1.Analgesic mechanism of minocycline inhibiting activation of glial cells in rat models of trigeminal neuralgia
Yi YANG ; Chenyang HAN ; Li GUO ; Qiaobin GUAN
Chinese Journal of Neuromedicine 2018;17(7):656-661
Objective To study the mechanism of minocycline inhibiting inflammatory reaction of trigeminal ganglion glial cells in trigeminal neuralgia rats,and provide reference and support for treatment of trigeminal neuralgia.Methods (1) The rat models of trigeminal neuralgia were established by laser chemical induction oftrigeminal nerve injury.Thirty SD rats were randomly divided into sham-operated group,model Ⅰ group,minocycline group (intragastric administration of 50 μg minocycline for 7 d,n=10).The threshold of mechanical pain was measured in the facial nerve areas of rats.The protein and mRNA expressions of nuclear transcription factor (NF)-κB and interleukin (IL)-1β in the trigeminal ganglion were detected,the activation of satellite glial cells was observed by glial fibrillary acidic protein (GFAP) staining,and immunohistochemical staining was used to detect NF-κB level.(2) The inflammatory models of glial cells were established with nitroglycerin;and trigeminal glial cells from the SD rats were cultured in vitro;the cell models were divided into control group,model Ⅱ group,low-dose minocycline group (15 μmol/L),and high-dose minocycline group (30 μmol/L);the expressions of NF-κB and IL-1β in cells were detected.Fluo-3/AM probe load was used to observe the concentration changes of calcium ions in the glial cells.Results (1) The threshold of pain in trigeminal neuralgia of minocycline group was significantly higher than that of model Ⅰ group (P<0.05);the protein and mRNA expressions of NF-κB and IL-1β in the minocycline group were significantly decreased as compared with those in model Ⅰ group (P<0.05);weak NF-rB expression was noted in the sham-operated group,strong NF-κB expression was noted in the model Ⅰ group,and that in the minocycline group was obviously decreased as compared with that in model Ⅰ group;number of GFAP positive cells in the minocycline group was significantly smaller as compared with the model Ⅰ group (P<0.05).(2)The protein and mRNA expressions of NF-κB and IL-1β in the low-dose minocycline group and high-dose minocycline group were significantly decreased as compared with those in the model Ⅱ group (P<0.05);and the concentration of calcium ions in astrocytes of the low-dose minocycline group and high-dose minocycline group was significantly decreased as compared with that of model Ⅱ group (P<0.05).Conclusion Minocycline can alleviate pain in trigeminal neuralgia rats by inhibiting the activation of satellite glial cells and decreasing the levels of inflammatory factors NF-κB and IL-1β.
2.To study the correlation of peripheral blood F-box and WD repeat domain-containing domain protein7 and myeloid cell leukemia-1 expression levels with the prognosis of Icotinib administration in elderly patients with advanced non-small-cell lung cancer
Yi YANG ; Qiaobin GUAN ; Li GUO ; Chenyang HAN
Chinese Journal of Geriatrics 2018;37(8):888-891
Objective To study the correlation of the prognosis of Icotinib administration with the expression levels of F-box and WD repeat domain-containing 7(FBW7) and myeloid cell leukemia-1 (MCL-1) in peripheral blood in elderly patients with advanced non-small-cell lung cancer.Methods A total of 76 patients aged 60 years or over diagnosed with non-small-cell lung cancer(NSCLC) with EGFR-sensitive mutations and under Icotinib treatment were enrolled in this study.FBW7 and MCL-1 mRNA expression levels in peripheral blood were detected by real-time quantitative PCR(RT-QPCR).The correlation of FBW7 and MCL-1 expression levels with clinical and histological parameters,overall survival (OS),and progression-free-survival (PFS) was analyzed.Results The FBW7 expression level and the MCL-1 expression level were negative correlated(r =-0.37,P <0.001).High FBW7 expression levels and low MCL-1 expression levels in peripheral blood were associated with improved therapeutic efficacy of Icotinib (P<0.001) and extended OS and PFS.Cox regression analysis showed that the expression levels of FBW7 and MCL-1 in peripheral blood were independent influencing factors for OS and PFS.Conclusions Patients with high FBW7 expression levels and low MCl-1 expression levels are more likely to benefit from Icotinib treatment.Expression levels for either factor can be used as a predictive indicator for the effectiveness of Icotinib and provide guidance for its clinical use.