摘要
目的探讨丹皮酚(Paeonol)对骨癌痛大鼠的镇痛作用及其可能作用机制。方法通过左后肢胫骨注射Walker256乳腺癌细胞悬液的方法建立大鼠骨癌痛模型。观察各组大鼠机械缩足反射阈值变化;qPCR检测各组大鼠脊髓处miR-21表达情况;酶联免疫吸附法(ELISA)检测各组大鼠脊髓中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的含量;Western blot检测各组大鼠脊髓中p-JNK、JNK、p-ERK、ERK、p-p38和p38蛋白表达。结果丹皮酚能明显升高骨癌痛大鼠机械缩足反射阈值,抑制骨癌痛大鼠脊髓处miR-21的表达,同时抑制炎症因子TNF-α、IL-1β及IL-6的释放,抑制大鼠脊髓中p38、p-JNK和p-ERK蛋白表达(P<0.05)。miR-21抑制剂协同丹皮酚升高骨癌痛大鼠机械缩足反射阈值,抑制了炎症因子的释放以及MAPK信号通路的活化,而miR-21模拟剂能逆转丹皮酚的上述作用。结论丹皮酚可能通过抑制炎症因子释放缓解乳腺癌转型诱导的骨癌痛,其作用机制可能与抑制miR-21的表达进而抑制MAPK信号通路的活化有关。
Objective To investigate the analgesic effect of Paeonol on bone cancer pain rats and its possible mechanism. Methods A rat model of bone cancer pain was established by injecting Walker 256 breast cancer cell suspension into the tibia of the left hind limb. The mechanical threshold changes of rats in each group were observed;the expression of miR-21 in spinal cord of rats in each group was detected by qPCR;the content of TNF-α, IL-1β and IL-6 in spinal cord of rats in each group was detected by enzyme-linked immunosorbent assay(ELISA). The expression of p-JNK, JNK, p-ERK, ERK, p-p38 and p38 were detected by Western blot. Results Paeonol could significantly increase the threshold of mechanical foot retraction reflex in rats with bone cancer pain, inhibit the release of TNF-α, IL-1β and IL-6, inhibit the expression of p38, p-JNK and p-ERK protein in the spinal cord of rats with bone cancer pain. Moreover, the use of miR-21 inhibitors in combination with paeonol increased the threshold of mechanical foot retraction reflex, inhibited the release of inflammatory factors and activation of MAPK signaling pathway, while miR-21 agonist could reverse the above effects of paeonol. Conclusion Paeonol may alleviate bone cancer pain induced by breast cancer transformation by inhibiting the release of inflammatory factors, and its mechanism may be related to inhibiting the expression of miR-21 and reducing the activation of MAPK signaling pathway.
作者
焦美
雷建军
张志成
周南
JIAO Mei;LEI Jian-jun;ZHANG Zhi-cheng;ZHOU Nan(Department of Pharmacy,The First Affiliated Hospital of China Medical University,Shenyang 110001;Laboratory of Experimental Animals,General Hospital of the Northern Theater Command,Shenyang 110016;Department of Anesthesiology,General Hospital of the Northern Theater Command,Shenyang 110016,China)
出处
《解剖科学进展》
CAS
2021年第4期453-457,共5页
Progress of Anatomical Sciences
基金
辽宁省自然基金(20180551091)。
