| 许永杰,贾晓龙,王燕领.茯苓酸调节 cAMP/PKA/CREB信号通路对脑出血大鼠脑组织损伤的影响[J].安徽医药,2025,29(5):898-902. |
| 茯苓酸调节 cAMP/PKA/CREB信号通路对脑出血大鼠脑组织损伤的影响 |
| Effect of pachymenic acid on brain tissue damage in rats with cerebral hemorrhage by regulating the cAMP/PKA/CREB signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2025.05.009 |
| 中文关键词: 茯苓属 cAMP/PKA/CREB信号通路 脑出血 |
| 英文关键词: Wolfiporia cAMP/PKA/CREB signaling pathway Cerebral hemorrhage |
| 基金项目:河北省卫生健康委基金项目( 20210215) |
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| 中文摘要: |
| 目的探究茯苓酸对脑出血大鼠脑组织损伤的影响及其可能作用机制。方法 2023年 1―5月将大鼠按随机数字表法分为假手术组、模型组、茯苓酸低、高剂量组和茯苓酸高剂量 +H-89(cAMP抑制剂)组，每组 10只。采用 Zea-Longa评分法评估各组大鼠神经功能；酶联免疫吸附法检测血清白细胞介素 1β(IL-1β)白细胞介素 10(IL-10)、肿瘤坏死因子 α(TNF-α)、环磷酸腺苷( cAMP)水平；苏木精 -伊红( HE)染色观察海马神经元损伤；脱氧核、糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)染色检测海马神经元凋亡；检测 B细胞淋巴瘤( Bcl-2)、 Bcl-2相关 X蛋白( Bax)、 cAMP/蛋白激酶 A(PKA)/环磷酸腺苷反应元件结合蛋白( CREB)通路蛋白表达。结果与假手术组相比，模型组大鼠海马神经元结构严重损伤，神经功能评分( 2.80±0.37)分比( 0.10±0.02)分、 IL-1β(342.58±29.73)ng/L比( 30.67±2.84)ng/L、TNF-α(253.70±23.49)ng/L比( 14.38±1.26)ng/L水平、神经元凋亡率( 26.58±2.26)%比( 3.37±0.42)%、Bax蛋白表达( 0.91±0.08比 0.36±0.03)升高， IL-10(42.76±4.04)ng/L比( 178.93±16.63) ng/L、cAMP(1.42±0.13)μg/L比( 2.86±0.27)μg/L水平、 Bcl-2(0.28±0.02比 0.78±0.06)、 p-PKA/PKA(0.51±0.04比 1.16±0.11)、 CREB/p-CREB(0.32±0.03比 0.87±0.07)蛋白表达水平降低( P<0.05)；与模型组相比，茯苓酸低、高剂量组大鼠海马神经元损伤减轻，神经功能评分、 IL-1β、TNF-α水平、神经元凋亡率、 Bax蛋白表达降低， IL-10、cAMP水平、 Bcl-2、p-PKA/PKA、CREB/ p-CREB蛋白表达水平升高( P<0.05)； cAMP抑制剂 H-89可部分逆转茯苓酸对脑出血大鼠的改善作用( P<0.05)。结论茯苓酸可减轻脑出血大鼠脑组织损伤和炎症反应，可能与激活 cAMP/PKA/CREB信号通路有关。 |
| 英文摘要: |
| Objective To investigate the effect of pachymaric acid on brain tissue injury in rats with cerebral hemorrhage and its pos-sible mechanism.Methods From January to May 2023, SD rats were separated into sham surgery group, model group, low-dose pachy-menate group, high-dose pachymenate group, and high-dose pachymenate+H-89 (cAMP inhibitor) group according to random numbertable method. The neurological function of rats in each group was evaluated by Zea Longa scoring; enzyme linked immunosorbent assay(ELISA) was applied to detect serum levels of interleukin-1β (IL-1β), interleukin-10 (IL-10), tumor necrosis factor α (TNF-α), and cy-clic adenosine phosphate (cAMP); hematoxylin-eosin (HE) staining was applied to observe hippocampal neuronal damage; deoxyribonu-cleotide end transferase mediated notch end labeling (TUNEL) staining was applied to detect hippocampal neuronal apoptosis; the ex-pression of B-cell lymphoma (Bcl-2), Bcl-2 associated X protein (Bax), cAMP/ protein kinase A (PKA)/cyclic adenosine phosphate reac-tion element binding protein (CREB) pathway protein was detected.Results Compared with the sham surgery group, the hippocampalneuronal structure of rats in the model group was severely damaged, the neurological function score (2.80±0.37) points vs. (0.10±0.02) points, levels of IL-1β (342.58±29.73) ng/L vs. (30.67±2.84) ng/L and TNF-α (253.70±23.49) ng/L vs. (14.38±1.26) ng/L, neuronal apoptosis rate (26.58±2.26)% vs. (3.37±0.42)%, and the protein expression of Bax (0.91±0.08 vs. 0.36±0.03) were obviously increased, the levels of IL-10 (42.76±4.04) ng/L vs. (178.93±16.63) ng/L and cAMP (1.42±0.13) μg/L vs. (2.86±0.27) μg/L, the protein expression of Bcl-2 (0.28±0.02 vs. 0.78±0.06), p-PKA/PKA (0.51±0.04 vs. 1.16±0.11), and CREB/p-CREB (0.32±0.03 vs. 0.87±0.07) were obvi-ously reduced (P<0.05); compared with the model group, the structural damage of hippocampal neurons in the low and high dose Poricacid groups was obviously reduced, the neurological function score, levels of IL-1β and TNF-α, neuronal apoptosis rate, and the protein expression of Bax were obviously reduced, the levels of IL-10 and cAMP, the protein expression of Bcl-2, p-PKA/PKA, and CREB/p-CREB were obviously increased (P<0.05); cAMP inhibitor H-89 was able to partially reverse the improvement effect of poric acid on ce-rebral hemorrhage in rats (P<0.05).Conclusion Pachymaric acid can reduce brain tissue injury and inflammation in rats with cere-bral hemorrhage, which may be related to the activation of cAMP/PKA/CREB signaling pathway. |
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