目的 探讨复方高滋斑片对脑缺血再灌注损伤的保护及可能机制。方法 将72只雄性SD大鼠随机分为假手术组、模型组及复方高滋斑片低、中、高剂量（135、270、540 mg/kg）组和阿托伐他汀钙片组，每组12只。采用大脑中动脉栓塞建立大鼠脑缺血再灌注损伤模型；造模后分析各组大鼠生存情况、体质量和Zea Longa评分，苏木精–伊红（HE）染色检测脑组织形态变化，TUNEL染色分析脑组织细胞凋亡情况，ELISA检测血清中炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和IL-1β及氧化应激指标丙二醛（MDA）和超氧化物歧化物酶（SOD）；通过转录组测序预测复方高滋斑片对脑缺血再灌注损伤保护作用的相关信号通路，并利用RT-PCR检测信号通路相关基因的表达。采用Western blotting检测缺血半暗带磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）相关蛋白和B淋巴细胞瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）和半胱氨酸天冬氨酸特异性蛋白酶-3（Caspase-3）凋亡相关蛋白。结果 与模型组相比，复方高滋斑片可以升高大鼠生存率和体质量，降低Zea Longa评分（P＜0.01）；促进脑组织形态恢复正常、脑组织细胞凋亡数减少（P＜0.01）；TNF-α、IL-6、IL-1β、MDA降低（P＜0.01），SOD升高（P＜0.05、0.01）。通过基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，差异基因富集在受体蛋白酪氨酸激酶结合生物过程及PI3K/Akt信号通路，复方高滋斑片可调控该通路基因的异常表达；Western blotting结果显示，复方高滋斑片可使Bcl-2、PI3K、p-Akt/Akt蛋白水平增加，Bax和Caspase-3蛋白水平减少。结论 复方高滋斑片对脑缺血再灌注损伤具有一定的改善作用，该作用与调节受体蛋白酪氨酸激酶结合生物过程及通过激活PI3K/Akt信号通路减少脑缺血再灌注后的神经元凋亡相关。

Objective To investigate the protective effect of Compound Gaoziban Tablets on cerebral ischemia-reperfusion injury (CIRI) and the underlying mechanisms. Methods Seventy-two male Sprague-Dawley (SD) rats were randomly divided into a sham operation group, a model group, low‑, medium‑, and high‑dose (135, 270, 540 mg/kg) Compound Gaoziban Tablets groups, and Atorvastatin Calcium Tablets group, with 12 rats in each group. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion. After modeling, the survival rate, body weight, and Zea Longa score of rats in each group were analyzed. Hematoxylin-eosin (HE) staining was used to detect morphological changes in brain tissue, and TUNEL staining was performed to analyze apoptosis in brain tissue. Serum levels of inflammatory factors including tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6), and IL‑1β, as well as oxidative stress indicators malondialdehyde (MDA) and superoxide dismutase (SOD), were measured by ELISA. Transcriptome sequencing was used to predict signaling pathways related to the protective effect of Compound Gaoziban Tablets against cerebral ischemia-reperfusion injury, and the expression of genes related to these pathways was detected by RT‑PCR. Western blotting was used to determine the protein expression of phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) pathway‑related proteins and apoptosis‑related proteins including B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), and cysteinyl aspartate‑specific protease‑3 (Caspase‑3) in the ischemic penumbra. Results Compared with the model group, Compound Gaoziban Tablets increased the survival rate and body weight, and decreased the Zea Longa score in rats (P < 0.01). It promoted the recovery of normal brain tissue morphology, and reduced the number of apoptotic brain tissue cells (P < 0.01). The levels of TNF-α, IL-6, IL-1β, and MDA were decreased (P < 0.01), while SOD was increased (P < 0.05, 0.01). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that differentially expressed genes were enriched in receptor protein tyrosine kinase binding biological processes and the PI3K/Akt signaling pathway. Compound Gaoziban Tablets could regulate the abnormal expression of genes in this pathway. Western blotting results showed that Compound Gaoziban Tablets upregulated the protein levels of Bcl-2, PI3K, and p-Akt/Akt, and downregulated the protein levels of Bax and Caspase-3. Conclusion Compound Gaoziban Tablets exert a marked protective effect against cerebral ischemia–reperfusion injury, an effect associated with modulation of receptor protein-tyrosine kinase binding and activation of the PI3K–AKT pathway, thereby reducing post-ischemic neuronal apoptosis.

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“天山英才”医药卫生高层次人才培养计划项目（TSYC202301B152）； 天山创新团队项目（2024D14018）；中央引导地方资金项目（ZYYD2024JD06）