p38MAPK对慢性前列腺炎疼痛的影响及槲皮素的干预作用

Effects of p38MAPK on Rats with Chronic Nonbacterial Prostatitis Neuralgia and the Intervention Effect of Quercetin

目的探讨槲皮素对前列腺炎疼痛抑制作用的可能机制。方法利用同源大鼠前列腺蛋白提取液辅以弗氏完全佐剂诱导大鼠自身免疫性前列腺炎模型,槲皮素灌胃给药10周后,用HE染色法观察各组大鼠前列腺组织形态学差异;ELISA法测定各组血清中IL-8、TNF-α及内皮中性粒细胞激活肽78(endothelial neutrophil activating protein,ENA-78)的含量变化;免疫组化法测定神经生长因子(nerve growth factor,NGF)在前列腺组织内的表达;Western blotting法测定前列腺组织内基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)、磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)及总p38丝裂原活化蛋白激酶(p38MAPK)表达的变化。结果与模型对照组比较,槲皮素能不同程度减轻各组前列腺组织的炎症状况;模型对照组血清IL-8、TNF-α及ENA-78含量明显增高,槲皮素200 mg·kg?1能明显降低慢性前列腺炎大鼠血清IL-8、TNF-α及ENA-78的水平(P<0.05);200,100,50 mg·kg?1槲皮素给药均能不同程度抑制NGF在前列腺组织的原位表达;槲皮素200 mg·kg?1组与模型对照组比较,MMP-9、总p38MAPK及p-p38MAPK表达量不同程度降低。结论在大鼠慢性前列腺炎模型,p38MAPK信号转导途径被激活,槲皮素可同步降低细胞因子IL-8、TNF-α、ENA-78的含量及p38MAPK、p-p38MAPK的表达,这为槲皮素治疗前列腺炎疼痛提供一条新思路。

OBJECTIVE To explore the possible mechanism of quercetin on neuralgia in chronic nonbacterial prostatitis（CNP） rats. METHODS The CNP rat models were established by prostatic protein purification with Freund＇s completed adjuvant. The morphological differences in the prostate tissue were observed by HE staining. The changes of the content of IL-8, TNF-α and ENA-78 in serum were evaluated by ELISA. The expression of NGF were evaluated by immunohistochemistry. The expression of MMP-9, p-p38 MAPK and p38 MAPK were evaluated by Western blotting. RESULTS The pathological alterations of chronic prostatitis in quercetin groups were improved compared with model group; the content of IL-8, TNF-α and ENA-78 in model group were increased, but 200 mg·kg^-1 dose group of quercetin could obviously reduce the serumal content of IL-8, TNF-α and ENA-78; 200 mg·kg^-1 dose group of quercetin could obviously reduce prostate expression of NGF, p-p38 MAPK and p38 MAPK. CONCLUSION P38 MAPK signal pathway is activated in CNP rats. Quercetin can drcrease the content of IL-8, TNF-α and ENA-78, and down-regulate the expression of p38 MAPK and p-p38 MAPK, which may provide a new way for the treatment of nonbacterial prostatitis neuralgia.