风湿祛痛胶囊对完全弗氏佐剂致慢性炎症痛小鼠的镇痛作用

Analgesic effect of Fengshi Qutong Capsules on mice with chronic inflammatory pain caused by complete Freund′s adjuvant

观察风湿祛痛胶囊(FSQTC)对慢性炎症痛小鼠的镇痛作用,以及对p-ERK/COX-2信号分子活性的影响。采用完全弗氏佐剂(CFA)诱导小鼠建立慢性炎症痛模型,分为7组:正常组,模型组,模型+FSQTC不同剂量(0.3,0.6,1.2 g·kg^-1)组,模型+阳性对照药布洛芬(IBP)0.34 g·kg^-1组,正常+FSQTC 1.2 g·kg^-1组,每日1次经口灌服FSQTC或IBP,标准Von Frey纤维评价机械痛阈值,用丙酮刺激小鼠致炎足底观察冷刺激诱发痛的反应评分,观察第1或2天给药前和给药后1,2,3,4,6 h以及第3~7天给药后3 h的机械痛阈值和冷痛敏反应评分,酶联免疫吸附法、Western blot法、免疫组化和免疫荧光法分别检测致炎足和腰4~5脊髓中PGE2,COX-1,COX-2和p-ERK的蛋白表达水平。结果显示,与正常组相比,模型组小鼠机械痛阈值降低而冷刺激反应评分升高,0.3,0.6,1.2 g·kg^-1 FSQTC给药后可剂量依赖地升高模型小鼠的机械痛阈值和降低冷刺激反应评分,作用持续6 h,其中3 h作用最显著,IBP的作用与中剂量组相近。此外,FSQTC能降低模型组小鼠致炎足和/或脊髓中异常增高的PGE2,COX-2及p-ERK蛋白含量,以中、高剂量组作用明显,但对COX-1则没有明显影响,而IBP在抑制这些分子的同时也抑制了COX-1的含量。提示了FSQTC对慢性炎症痛模型小鼠具有明显的镇痛作用,且这一作用可能与对p-ERK/COX-2信号通路的抑制有关。

The aim was to observe the analgesic effect of Fengshi Qutong Capsules(FSQTC)on chronic inflammatory pain in mice,and investigate its effect on p-ERK/COX-2 signal molecular activity.A model of chronic inflammatory pain was induced in mice by complete Freund′s adjuvant(CFA).The mice were divided into normal control group,model group,model+FSQTC 0.3,0.6 and 1.2 g·kg^-1 groups,model+positive control drug ibuprofen(IBP,0.34 mg·kg^-1·d-1)group,and normal control+FSQTC 1.2 g·kg^-1group.FSQTC or IBP was given once a day by oral administration.Standard Von Frey fiber was used to evaluate the mechanical pain threshold,and the acetone stimulation was used to induce inflammatory plantar and observe the cold pain reaction scores.The mechanical pain threshold and cold pain reaction scores were observed before administration and 1,2,3,4,6 h after administration on the first day,as well as 3 h after administration on the 3 rd to 7 th day.The protein levels of PGE2,COXs-1,2 and p-ERK in the spinal cord of the inflammatory foot and lumbar 4-5 were detected by enzyme-linked immunosorbent assay,Western blot,immunohistochemistry and immunofluorescence.The results showed that the mechanical pain threshold of the model group decreased and the cold pain reaction score increased as compared with the normal group.FSQTC application could dose-dependently increase the mechanical pain threshold and decrease the cold pain reaction score.The effect lasted for 6 h,most significant at 3 h.The effect of ibuprofen was similar to that of the 0.6 g·kg^-1 dose group.In addition,FSQTC could reduce the abnormally increased protein content of PGE2,COX-2 and p-ERK in the inflammatory foot and/or spinal cord of the model group,and the effect was most significant in middle and high dose groups.However,it had no effect on COX-1 in the inflammatory foot and spinal cord of mice.The results suggest that FSQTC has ob-vious analgesic effect on chronic inflammatory pain in mice,which may be related to inhibition of p-ERK/COX-2 signaling pathway.