| 李 洁,刘晓宇,毛培军,刘立栋,叶 欣,吴大方,邵 英.大鼠脊髓小胶质细胞P2X4的表达和糖尿病病理性神经痛大鼠炎症反应和疼痛阈值的关系[J].,2022,(12):2232-2236 |
| 大鼠脊髓小胶质细胞P2X4的表达和糖尿病病理性神经痛大鼠炎症反应和疼痛阈值的关系 |
| The Relationship between the Expression of P2X4 in Rat Spinal Cord Microglia and the Inflammatory Response and Pain Threshold in Rats with Diabetic Pathological Neuralgia |
| 投稿时间：2022-01-09 修订日期：2022-01-31 |
| DOI：10.13241/j.cnki.pmb.2022.12.007 |
| 中文关键词: 脊髓小胶质细胞 P2X4 糖尿病 神经性疼痛 疼痛阈值 |
| 英文关键词: Spinal cord microglia P2X4 Diabetes Neuropathic pain Pain threshold |
| 基金项目:陕西省卫生健康委科研基金项目（2018D089）；陕西省自然科学基础研究计划一般项目（2019JM-422） |
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| 中文摘要: |
| 摘要 目的：探究大鼠脊髓小胶质细胞P2X4的表达和糖尿病病理性神经痛大鼠炎症反应和疼痛阈值的关系。方法：通过高脂饮食结合链脲佐菌素注射诱导糖尿病病理性神经痛大鼠模型并分为3组：对照组（正常大鼠，腹腔注射载体柠檬酸盐缓冲液0.25 mL/kg），模型组（糖尿病病理性疼痛模型，同上注射，n=15）和抑制剂组（大鼠糖尿病病理性模型，过鞘内导管注射米诺环素），共28 d。通过MWT评估对机械刺激的手掌反应。通过双极针电极检测实验大鼠的运动神经传导速速。通过蛋白印迹分析P2X4和BDNF蛋白表达。通过RT-PCR分析炎症因子IL-1β、TNF-α和NLRP3的mRNA表达。通过蛋白印迹分析p38MAPK和p-p38MAPK的蛋白表达。结果：第2week、4week和6week，模型组MWT较对照组降低（P<0.05），抑制剂组MWT较模型组升高（P<0.05）。第2 week，个实验组大鼠MNCV比较无差异（P>0.05），第4week和第6week，模型组MNCV较对照组降低（P<0.05），抑制剂组MNCV较模型组升高（P<0.05）。模型组P2X4和BDNF蛋白表达较对照组升高（P<0.05），抑制剂组P2X4和BDNF蛋白表达较模型组降低（P<0.05），模型组P2X4和BDNF mRNA表达较对照组升高（P<0.05），抑制剂组P2X4和BDNF mRNA表达较模型组降低（P<0.05）。模型组IL-1β、TNF-α和NLRP3的mRNA表达较对照组升高（P<0.05），抑制剂组IL-1β、TNF-α和NLRP3的mRNA表达较抑制剂组降低（P<0.05）。模型组p-p38MAPK蛋白表达较对照组升高（P<0.05），抑制剂组p-p38MAPK蛋白表达较模型组降低（P<0.05），各实验组大鼠p38MAPK蛋白表达无差异（P>0.05）。结论：大鼠脊髓小胶质细胞P2X4-BDNF信号在DNP中起重要作用，并且P2X4在DNP期间激活的脊髓小胶质细胞中表达升高，抑制小胶质细胞激活能显著降低P2X4表达和炎症水平，可防止热痛觉过敏并增加大鼠疼痛阈值。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the relationship between the expression of P2X4 in spinal cord microglia and the inflammatory response and pain threshold in rats with diabetic pathological neuralgia. Methods: The rat model of diabetic pathological neuralgia was induced by high-fat diet combined with streptozotocin injection and divided into 3 groups: control group (normal rats, intraperitoneal injection of vehicle citrate buffer 0.25 mL/kg), model group (diabetic pathological pain model, injected as above, n=15) and inhibitor group (rat diabetic pathological model, injected with minocycline through intrathecal catheter), for a total of 28 days. The mechanical withdrawal threshold is used to evaluate the palm response to mechanical stimuli. The motor nerve conduction velocity of experimental rats was detected by bipolar needle electrodes. The protein expression of P2X4 and BDNF was analyzed by Western blot. The mRNA expression of inflammatory factors IL-1β, TNF-α and NLRP3 were analyzed by RT-PCR. The protein expression of p38MAPK and p-p38MAPK was analyzed by Western blot. Results: In the 2nd week, 4th week and 6 th week, the MWT of the model group was lower than that of the control group (P<0.05), and the MWT of the inhibitor group was higher than that of the model group (P<0.05). In the second week, there was no difference in MNCV of rats in the experimental group (P>0.05). In the 4th and 6th weeks, the MNCV of the model group was lower than that of the control group (P<0.05), and the MNCV of the inhibitor group was higher than that of the model group (P<0.05) ). The expression of P2X4 and BDNF protein in the model group was higher than that in the control group (P<0.05), and the expression of P2X4 and BDNF protein in the inhibitor group was lower than that in the model group (P<0.05). The expression of P2X4 and BDNF mRNA in the model group was higher than that in the control group (P<0.05), and the expression of P2X4 and BDNF mRNA in the inhibitor group was lower than that in the model group (P<0.05). The mRNA expression of IL-1β, TNF-α and NLRP3 in the model group was higher than that in the control group (P<0.05), and the mRNA expression of IL-1β, TNF-α and NLRP3 in the inhibitor group was lower than that in the inhibitor group (P<0.05). The expression of p-p38MAPK protein in the model group was higher than that in the control group (P<0.05), and the expression of p-p38MAPK protein in the inhibitor group was lower than that in the model group (P<0.05). There was no difference in the expression of p38MAPK protein in each experimental group (P>0.05). Conclusion: The P2X4-BDNF signal of rat spinal cord microglia plays an important role in DNP, and the expression of P2X4 is increased in spinal microglia activated during DNP. Inhibition of microglia activation can significantly reduce P2X4 expression and inflammation Level, can prevent thermal hyperalgesia and increase the pain threshold of rats. |
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