intraperitoneally injection of STZ. Results Compared with vehicle group, the blood glucose level increased on day 1（P 0.001） and the hyperglycemia persisted at least for 28 days（P 0.001） after intraperitoneally administered of STZ（50 mg / kg）.Paw-withdrawal threshold（PWT） decreased gradually from day 1（P 0.05） and reached the minimum on day28（P 0.001） after STZ administration. Meanwhile, the expression of p-SFKs in spinal dorsal horn markedly increased on day 7（P 0.01）, day 14（P 0.01） and day 28（P 0.01）. The p-SFKs was mainly colocalized only with microglia, but not with neurons or with astrocytes. Intrathecally administered of PP2 before STZ reversed STZ-induced mechanical hyperalgesia. Conclusion Microglial SFKs in spinal dorsal horn maybe play a pivotal role in diabetic neuropathic pain.
出处
《实用医学杂志》
CAS
北大核心
2016年第16期2594-2598,共5页
The Journal of Practical Medicine
基金
国家自然科学基金资助项目(编号:31100805)
广州市珠江科技新星项目(编号:2012J2200036)
广州市西医一般引导项目(编号:20141A011081)
