| 张金峰,鲍莎莎,张晨星,鲍 备,耿文婧.苏合香丸调节cAMP-PKA信号通路对急性期脑梗死大鼠神经炎症和神经元凋亡的影响[J].现代生物医学进展英文版,2024,(12):2237-2243. |
| 苏合香丸调节cAMP-PKA信号通路对急性期脑梗死大鼠神经炎症和神经元凋亡的影响 |
| Effect of Suhexiang Pill on Regulation the cAMP-PKA Signal Pathway on Neuroinflammation and Neuron Apoptosis in Rats with Acute Cerebral Infarction |
| Received:December 06, 2023 Revised:December 30, 2023 |
| DOI：10.13241/j.cnki.pmb.2024.12.006 |
| 中文关键词: 苏合香丸 cAMP-PKA信号通路 急性期脑梗死 神经炎症 神经元凋亡 |
| 英文关键词: Suhexiang Pill cAMP-PKA signal pathway Acute cerebral infarction Neuroinflammation Neuronal apoptosis |
| 基金项目:河北省中医药管理局科研计划项目（2023380） |
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| 中文摘要: |
| 摘要 目的：探讨苏合香丸调节环磷酸腺苷(cAMP)/蛋白激酶A(PKA)信号通路对急性期脑梗死大鼠神经炎症和神经元凋亡的影响。方法：将SD大鼠分为模型组、假手术组、苏合香丸低剂量组（2.5 mL/kg）、苏合香丸中剂量组（5 mL/kg）、苏合香丸高剂量组（10 mL/kg）、尼莫地平组（2 mg/kg）、SQ22536（cAMP抑制剂）组（2.13 mg/kg）、苏合香丸高剂量+SQ22536组（10 mL/kg+2.13 mg/kg），每组24只。除假手术组大鼠仅分离动脉，其它组大鼠均需构建急性期脑梗死模型。建模成功后，进行给药处理，给药一天一次，持续2周。Zea-Longa评分法检测神经功能；干湿重法检测大鼠脑组织含水量；2,3,5-三苯基四唑氯化物（TTC）染色测定脑梗死体积；酶联免疫吸附测定法（ELISA）检测大鼠脑组织中肿瘤坏死因子-α（TNF-α）、白细胞介素 ( IL) -6、IL-1β、cAMP水平；苏木素-伊红（HE）染色检测大鼠神经元病理变化；TUNEL染色检测神经元凋亡；蛋白质印迹（western blot）检测大鼠脑组织中裂解的天冬氨酸特异性半胱氨酸蛋白酶-3（Cleaved Caspase-3）、Bcl-2相关X蛋白（Bax）、p-PKA蛋白表达。结果：与假手术组比较，模型组大鼠神经功能评分、神经元凋亡率、TNF-α、IL-1β、IL-6水平、脑梗死体积、Bax、Cleaved Caspase-3蛋白表达、脑组织含水量升高，cAMP、p-PKA蛋白表达降低（P<0.05），脑组织海马CA1区病理损伤严重。与模型组比较，苏合香丸低剂量组、苏合香丸中剂量组、苏合香丸高剂量组、尼莫地平组大鼠神经功能评分、TNF-α、IL-1β、IL-6水平、脑组织含水量、神经元凋亡率、脑梗死体积、Bax、Cleaved Caspase-3蛋白表达降低，cAMP、p-PKA蛋白表达升高（P<0.05），脑组织海马CA1区病理损伤减轻，SQ22536组对应指标变化趋势与上述相反（P<0.05）；SQ22536减弱了高剂量苏合香丸对急性期脑梗死大鼠神经炎症及神经元凋亡的抑制作用。结论：苏合香丸可能通过激活cAMP/PKA通路抑制急性期脑梗死大鼠神经炎症及神经元凋亡。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of Suhexiang Pill on regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway on neuroinflammation and neuronal apoptosis in rats with acute cerebral infarction. Methods: SD rats were divided into model group, sham surgery group, low-dose Suhexiang pill group (2.5 mL/kg), medium dose Suhexiang pill group (5 mL/kg), high-dose Suhexiang pill group (10 mL/kg), nimodipine group (2 mg/kg), SQ22536 (cAMP inhibitor) group (2.13 mg/kg), and high-dose Suhexiang pill+SQ22536 group (10 mL/kg+2.13 mg/kg), with 24 rats in each group. Except for the sham operated group where only the arteries were isolated, all other groups of rats were required to construct acute cerebral infarction models. After successful modeling, medication treatment was performed once a day for 2 weeks. Zea Longa scoring method was used to detect neural function; Dry wet weight method was used to detect the water content of rat brain tissue; Measure the volume of cerebral infarction with 2,3,5-triphenyltetrazole chloride (TTC) staining; Enzyme-linked immunosorbent assay (ELISA) was used to detect tumor necrosis factor-α (TNF-α), Interleukin(IL)-6, IL-1β, CAMP level in rat brain tissue; Hematoxylin eosin (HE) staining was used to detect pathological changes in rat neurons; TUNEL staining was used to detect neuronal apoptosis; Western blot was used to detect the expression of cleaved aspartate specific cysteine protease-3 (Cleaved Caspase-3), Bcl-2 related X protein (Bax), and p-PKA protein in rat brain tissue. Results: Compared with the sham surgery group, neurological function score, neuronal apoptosis rate, TNF-α, IL-1β, IL-6 levels, cerebral infarction volume, Bax, Cleaved Caspase-3 protein expression, and brain tissue water content increased in model group, the expression of cAMP and p-PKA proteins was reduced (P<0.05), and the pathological damage to the CA1 region of the hippocampus in brain tissue was severe. Compared with the model group, the low-dose Suhexiang pill group, medium dose Suhexiang pill group, high-dose Suhexiang pill group, nimodipine group of rat neurological function score, TNF-α, IL-1β, IL-6 level, brain tissue water content, neuronal apoptosis rate, cerebral infarction volume, Bax, Cleaved Caspase-3 protein expression decreased, CAMP and p-PKA protein expression increased (P<0.05), alleviation of pathological damage in hippocampal CA1 region of brain tissue, the trend of changes in corresponding indicators in the SQ22536 group was opposite to the above(P<0.05); SQ22536 weakened the inhibitory effect of high-dose Suhexiang Pill on neuroinflammation and neuronal apoptosis in rats with acute cerebral infarction. Conclusion: Suhexiang Pill may inhibit neuroinflammation and neuronal apoptosis in rats with acute cerebral infarction by activating the cAMP/PKA pathway. |
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