Long Linzi, Zhang Xiuli, Wen Ying, Li Jiapeng, Wei Lihui, Cheng Ying, Liu Huixin, Chu Jianfeng, Fang Yi, Xie Qiurong, Shen Aling, Peng Jun
Academy of Integrative Medicine, Fuzhou, China.
Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fuzhou, China.
Front Pharmacol. 2022 Feb 10;12:770863. doi: 10.3389/fphar.2021.770863. eCollection 2021.
Qingda granules (QDG) exhibit antihypertension and multiple-target-organ protection. However, the therapeutic potential of QDG on hypertensive renal injury remains unknown. Therefore, the main objective of the current study is to explore the effects and underlying mechanisms of QDG treatment on renal injury in angiotensin (Ang) II-infused mice. Mice were infused with Ang II (500 ng/kg/min) or saline for 4 weeks with subcutaneously implanted osmotic pumps. After infusion, mice in the Ang II + QDG group were intragastrically administrated with QDG daily (1.145 g/kg/day), whereas the control group and Ang II group were intragastrically administrated with the same amount of double-distilled water. Blood pressure of the mice monitored using the CODA™ noninvasive blood pressure system revealed that QDG treatment significantly attenuated elevated blood pressure. Moreover, hematoxylin-eosin staining indicated that QDG treatment ameliorated Ang II-induced renal morphological changes, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilatation. RNA-sequencing (RNA-seq) identified 662 differentially expressed transcripts (DETs) in renal tissues of Ang II-infused mice, which were reversed after QDG treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis based on DETs in both comparisons of Ang II vs. Control and Ang II + QDG vs. Ang II identified multiple enriched pathways, including apoptosis and p53 pathways. Consistently, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and Annexin V staining revealed that QDG treatment significantly attenuated Ang II-induced cell apoptosis in renal tissues and cultured renal tubular epithelial cell lines (NRK-52E). Furthermore, western blot analysis indicated that Ang II infusion significantly upregulated the protein expression of p53, BCL2-associated X (BAX), cle-caspase-9, and cle-caspase-3, while downregulating the protein expression of BCL-2 in renal tissues, which were attenuated after QDG treatment. Collectively, QDG treatment significantly attenuated hypertensive renal injury, partially by attenuating renal apoptosis and suppressing p53 pathways, which might be the underlying mechanisms.
清大颗粒（QDG）具有降压和多靶点器官保护作用。然而，QDG对高血压肾损伤的治疗潜力尚不清楚。因此，本研究的主要目的是探讨QDG治疗对血管紧张素（Ang）II灌注小鼠肾损伤的影响及其潜在机制。将小鼠通过皮下植入渗透泵以500 ng/kg/min的剂量灌注Ang II或生理盐水4周。灌注后，Ang II + QDG组小鼠每天灌胃给予QDG（1.145 g/kg/天），而对照组和Ang II组小鼠灌胃给予等量的双蒸水。使用CODA™无创血压系统监测小鼠血压，结果显示QDG治疗显著降低了升高的血压。此外，苏木精-伊红染色表明QDG治疗改善了Ang II诱导的肾脏形态学变化，包括肾小球硬化和萎缩、上皮细胞萎缩以及肾小管扩张。RNA测序（RNA-seq）鉴定出Ang II灌注小鼠肾组织中有662个差异表达转录本（DETs），QDG治疗后这些差异表达转录本发生了逆转。基于Ang II与对照组以及Ang II + QDG与Ang II这两个比较中的DETs进行的京都基因与基因组百科全书（KEGG）分析确定了多个富集途径，包括凋亡和p53途径。一致地，末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记（TUNEL）染色和膜联蛋白V染色显示，QDG治疗显著减轻了Ang II诱导的肾组织和培养的肾小管上皮细胞系（NRK-52E）中的细胞凋亡。此外，蛋白质印迹分析表明，Ang II灌注显著上调了肾组织中p53、BCL2相关X蛋白（BAX）、裂解的半胱天冬酶-9和裂解的半胱天冬酶-3的蛋白表达，同时下调了BCL-2的蛋白表达，而QDG治疗后这些变化得到了缓解。总体而言，QDG治疗显著减轻了高血压肾损伤，部分原因是减轻了肾细胞凋亡并抑制了p53途径，这可能是其潜在机制。
Front Pharmacol. 2022-2-10
Front Pharmacol. 2021-7-29
J Ethnopharmacol. 2020-8-10
Front Pharmacol. 2025-5-30
Front Pharmacol. 2021-7-29
Mol Med Rep. 2021-4
Clin Sci (Lond). 2021-1-29
Hypertension. 2020-7
J Ethnopharmacol. 2020-8-10
Zotero 插件
