目的 探讨黄芪甲苷调控脑源性神经生长因子（BDNF）-酪氨酸激酶受体B（TrkB）-磷脂酰肌醇-3-激酶（PI3K）-蛋白激酶B（Akt）信号通路改善大鼠糖尿病周围神经病变（DPN）的作用机制。方法 选用SPF级雄性SD大鼠，随机分为对照组、模型组、甲钴胺（0.25 mg·kg^-1）组以及黄芪甲苷高、中、低剂量（80、40、20 mg·kg^-1）组，除对照组外，采用高脂饲料联合ip链脲佐菌素（STZ）法诱导DPN大鼠模型，模型制备成功后，各给药组ig给药，对照组和模型组大鼠给予相同体积的0.9%氯化钠溶液，每天1次，连续给药8周。造模前、造模后、给药后监测各组大鼠空腹血糖（FBG）、热缩足反射潜伏期（TWL）；给药后，检测各组大鼠坐骨神经传导速度；TUNEL法分析大鼠背根神经节神经元凋亡水平；实时荧光定量PCR（qRT-PCR）和Western blotting法检测大鼠背根神经节中BDNF、TrkB、PI3K、Akt mRNA和蛋白表达水平。结果 与对照组相比，模型组大鼠FBG水平显著升高（P＜0.01），TWL水平明显下降（P＜0.01），坐骨神经传导速度明显减慢（P＜0.01），大鼠背根神经节BDNF、TrkB、PI3K、Akt mRNA和蛋白表达水平显著下调（P＜0.05、0.01），背根神经节神经元出现典型早期凋亡细胞（P＜0.01）。经药物干预后，与模型组相比，黄芪甲苷高、中剂量组FBG水平均明显下降（P＜0.05），TWL水平明显上升（P＜0.05），黄芪甲苷各剂量组坐骨神经传导速度显著提高（P＜0.05、0.01），黄芪甲苷各剂量组BDNF、TrkB、PI3K、AKT mRNA和蛋白表达水平显著上升（P＜0.05、0.01），大鼠背根神经节神经元凋亡水平降低显著（P＜0.05、0.01）。结论 黄芪甲苷可通过调控BDNF-TrkB-PI3K-Akt信号通路，减轻背根神经节神经元凋亡，改善大鼠DPN。

Objective To explore the mechanism of astragaloside IV in regulating the brain-derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB)-phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway to improve diabetic peripheral neuropathy (DPN) in rats.Methods SPF-grade male SD rats were randomly divided into the control group, model group, mecobalamin (0.25 mg·kg^-1) group, and astragaloside IV high-, medium-, and low-dose (80, 40, and 20 mg·kg^-1) groups. Except for the control group, the DPN rat model was induced by high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). After successful model establishment, each drug group was ig administered, and the control and model groups were given the same volume of 0.9% sodium chloride solution once a day for eight consecutive weeks. Fasting blood glucose (FBG) and thermal withdrawal latency (TWL) of each group were monitored before modeling, after modeling, and after drug administration. After drug administration, the sciatic nerve conduction velocity of each group was detected. The apoptosis level of dorsal root ganglion neurons was analyzed by TUNEL method. The mRNA and protein expression levels of BDNF, TrkB, PI3K, and Akt in the dorsal root ganglion were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting.Results Compared with the control group, the FBG level of the model group was significantly increased (P<0.01), the TWL level was significantly decreased (P<0.01), and the sciatic nerve conduction velocity was significantly slowed down (P<0.01). The mRNA and protein expression levels of BDNF, TrkB, PI3K, and Akt in the dorsal root ganglion were significantly down-regulated (P<0.05, 0.01), and typical early apoptotic cells appeared in the dorsal root ganglion neurons (P<0.01). After drug intervention, compared with the model group, the FBG levels of the astragaloside IV high-and medium-dose groups were significantly decreased (P<0.05), the TWL levels were significantly increased (P<0.05), the sciatic nerve conduction velocity of each astragaloside IV dose group was significantly improved (P<0.05, 0.01), the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in each astragaloside IV dose group were significantly increased (P<0.05, 0.01), and the apoptosis level of dorsal root ganglion neurons was significantly decreased (P<0.05, 0.01).Conclusion Astragaloside IV can improve DPN in rats by regulating the BDNF-TrkB-PI3K-Akt signaling pathway, reducing the apoptosis of dorsal root ganglion neurons.

R285.5

江苏省卫生健康委科研项目（Z2020054）；江苏高校“青蓝工程”资助项目（苏教师函［2023］27号）；江苏省高职院校教师访学研修项目（2024GRFX067）