京尼平苷对糖尿病大鼠神经病理性疼痛的影响

Analgesic effect of geniposide on diabetic neuropathic pain in rats

目的探讨京尼平苷对链脲佐菌素诱导的1型糖尿病性神经病理性疼痛大鼠的镇痛作用及可能作用机制。方法通过链脲佐菌素诱导的SD大鼠建立糖尿病性神经病理性疼痛模型,将大鼠随机分为对照组、模型组、阳性对照组(加巴喷丁)及不同剂量京尼平苷处理组(1,10和100mg·kg-1)。建模后第21天给予不同剂量京尼平苷,连续给药7d。免疫荧光组织化学法观察脊髓背角小胶质细胞活化情况,ELISA法观察脊髓致炎细胞因子水平。结果连续给予京尼平苷对糖尿病大鼠机械痛敏具有较好的镇痛作用,同时观察到京尼平苷可显著抑制脊髓背角小胶质细胞活化及致炎细胞因子TNF-α和IL-1β水平;同时京尼平苷可降低糖尿病大鼠的血糖水平。结论京尼平苷对糖尿病性神经病理性疼痛具有较好的镇痛作用,其机制可能与抑制脊髓背角小胶质细胞活化及致炎细胞因子水平有关。

Objective To investigate the analgesic effect of geniposide on streptozocin(STZ)induced type1diabetes rat and explore its potential pharmacological mechanism.Methods The diabetes rat model was established by injecting large dose of STZ.SD rats were randomly divided into control group,model group,positive control(gabapentin)group and geniposide group(1,10,100mg·kg-1).Geniposide was administrated for7continuous days after diabetic neuropathic pain model established for21d.The Iba-1,a biomarker of microglia activation,was observed by immunofluorescence staining in the spinal cord of rats.Enzyme-linked immunosorbent assay(ELISA)was used to evaluate the levels of pro-inflammatory cytokines.Results Repeated treatment by geniposide could significantly attenuate the STZ-induced diabetic neuropathic pain and the levels of pro-inflammatory cytokines.Furthermore,geniposide inhibited the over-activation of microglia and reduced the TNF-αand IL-1βlevel of blood glucose in diabetic rats.Conclusion Geniposide prevented STZ induced mechanical allodynia in diabetic rats,and the effect may involved in inhibiting microglia activation and decreasing the levels of pro-inflammatory cytokines.