Abstract：Objective: To investigate the effect of intraperitoneal tanshinone IIA on hyperalgesia induced by vincristine in rats with neuropathic pain and its possible mechanism. Methods: A total of 40 healthy male SD rats were randomly divided into 4 groups (10 in each): control group, chemotherapy-induced neuropathic pain (CINP) group (modeled by intraperitoneal injection of vincristine every other day), CINP+NS group (Successful establishment of CINP model and intraperitoneal injection of normal saline), CINP +Tan group (Successful establishment of CINP model and intraperitoneal injection of tanshinone IIA). Mechanical allodynia and heat hyperalgesia was evaluated with thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT). Western blotting was used to detect the expression of phosphorylated c-Jun N-terminal kinase (p-JNK), glial fibrillary acidic protein (GFAP) and Ionized calcium binding adapter molecule (Iba1) in spinal cord, immunofluorescence assay to detect the Co-localization expression of GFAP and p-JNK, reverse transcription-polymerase chain reaction to detect the mRNA expression of tumor Necrosis Factor-α (TNF- α), interleukin- 6 (IL-6) and interleukin-1 (IL-1β) andenzyme-linked immunosorbent assay to detect the protein expression of TNF- α, IL-6 and IL-1β. Results: The TWL and MWT in group CINP were significantly lower those in the control group from 3 days to 14 days after the first injection of vincristine (P<0.01). The MWT and TWL in group CINP+Tan were significantly higher than those in group CINP +NS (P<0.01). Significant up- regulation was found in group CINP as compared with the control group in protein expression of p-JNK, GFAP, TNF- α, IL-6 and IL-1β and the Mrna expression of TNF- α, IL-6 and IL-1β in spinal cord (P<0.01). Significant down-regulation was observed in group CINP+Tan as compared with the CINP+NS group in the protein expression of p-JNK, GFAP, TNF- α, IL-6, IL-1β and the mRNA expression of TNF- α, IL-6 and IL-1β in the spinal cord (P<0.05). The co-localization expression of GFAP and p-JNK were observed in spinal cord. Conclusion: Tanshinone IIA can inhibit the hyperalgesia of neuropathic pain rats induced by vincristine, and its mechanism may be related to the activation of JNK pathway and inflammation of astrocytes.
付宝军, 姜静静, 黄玉琼, 林宗航, 李恒. 丹参酮ⅡA对长春新碱诱导神经病理痛大鼠痛觉过敏的影响及其机制[J]. 河北医学, 2020, 26(7): 1057-1061.
FU Baojun, JIANG Jingjing, HUANG Yuqiong, et al. Effect of Tanshinone IIA on Hyperalgesia Induced by Vincristine in Rats with Neuropathic Pain and its Mechanism. HeBei Med, 2020, 26(7): 1057-1061.
[1] 付宝军,姜静静,黄玉琼,等.丹参酮ⅡA抑制长春新碱诱导化疗痛维持期痛觉过敏及其机制[J].中国实验诊断学,2019,23(5):880~885. [2] 徐昕,唐丽玮,金丹,等.氯胺酮对腰椎间盘突出根性痛大鼠脊髓炎症因子的影响及机制[J].中国临床药理学杂志,2019,35(18):2119~2121. [3] Kong D, Guo Z, Yang W, et al. Tanshinone II A affects diabetic peripheral neuropathic pain via spinal dorsal horn neuronal circuitry by modulating endoplasmic reticulum stress pathways[J]. Experimental and Clinical Endocrinology & Diabetes, 2020, 128(1): 59~65. [4] 付宝军,姜静静,黄玉琼,等.丹参酮ⅡA对长春新碱诱导大鼠机械痛敏和热痛敏形成的影响及其机制[J].国际麻醉学与复苏杂志,2019,40(5):335~341. [5] Luo H, Liu H Z, Zhang W W, et al. Interleukin-17 regulates neuron-glial communications, synaptic transmission, and neuropathic pain after chemotherapy[J]. Cell Reports, 2019, 29(8): 2384~2397. [6] Wahlman C, Doyle T M, Little J W, et al. Chemotherapy-induced pain is promoted by enhanced spinal adenosine kinase levels through astrocyte-dependent mechanisms[J]. Pain, 2018, 159(6): 1025~1034. [7] Hao Y, Luo X, Ba X, et al. Huachansu suppresses TRPV1 up-regulation and spinal astrocyte activation to prevent oxaliplatin-induced peripheral neuropathic pain in rats[J]. Gene, 2019, 680: 43~50. [8] Yan X, Li F, Maixner D W, et al. Interleukin-1beta released by microglia initiates the enhanced glutamatergic activity in the spinal dorsal horn during paclitaxel-associated acute pain syndrome[J]. Glia, 2019, 67(3): 482~497. [9] Al Mazidi S, Alotaibi M, Nedjadi T, et al. Blocking of cytokines signalling attenuates evoked and spontaneous neuropathic pain behaviours in the paclitaxel rat model of chemotherapy-induced neuropathy[J]. European Journal of Pain, 2018, 22(4): 810~821. [10] Wu P, Chen Y. Evodiamine ameliorates paclitaxel-induced neuropathic pain by inhibiting inflammation and maintaining mitochondrial anti-oxidant functions[J]. Human cell, 2019, 32(3): 251~259. [11] Xu Y, Cheng G, Zhu Y, et al. Anti-nociceptive roles of the glia-specific metabolic inhibitor fluorocitrate in paclitaxel-evoked neuropathic pain[J]. Acta Biochimica Biophysica Sinica, 2016, 48(10): 902~908.
2020, Vol. 26 
冀公网安备13080202000677号