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穿心莲内酯调节HMGB1/RAGE信号通路对糖尿病周围神经病变大鼠坐骨神经功能损伤的影响
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| 篇名： | 穿心莲内酯调节HMGB1/RAGE信号通路对糖尿病周围神经病变大鼠坐骨神经功能损伤的影响 |
| TITLE： | Impacts of andrographolide on sciatic nerve function damage in diabetic peripheral neuropathy rats by regulating HMGB1/RAGE signaling pathway |
| 摘要： | 目的 探讨穿心莲内酯调节高迁移率族蛋白B1（HMGB1）/晚期糖基化终产物受体（RAGE）信号通路对糖尿病周围神经病变（DPN）大鼠坐骨神经功能损伤的影响。方法将84只大鼠随机分为对照组（生理盐水）、DPN组（生理盐水）、穿心莲内酯低剂量组（0.833mg/kg）、穿心莲内酯高剂量组（3.332mg/kg）、硫辛酸组（阳性对照，0.1g/kg）、重组大鼠HMGB1蛋白（rHMGB1，8μg/kg）组、穿心莲内酯高剂量+rHMGB1组，每组12只。除对照组外，其余各组大鼠均采用高糖高脂饲料喂养联合腹腔注射链脲佐菌素的方式构建DPN模型。造模成功24h后，进行给药处理，每天1次，持续8周。给药结束后，检测大鼠空腹血糖、机械痛阈值、热痛阈值、坐骨神经传导速度的变化；观察大鼠坐骨神经病理变化；检测大鼠坐骨神经中超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量；检测大鼠坐骨神经中HMGB1、RAGE蛋白表达水平和核因子κBp65（NF-κBp65）蛋白磷酸化水平。结果与对照组比较，DPN组大鼠坐骨神经病理损伤严重，空腹血糖、热痛阈值、MDA含量及HMGB1、RAGE蛋白表达水平和NF-κBp65蛋白磷酸化水平均显著升高（P＜0.05），机械痛阈值、感觉神经传导速度、运动神经传导速度、SOD活性显著降低/减慢（P＜0.05）；与DPN组比较，穿心莲内酯低、高剂量组和硫辛酸组大鼠上述指标均显著改善（P＜0.05），rHMGB1组对应指标变化趋势与上述3个给药组相反（P＜0.05）；并且，rHMGB1可减弱高剂量穿心莲内酯对DPN大鼠血糖的降低作用及坐骨神经氧化应激损伤的改善作用（P＜0.05）。结论穿心莲内酯可能通过抑制HMGB1/RAGE信号通路来降低血糖、抑制氧化应激，进而改善DPN大鼠坐骨神经损伤。 |
| ABSTRACT： | OBJECTIVE To investigate the impacts of andrographolide on sciatic nerve function injury in diabetic peripheral neuropathy （DPN） rats by regulating high-mobility group protein box 1 （HMGB1）/receptor for advanced glycation end products （RAGE） signal pathway. METHODS A total of 84 rats were randomly divided into the control group （normal saline）， DPN group （normal saline）， low-dose andrographolide group （0.833 mg/kg）， high-dose andrographolide group （3.332 mg/kg）， lipoic acid group （positive control， 0.1 g/kg）， recombinant rat HMGB1 protein （rHMGB1） group （8 μg/kg）， and high-dose andrographolide+ rHMGB1 group， with 12 rats in each group. All rats except those in the control group were fed with high glucose and high fat diet combined with intraperitoneal injections of streptozotocin to establish the DPN rat model. After 24 hours of successful modeling， medication was administered daily for 8 weeks. The changes in fasting blood glucose， mechanical pain threshold， heat pain threshold and sciatic nerve conduction velocity were detected. Pathological changes in the sciatic nerve of rats and the activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） in the sciatic nerve of rats were also detected. Besides， the expressions of HMGB1， RAGE proteins and phosphorylation level of nuclear factor κB p65（NF-κB p65） protein in rat sciatic nerves were found. RESULTS Compared with the control group， the pathological damage of the sciatic nerve of rats in the DPN group was strengthened， the fasting blood glucose， heat pain threshold， MDA content and the 诊治。E-mail：dqiaur@163.com expressions of HMGB1， RAGE proteins and phosphorylation level of NF-κB p65 protein were increased （P＜0.05）， while the mechanical pain threshold， sensory nerve conduction velocity， motor nerve conduction velocity， and SOD activity were decreased/slowed down （P＜0.05）. Compared with the DPN group， the above indexes were significantly potentiated in the andrographolide low- and high-dose groups and lipoic acid group （P＜0.05）， and the corresponding trends in the rHMGB1 group were opposite to those in the above three administration groups （P＜0.05）. Moreover， rHMGB1 attenuated the hypoglycemic effect of high-dose andrographolide on blood glucose and the improvement of oxidative stress injury in the sciatic nerve of DPN rats （P＜0.05）. CONCLUSIONS Andrographolide may reduce blood glucose by inhibiting the HMGB1/RAGE pathway and oxidative stress， thus ameliorating sciatic nerve injury in DPN rats. |
| 期刊： | 2024年第35卷第05期 |
| 作者： | 孙跃先；王九妹；崔新刚；于晶 |
| AUTHORS： | SUN Yuexian，WANG Jiumei，CUI Xingang，YU Jin |
| 关键字： | 穿心莲内酯；糖尿病周围神经病变；高迁移率族蛋白B1；晚期糖基化终产物受体；坐骨神经；氧化应激 |
| KEYWORDS： | andrographolide； diabetic peripheral neuropathy； high-mobility group protein box 1； receptor for advanced |
| 阅读数： | 29 次 |
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