| 引用本文: |
马静, 阿曼古丽·苏力唐, 藏登, 李惠, 徐利娟, 铁玲, 王冲, 王先敏, 马丽.温通活血乳膏调控PERK-eIF2α通路介导内质网应激改善糖尿病周围神经病变的研究[J].湖南中医药大学学报,2026,46(3):464-471[点击复制] |
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| 温通活血乳膏调控PERK-eIF2α通路介导内质网应激改善糖尿病周围神经病变的研究 |
| 马静,阿曼古丽·苏力唐,藏登,李惠,徐利娟,铁玲,王冲,王先敏,马丽 |
| (新疆医科大学第四临床医学院, 新疆 乌鲁木齐市 830099;新疆维吾尔自治区中医医院, 新疆 乌鲁木齐市 830099) |
| 摘要: |
| 目的 本研究旨在探讨温通活血乳膏对糖尿病周围神经病变（DPN）大鼠坐骨神经内质网应激信号通路的影响，以揭示该药物在改善糖尿病引起的周围神经病变中的潜在作用机制。方法 研究取60只SD大鼠，采用随机数字表法，随机挑选10只大鼠设为空白组，给予基础饲料。其余大鼠给予高糖高脂饲料6周，给予链脲佐菌素腹腔注射建立糖尿病模型，成模后继续给予高糖高脂饮食8周，当双下肢坐骨神经的感觉或运动传导速度减缓超过11 %，则判定为DPN大鼠模型。将大鼠随机分为5组：模型组，模型+空白乳膏组，模型+温通活血乳膏低剂量组（WTHX低剂量组），模型+温通活血乳膏中剂量组（WTHX中剂量组），模型+温通活血乳膏高剂量组（WTHX高剂量组），每组10只，中药干预4周。本次实验观测各组大鼠一般情况，检测治疗前后血糖水平；治疗结束后，进行热甩尾实验；并采用光镜观察坐骨神经病理变化，电镜观察坐骨神经、腓肠肌的超微结构变化；Western bolt检测坐骨神经中磷酸化蛋白激酶R样内质网激酶（p-PERK）、PERK、磷酸化真核翻译起始因子2α激酶（p-elF2α）、elF2α、活化转录因子4（ATF4）、C/EBP同源蛋白（CHOP）、胱天蛋白酶3（Caspase-3）蛋白表达水平；TUNEL法检测坐骨神经细胞凋亡情况。结果 与空白组相比，模型组对热度敏感性降低、潜伏期延长（P<0.001）；坐骨神经及腓肠肌病理变化和超微结构发生明显改变；p-PERK、p-elF2α、ATF4、CHOP、Caspase-3蛋白的表达水平均过表达（P<0.001）。与模型组相比，WTHX低、中、高剂量组热甩尾时间缩短（P<0.01），并有效改善坐骨神经及腓肠肌病理损伤与超微结构紊乱。WTHX高剂量组可显著下调坐骨神经中 p-PERK、p-elF2α、ATF4、CHOP、Caspase-3 蛋白表达水平（P<0.01），减轻内质网应激水平。结论 温通活血乳膏通过调控PERK/eIF2α/ATF4/CHOP通路抑制内质网应激相关凋亡，进而发挥对DPN神经与肌肉的双重保护作用。 |
| 关键词: 糖尿病周围神经病变 温通活血乳膏 内质网应激 细胞凋亡 PERK/elF2α/ATF4/CHOP通路 |
| DOI：10.3969/j.issn.1674-070X.2026.03.005 |
| 投稿时间：2025-10-23 |
| 基金项目:新疆维吾尔自治区重点研发项目（2023B03002-3）；新疆医科大学附属中医医院重点项目（ZYY2023ZD3）。 |
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| Wentong Huoxue Ointment ameliorates diabetic peripheral neuropathy by regulating PERK-eIF2α pathway-mediated endoplasmic reticulum stress |
| MA Jing, Amanguli Suletang, ZANG Deng, LI Hui, XU Lijuan, TIE Ling, WANG Chong, WANG Xianmin, MA Li |
| (The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang 830099, China;Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, Xinjiang 830099, China) |
| Abstract: |
| Objective To investigate the effects of Wentong Huoxue (WTHX) Ointment on the endoplasmic reticulum stress signaling pathway in the sciatic nerve of rats with diabetic peripheral neuropathy (DPN), and to explore its potential mechanism of action in alleviating diabetes-induced peripheral neuropathy. Methods Sixty SD rats were used in the study, and 10 rats were randomly selected as the blank group and given basic diet by using the random number table method.The other rats were given high sugar and high-fat diet for 6 weeks, and streptozotocin was injected intraperitoneally to establish the diabetes model. After the model was established, the rats were given high sugar and high-fat diet for 8 weeks. When the sensory or motor conduction velocity of sciatic nerve in both lower limbs slowed down by more than 11%, it was judged as the DPN rat model. DPN rats were randomly divided into five groups: model group, model + blank cream group, model + Wentong Huoxue cream low-dose group (WTHX low-dose group), model + Wentong Huoxue cream medium dose group (WTHX medium dose group), model + Wentong Huoxue cream high-dose group (WTHX high-dose group), 10 rats in each group, with drug intervention for 4 weeks. In this experiment, the general conditions of rats in each group were observed, and blood glucose levels were measured before and after treatment. After treatment completion, the hot plate tail-flick test was performed. Pathological changes in the sciatic nerve were observed under light microscopy, and ultrastructural changes in the sciatic nerve and gastrocnemius muscle were examined under electron microscopy. The protein expression levels of p-PERK, PERK, p-eIF2α, eIF2α, ATF4, CHOP, and Caspase-3 in the sciatic nerve were detected by Western blot. Cell apoptosis in the sciatic nerve was assessed using the TUNEL method. Results Compared with the blank group, the model group showed reduced thermal sensitivity and prolonged tail-flick latency (P<0.001). Significant pathological and ultrastructural changes were observed in the sciatic nerve and gastrocnemius muscle. The expression levels of p-PERK, p-eIF2α, ATF4, CHOP, and Caspase-3 proteins were significantly upregulated (P<0.001). Compared with the model group, the low-, medium-, and high-dose WTHX groups exhibited shortened tail-flick latency (P<0.01) and significantly ameliorated pathological damage and ultrastructural disorders in the sciatic nerve and gastrocnemius muscle. The high-dose WTHX group significantly downregulated the expression levels of p-PERK, p-eIF2α, ATF4, CHOP, and Caspase-3 proteins in the sciatic nerve (P<0.01), thereby alleviating endoplasmic reticulum stress. Conclusion WTHX Ointment exerts dual protective effects on nerves and muscles in DPN by regulating the PERK/eIF2α/ATF4/CHOP pathway to inhibit endoplasmic reticulum stress-related apoptosis. |
| Key words: diabetic peripheral neuropathy Wentong Huoxue Ointment endoplasmic reticulum stress apoptosis PERK/eIF2α/ATF4/CHOP pathway |
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