| 王阅军,赵明明,张昱.加味黄芪赤风汤调节慢性肾小球肾炎系膜细胞凋亡作用机制的网络药理学及实验研究[J].浙江中医药大学学报,2022,46(11):1199-1210. |
| 加味黄芪赤风汤调节慢性肾小球肾炎系膜细胞凋亡作用机制的网络药理学及实验研究 |
| Network Pharmacology and Experimental Study of Modified Huangqi Chifeng Decoction on the Apoptotic Mechanism of Mesangial Cell in Glomerulonephritis |
| DOI：10.16466/j.issn1005-5509.2022.11.004 |
| 中文关键词: 网络药理学 加味黄芪赤风汤 慢性肾小球肾炎 细胞凋亡 系膜细胞 药物靶点 活性成分 实验验证 |
| 英文关键词: network pharmacology modified Huangqi Chifeng decoction chronic glomerulonephritis cell apoptosis mesangial cells drug targets active components experimental verification |
| 基金项目:国家自然科学基金面上项目(81873300) |
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| 中文摘要: |
| [目的] 结合网络药理学及实验验证，探索加味黄芪赤风汤对慢性肾小球肾炎的潜在作用机制。[方法] 通过多个药物靶点数据库，构建加味黄芪赤风汤作用于慢性肾小球肾炎的“药物-成分-靶点”网络，并对作用靶点进行富集分析，并进一步进行实验验证。[结果] 加味黄芪赤风汤治疗慢性肾小球肾炎的“药物-成分-靶点”网络共包含184个疾病靶点基因，富集分析结果提示其作用靶点主要集中在细胞凋亡相关通路。系膜细胞经脂多糖诱导增殖后，使用加味黄芪赤风汤含药血清进行干预，透射电镜观察显示，在中药各剂量组系膜细胞中，均可观察到细胞器减少、聚集及染色质固缩等凋亡相关的超微结构变化。流式细胞仪检测发现中药干预组的系膜细胞凋亡率高于其他组，并呈现剂量依赖性。而免疫印迹实验结果也显示，中药干预组中抗凋亡蛋白B细胞淋巴瘤-2(B-cell lymphoma-2，Bcl-2)的表达量显著减少(P＜0.01)，而促凋亡的Bcl-2相关X(Bcl-2 associated X，Bax)蛋白和半胱氨酸蛋白酶-3的表达量显著升高(P＜0.01)。[结论] 加味黄芪赤风汤可通过调节细胞凋亡，控制系膜细胞的炎性增殖，从而缓解慢性肾小球肾炎的发生和发展。 |
| 英文摘要: |
| [Objective] To explore the mechanism of treating chronic glomerulonephritis with modified Huangqi Chifeng decoction through network pharmacology and experimental validation. [Methods] The“drug-component-target” network of modified Huangqi Chifeng decoction on chronic glomerulonephritis was constructed through multiple drug-target databases， and the enrichment analysis and further experimental verification of the targets were carried out. [Results] The“drug-component-target” network of modified Huangqi Chifeng decoction for chronic glomerulonephritis contained 184 disease target genes， and the results of enrichment analysis suggested that its targets were mainly in apoptosis-related pathways. The results of transmission electron microscopy showed that apoptosis-related ultrastructural changes， such as organelle reduction， organelle aggregation and chromatin shrinkage in mesangial cells could be observed in all dose groups of modified Huangqi Chifeng decoction. Flow cytometry revealed that the apoptosis rate of mesangial cells was higher in modified Huangqi Chifeng decoction intervention group than in the other groups and showed a dose-dependent pattern. Western blot results also showed that the expression of anti-apoptotic B-cell lymphoma-2(Bcl-2) protein was significantly reduced(P＜0.01)， while the expression of pro-apoptotic Bcl-2 associated X(Bax) protein and cysteinyl aspartate specific proteinase-3(caspase-3) protein were significantly increased in modified Huangqi Chifeng decoction group(P＜0.01). [Conclusion] The target and mechanism of modified Huangqi Chifeng decoction in treating chronic glomerulonephritis may be related to its regulation of apoptosis. |
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