目的 探討黃芪甲苷調(diào)控腦源性神經(jīng)生長因子（BDNF）-酪氨酸激酶受體B（TrkB）-磷脂酰肌醇-3-激酶（PI3K）-蛋白激酶B（Akt）信號通路改善大鼠糖尿病周圍神經(jīng)病變（DPN）的作用機制。方法 選用SPF級雄性SD大鼠，隨機分為對照組、模型組、甲鈷胺（0.25 mg·kg^-1）組以及黃芪甲苷高、中、低劑量（80、40、20 mg·kg^-1）組，除對照組外，采用高脂飼料聯(lián)合ip鏈脲佐菌素（STZ）法誘導(dǎo)DPN大鼠模型，模型制備成功后，各給藥組ig給藥，對照組和模型組大鼠給予相同體積的0.9%氯化鈉溶液，每天1次，連續(xù)給藥8周。造模前、造模后、給藥后監(jiān)測各組大鼠空腹血糖（FBG）、熱縮足反射潛伏期（TWL）；給藥后，檢測各組大鼠坐骨神經(jīng)傳導(dǎo)速度；TUNEL法分析大鼠背根神經(jīng)節(jié)神經(jīng)元凋亡水平；實時熒光定量PCR（qRT-PCR）和Western blotting法檢測大鼠背根神經(jīng)節(jié)中BDNF、TrkB、PI3K、Akt mRNA和蛋白表達水平。結(jié)果 與對照組相比，模型組大鼠FBG水平顯著升高（P＜0.01），TWL水平明顯下降（P＜0.01），坐骨神經(jīng)傳導(dǎo)速度明顯減慢（P＜0.01），大鼠背根神經(jīng)節(jié)BDNF、TrkB、PI3K、Akt mRNA和蛋白表達水平顯著下調(diào)（P＜0.05、0.01），背根神經(jīng)節(jié)神經(jīng)元出現(xiàn)典型早期凋亡細胞（P＜0.01）。經(jīng)藥物干預(yù)后，與模型組相比，黃芪甲苷高、中劑量組FBG水平均明顯下降（P＜0.05），TWL水平明顯上升（P＜0.05），黃芪甲苷各劑量組坐骨神經(jīng)傳導(dǎo)速度顯著提高（P＜0.05、0.01），黃芪甲苷各劑量組BDNF、TrkB、PI3K、AKT mRNA和蛋白表達水平顯著上升（P＜0.05、0.01），大鼠背根神經(jīng)節(jié)神經(jīng)元凋亡水平降低顯著（P＜0.05、0.01）。結(jié)論 黃芪甲苷可通過調(diào)控BDNF-TrkB-PI3K-Akt信號通路，減輕背根神經(jīng)節(jié)神經(jīng)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

江蘇省衛(wèi)生健康委科研項目（Z2020054）；江蘇高?！扒嗨{工程”資助項目（蘇教師函［2023］27號）；江蘇省高職院校教師訪學(xué)研修項目（2024GRFX067）