温通活血乳膏通过抑制mTOR/4E-BP1通路改善糖尿病周围神经病变

doi:10.11958/20253618

天津医药 ›› 2026, Vol. 54 ›› Issue (8): 796-801.doi: 10.11958/20253618

温通活血乳膏通过抑制mTOR/4E-BP1通路改善糖尿病周围神经病变

阿曼古丽·苏力唐¹(), 铁玲², 马静¹, 马丽¹^,^△()

¹ 新疆维吾尔自治区中医医院内分泌科（邮编830000）
² 新疆维吾尔自治区中医医院耳鼻喉科（邮编830000）

收稿日期:2025-12-12 修回日期:2026-04-02 出版日期:2026-08-15 发布日期:2026-08-07
通讯作者: △E-mail：malixj322122@163.com
作者简介:阿曼古丽·苏力唐（1982），女，副主任医师，主要从事糖尿病周围神经病变方面研究。E-mail：aman1165@163.com
基金资助:
新疆维吾尔自治区自然科学基金面上项目(2022D01C174)

Wentong Huoxue Cream alleviating diabetic peripheral neuropathy by inhibiting the mTOR/4E-BP1 pathway

AMANGULI Sulitang¹(), TIE Ling², MA Jing¹, MA Li¹^,^△()

¹ Department of Endocrinology, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi 830000, China
² Department of Otorhinolaryngology, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi 830000, China

Received:2025-12-12 Revised:2026-04-02 Published:2026-08-15 Online:2026-08-07
Contact: △E-mail： malixj322122@163.com

阿曼古丽·苏力唐, 铁玲, 马静, 马丽. 温通活血乳膏通过抑制mTOR/4E-BP1通路改善糖尿病周围神经病变[J]. 天津医药, 2026, 54(8): 796-801.

AMANGULI Sulitang, TIE Ling, MA Jing, MA Li. Wentong Huoxue Cream alleviating diabetic peripheral neuropathy by inhibiting the mTOR/4E-BP1 pathway[J]. Tianjin Medical Journal, 2026, 54(8): 796-801.

摘要/Abstract

摘要：

目的探讨温通活血乳膏是否通过调控哺乳动物雷帕霉素靶蛋白（mTOR）/真核翻译起始因子4E结合蛋白1（4E-BP1）信号通路影响雪旺细胞（SC），从而减轻糖尿病周围神经病变（DPN）模型大鼠的坐骨神经损伤。方法将60只8周龄雄性SD大鼠随机分为正常组（10只）与造模组（50只）。造模组采用链脲佐菌素腹腔注射联合高糖高脂饲料喂养建立DPN模型。将成模大鼠随机分为5组：模型组、温通活血乳膏高剂量组、温通活血乳膏低剂量组、基质组（空白乳膏）及二甲双胍组（阳性对照）。连续干预4周后，检测大鼠热甩尾潜伏期；采用HE染色观察坐骨神经病理形态；透射电镜观察髓鞘超微结构及SC自噬体；通过Western blot检测坐骨神经中mTOR、磷酸化mTOR（p-mTOR）、4E-BP1、磷酸化4E-BP1（p-4E-BP1）蛋白表达及微管相关蛋白1轻链3（LC3-Ⅱ）水平；采用实时荧光定量PCR检测mTOR、4E-BP1和LC3-Ⅱ的mRNA表达。结果与模型组相比，温通活血乳膏各剂量组热甩尾潜伏期明显缩短（P<0.05），神经病理损伤及超微结构破坏明显减轻，SC中自噬体数量减少。Western blot和PCR结果显示，温通活血乳膏各剂量组p-mTOR、mTOR、p-4E-BP1、4E-BP1及LC3-Ⅱ蛋白或mRNA表达水平均较模型组降低（P<0.05），且高剂量组改善效果较低剂量组显著。结论温通活血乳膏能显著改善DPN大鼠的神经痛觉过敏和髓鞘病理损伤，其机制可能与抑制mTOR/4E-BP1信号通路过度激活，并下调自噬相关蛋白LC3-Ⅱ水平有关。

关键词: 糖尿病神经病变, TOR丝氨酸-苏氨酸激酶, 真核细胞起始因子4E, 许旺细胞, 坐骨神经, 自噬, 温通活血乳膏

Abstract:

Objective To investigate whether the Wentong Huoxue Cream affected Schwann cells (SC) by regulating the mammalian target of rapamycin (mTOR)/eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) signaling pathway, thereby alleviating sciatic nerve injury in diabetic peripheral neuropathy (DPN) model rats. Methods Sixty 8-week-old male SD rats were randomly divided into the normal group (10 rats) and the model group (50 rats). The model group was established by intraperitoneal injection of streptozotocin (STZ) combined with high-sugar and high-fat diet. The rats in the model group were randomly divided into 5 groups: the model group, the high-dose Wentong Huoxue Cream group, the low-dose Wentong Huoxue Cream group, the matrix group (blank cream) and the metformin group (positive control). After 4 weeks of continuous intervention, the latency of hot tail flicking of rats was detected. The pathological morphology of the sciatic nerve was observed by HE staining. The ultrastructure of myelin sheath and autophagosomes of Schwann cells were observed by transmission electron microscopy. The protein expression levels of mTOR, phosphorylated mTOR (p-mTOR), 4E-BP1, phosphorylated 4E-BP1 (p-4E-BP1) and microtubule-associated protein 1 light chain 3 (LC3-Ⅱ) in sciatic nerve were detected by Western blot assay. The mRNA expressions of mTOR, 4E-BP1 and LC3-Ⅱwere detected by real-time fluorescence quantitative PCR. Results Compared with the model group, the latency of tail flicking was significantly shortened in the Wentong Huoxue Cream groups (P<0.05), the nerve pathological damage and ultrastructural destruction were significantly alleviated and the number of autophagosomes in Schwann cells decreased. Western blot assay and PCR results showed that the protein or mRNA expression levels of p-mTOR, mTOR, p-4E-BP1, 4E-BP1 and LC3-Ⅱwere lower in the Wentong Huoxue Cream groups than those in the model group (P<0.05), and the improvement effect was more significant in the high-dose Wentong Huoxue Cream group than that of the low-dose Wentong Huoxue Cream group. Conclusion Wentong Huoxue Cream can significantly improve neuropathic hyperalgesia and myelin pathological damage in DPN rats. The mechanism may be related to the inhibition of excessive activation of the mTOR/4E-BP1 signaling pathway and the down-regulation of autophagy-related protein LC3-Ⅱ level.

Key words: diabetic neuropathies, TOR serine-threonine kinases, eukaryotic initiation factor-4E, Schwann cells, sciatic nerve, autophagy, Wentong Huoxue Cream

中图分类号:

R587.25

图/表 7

参考文献 18

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基因名称	引物序列（5′→3′）	产物大小/bp
mTOR	上游：GTGTGGCAAGAGCGGCAGAC 下游：TGTTGGCAGAGGATGGTCAAGTTG	97
4E-BP1	上游：CCCAAAGGACCTGCCAACCATTC 下游：CACCACCTGCCCGCTTATCTTC	116
LC3-Ⅱ	上游：CCAGGACAAGCAGGCAGATGAAG 下游：CAGGCTTTCGTCTCTTCCACCATC	149
β-actin	上游：CCCATCTATGAGGGTTACGC 下游：TTTAAATGTCACGCACGATTTC	151

基因名称	引物序列（5′→3′）	产物大小/bp
mTOR	上游：GTGTGGCAAGAGCGGCAGAC 下游：TGTTGGCAGAGGATGGTCAAGTTG	97
4E-BP1	上游：CCCAAAGGACCTGCCAACCATTC 下游：CACCACCTGCCCGCTTATCTTC	116
LC3-Ⅱ	上游：CCAGGACAAGCAGGCAGATGAAG 下游：CAGGCTTTCGTCTCTTCCACCATC	149
β-actin	上游：CCCATCTATGAGGGTTACGC 下游：TTTAAATGTCACGCACGATTTC	151

组别	血糖/（mmol/L）		体质量/g		热甩尾潜伏期/s
组别	治疗前	治疗后	治疗前	治疗后	热甩尾潜伏期/s
正常组	5.20±0.27	5.55±0.40	506.84±39.50	584.61±32.58	3.98±1.15
模型组	29.85±2.69^a	31.30±1.10^a	374.04±65.64^a	363.96±37.92^a	9.16±2.22^a
低剂量组	30.95±2.97^a	28.35±1.87^a	388.58±42.77^a	358.80±51.64^a	7.14±2.40^ab
高剂量组	29.85±2.07^a	31.61±1.60^a	375.33±57.35^a	347.40±51.54^a	5.02±1.49^abc
基质组	28.25±1.87^a	33.32±1.77^a	374.04±65.64^a	363.96±37.92^a	10.15±3.23^a
二甲双胍组	28.25±2.60^a	7.05±0.90^b	399.56±56.03^a	378.60±44.97^a	6.41±1.66^ab
F	75.130^＊＊	106.876^＊＊	202.301^＊＊	198.103^＊＊	167.504^＊＊

组别	血糖/（mmol/L）		体质量/g		热甩尾潜伏期/s
组别	治疗前	治疗后	治疗前	治疗后	热甩尾潜伏期/s
正常组	5.20±0.27	5.55±0.40	506.84±39.50	584.61±32.58	3.98±1.15
模型组	29.85±2.69^a	31.30±1.10^a	374.04±65.64^a	363.96±37.92^a	9.16±2.22^a
低剂量组	30.95±2.97^a	28.35±1.87^a	388.58±42.77^a	358.80±51.64^a	7.14±2.40^ab
高剂量组	29.85±2.07^a	31.61±1.60^a	375.33±57.35^a	347.40±51.54^a	5.02±1.49^abc
基质组	28.25±1.87^a	33.32±1.77^a	374.04±65.64^a	363.96±37.92^a	10.15±3.23^a
二甲双胍组	28.25±2.60^a	7.05±0.90^b	399.56±56.03^a	378.60±44.97^a	6.41±1.66^ab
F	75.130^＊＊	106.876^＊＊	202.301^＊＊	198.103^＊＊	167.504^＊＊

组别		mTOR		p-mTOR
正常组		0.46±0.02		1.32±0.09
模型组		0.54±0.03^a		2.44±0.32^a
低剂量组		0.45±0.04^b		1.36±0.08^b
高剂量组		0.29±0.04^bc		1.13±0.04^bc
基质组		0.27±0.04^b		1.17±0.24^b
二甲双胍组		0.42±0.06^b		1.27±0.09^b
F		72.265^＊＊		82.863^＊＊
组别	4E-BP1		p-4E-BP1		LC3-Ⅱ
正常组	0.53±0.09		0.12±0.02		0.42±0.04
模型组	1.27±0.17^a		1.29±0.17^a		1.27±0.21^a
低剂量组	0.31±0.05^b		1.17±0.13^b		0.99±0.24^b
高剂量组	1.16±0.13^bc		0.31±0.05^bc		0.56±0.11^bc
基质组	0.41±0.08^b		0.40±0.08^b		0.43±0.10^b
二甲双胍组	0.12±0.02^b		0.53±0.09^b		0.64±0.09^b
F	219.903^＊＊		233.692^＊＊		54.592^＊＊

温通活血乳膏通过抑制mTOR/4E-BP1通路改善糖尿病周围神经病变

Wentong Huoxue Cream alleviating diabetic peripheral neuropathy by inhibiting the mTOR/4E-BP1 pathway

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组别	mTOR	4E-BP1	LC3-Ⅱ
正常组	1.00±0.15	1.08±0.13	1.02±0.24
模型组	3.15±0.85^a	1.98±0.40^a	2.35±0.33^a
低剂量组	2.23±1.15^b	1.60±0.70^b	2.25±0.26^b
高剂量组	1.63±0.80^bc	1.08±0.24^bc	1.52±0.30^bc
基质组	3.62±0.76	1.80±0.22^b	2.54±0.50
二甲双胍组	2.34±0.69^b	1.48±0.53^b	1.71±0.22^b
F	219.705^＊＊	77.165^＊＊	124.971^＊＊

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