|
|
|
| Analgesic Effect and Mechanism of Ulinastatin on Neuropathic Pain Rat Model Based on CN / IL-10 Signaling Pathway |
| HUANG Yuyuan, WEI Xuemei, ZHENG Yuxiu, et al |
| The Second Affiliated Hospital of Hainan Medical College, Hainan Haikou 570311, China |
|
|
|
|
Abstract Objective: To investigate the analgesic effect of ulinastatin (UTI) on rat model of neuropathic pain and its related molecular mechanism. Methods: Forty SD rats were randomly divided into sham group, CCI group, UTI group and UTI + Tacrolimus (FK506) group, with 10 rats in each group. Except sham group, chronic constriction injury (CCI) model was established in other groups, after the rats in each group were given the corresponding treatment, the changes of pain behavior were measured by pain behavior measurement, the morphological changes of sciatic nerve tissue were detected by hematoxylin eosin (HE) staining, and the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor- α(TNF- α) in sciatic nerve tissue were detected by enzyme-linked immunosorbent assay (ELISA); TdT-mediated dUTP nick end labeling (TUNEL) was used to detect the apoptosis of rat sciatic nerve; Western blot was used to detect the protein expression of calcineurin (CN) and interleukin-10 (IL-10). Results: UTI can reduce CCI induced neuropathic pain in rats, alleviate the pathological injury of sciatic nerve tissue, and reduce the levels of IL-6, IL-1β and TNF-α in sciatic nerve tissue, and decrease the number of apoptosis of sciatic nerve cells, the expression of CN and IL-10 protein in sciatic nerve tissue of rats with neuropathic pain was significantly up-regulated, the difference was statistically significant (P<0.05). FK506, an inhibitor of CN, attenuated the effect of UTI on neuropathic pain rats, and down-regulated the protein expression of CN and IL-10 in sciatic nerve tissue of neuropathic pain rats, the difference was statistically significant (P<0.05). Conclusion: UTI may reduce inflammation and apoptosis in neuropathic pain rats by regulating CN/IL-10 signaling pathway, and then alleviate the neuropathic pain of rats.
|
|
|
|
|
|
[1] Yin D,Chen Y,Li Y,et al.Interleukin-1 receptor associated kinase 1 mediates the maintenance of neuropathic pain after chronic constriction injury in rats[J].Neurochem Res,2019,44(5):1214~1227.
[2] 付翘楚,任丽芳,田玉科.桔梗皂苷D对大鼠神经病理性疼痛及脊髓小胶质细胞活化的影响[J].国际麻醉学与复苏杂志,2021,42(1):15~20.
[3] Song D,Song G,Niu Y,et al.Ulinastatin activates haem oxygenase 1 antioxidant pathway and attenuates allergic inflammation[J].Br Pharmacol,2014,171(19):4399~412.
[4] Lv B,Jiang XM,Wang DW,et al.Protective effects and mechanisms of action of ulinastatin against cerebral ischemia-reperfusion injury[J].Curr Pharm Des,2020,26(27):3332~3340.
[5] 张秀娟,郭铁成.多种神经病理性疼痛大鼠模型的对比评价[J].中华物理医学与康复杂志,2020,42(8):755~759.
[6] 赵丽,王胜.乌司他丁脏器保护机制的研究进展[J].中华重症医学电子杂志(网络版),2019,5(3):274~277.
[7] Nie B,Zhang S,Huang Z,et al.Synergistic interaction between dexmedetomidine and ulinastatin against vincristine-induced neuropathic pain in rats[J].Pain,2017,18(11):1354~1364.
[8] Yang QQ,Li HN,Zhang ST,et al.Red nucleus IL-6 mediates the maintenance of neuropathic pain by inducing the productions of TNF-α and IL-1β through the JAK2/STAT3 and ERK signaling pathways[J].Neuropathology,2020,40(4):347~357.
[9] Hu Q,Fang L,Li F,et al.Hyperbaric oxygenation treatment alleviates CCI-induced neuropathic pain and decreases spinal apoptosis[J].Eur Pain,2015,19(7):920~928.
[10] Miletic G,Lippitt JA,Sullivan KM,et al.Loss of calcineurin in the spinal dorsal horn contributes to neuropathic pain,and intrathecal administration of the phosphatase provides prolonged analgesia[J].Pain,2013,154(10):2024~2033.
[11] Boubali S,Liopeta K,Virgilio L,et al.Calcium/calmodulin-dependent protein kinase II regulates IL-10 production by human T lymphocytes:a distinct target in the calcium dependent pathway[J].Mol Immunol,2012,52(2):51~60.
[12] 冯亚平,丁有权,任弘毅,等.早期系统性给予IL-10对成年大鼠胫神经损伤后神经病理性疼痛的抑制作用[J].四川大学学报(医学版),2016,47(5):636~641,664. |
|
|
|
2022, Vol. 28 
