| 张静,李妮.天丹通络胶囊调控 LKB1/AMPK信号通路对急性脑梗死神经炎症的作用机制研究[J].安徽医药,2025,29(6):1094-1100. |
| 天丹通络胶囊调控 LKB1/AMPK信号通路对急性脑梗死神经炎症的作用机制研究 |
| The mechanism of Tiandan Tongluo capsules in regulating the LKB1/AMPK signaling pathway on neuroinflammation in acute cerebral infarction |
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| DOI：10.3969/j.issn.1009-6469.2025.06.007 |
| 中文关键词: 脑梗死 天丹通络胶囊 LKB1/AMPK信号通路 神经炎症 细胞凋亡 |
| 英文关键词: Brain Infarction Tiandan Tongluo capsules LKB1/AMPK signaling pathway Neuroinflammation Apoptosis |
| 基金项目:陕西省医学科学研究课题计划项目( 2020JM4234) |
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| 中文摘要: |
| 目的探讨天丹通络胶囊( TD)调控肝激酶 B1(LKB1)/AMP活化的蛋白质激酶( AMPK)信号通路对急性脑梗死神经炎症的影响。方法 2022年 7月至 2023年 7月，将 48只 SD大鼠按照随机数字表法分为假手术组( sham组)、模型组( model组)、天丹通络胶囊低剂量组(TD-L组)、天丹通络胶囊高剂量组( TD-H组)每组各 12只。采用金属丝闭塞法建立大鼠脑梗死模型。术后第 7天进行动物行为学分析，观察天丹通络胶囊对细胞的病理及神，经保护作用。酶联免疫吸附试验( ELISA)检测炎症因子的表达。原位末端转移酶标记法( TUNEL)染色分析细胞凋亡。免疫组织化学和蛋白质印迹法分析 LKB1/AMPK信号通路活性。结果与 sham组相比， model组的 Zea-longa评分显著升高，而 TD-L组和 TD-H组的评分则明显低于 model组。 ELISA结果表显示， model组促炎因子白细胞介素( IL)-1β和肿瘤坏死因子 α(TNF-α)的水平显著升高，抗炎因子 IL-10的表达减少，而 TD-L组和 TD-H组 IL-1β和 TNF-α的水平显著降低，抗炎因子 IL-10的表达提高。此外， model组 TUNEL阳性细胞数量明显增加，而 TD-L组和 TD-H组的 TUNEL阳性细胞数量则明显少于 model组。 TD-L组和 TD-H组活化胱天蛋白酶 3(cleaved caspase-3)和活化胱天蛋白酶 9(cleaved caspase-9)表达相较于 model组显著降低。与 sham组 LKB1(37.5±3.2)、 AMPK(38.2±2.9)相比， model组 LKB1(24.6±3.7)和 AMPK(25.5±3.4)的相对蛋白表达水平显著降低。与 model组相比， TD-L组的 LKB1(46.9±4.7)、 AMPK(48.8±3.9)和 TD-H组的 LKB1(59.2±5.6)、 AMPK(61.3±6.1)水平显著升高。结论天丹通络胶囊可抑制脑梗死大鼠神经细胞凋亡，发挥保护作用，这可能与 LKB1/AMPK信号通路有关。 |
| 英文摘要: |
| Objective To investigate the effect of Tiandan Tongluo capsules (TD) on regulating the LKB1/AMPK signaling pathway and its impact on neuroinflammation in acute cerebral infarction.Methods From July 2022 to July 2023, 48 SD rats were randomly di-vided into four groups: sham group, model group, low-dose group of Tendan Tongluo capsule (TD-L group), and high-dose group of Ten-dan Tongluo capsule (TD-H group), with 12 rats per group. A cerebral infarction model was established using metal wire occlusion. Onpostoperative day 7, behavioural analysis was conducted to evaluate TD's pathological and neuroprotective effects. Enzyme-linked im-munosorbent assay (ELISA) measured inflammatory factors. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining assessed apoptosis, and immunohistochemistry and Western blotting analyzed LKB1/AMPK signalling pathway activ-ity.Results The Zea-Longa scores in the model group were significantly higher than those in the sham group. Conversely, the TD-L and TD-H groups showed significantly lower scores compared to the model group. ELISA results demonstrated that pro-inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were significantly elevated in the model group, while the anti-in-flammatory factor interleukin-10 (IL-10) was reduced. In contrast, the TD-L and TD-H groups exhibited significantly decreased levels of IL-1β and TNF-α and increased IL-10 expression. Additionally, the model group displayed a marked increase in TUNEL-positive cells, whereas the TD-L and TD-H groups showed significant reductions in TUNEL-positive cells relative to the model group. Further-more, cleaved caspase-3 and cleaved caspase-9 expression levels were considerably lower in the TD-L and TD-H groups compared tothe model group. The relative protein expression levels of LKB1 (24.6±3.7) and AMPK (25.5±3.4) in the model group were significantlylower than those in the sham group (LKB1: 37.5±3.2; AMPK: 38.2±2.9). Compared to the model group, the TD-L group exhibited signif-icantly higher LKB1 (46.9±4.7) and AMPK (48.8±3.9) levels, and the TD-H group showed even greater increases in LKB1 (59.2±5.6) and AMPK (61.3±6.1) expression.Conclusion Tiandan Tongluo capsules inhibit neuronal apoptosis in rats with cerebral infarctionand exert a neuroprotective role, potentially mediated through the LKB1/AMPK signaling pathway. |
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