Qingda Granules alleviate brain damage in spontaneously hypertensive rats by modulating the miR-124/STAT3 signaling axis.

Q3 Medicine

南方医科大学学报杂志 Pub Date : 2025-01-20 DOI:10.12122/j.issn.1673-4254.2025.01.03

Qiaoyan Cai, Yaoyao Xu, Yuxing Lin, Haowei Lin, Junpeng Zheng, Weixiang Zhang, Chunyu Zhao, Yupeng Lin, Ling Zhang

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引用次数: 0

Abstract

Objectives: To explore the mechanism of Qingda Granules (QDG) for alleviating brain damage in spontaneously hypertensive rats (SHRs).

Methods: Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks. The control rats, along with 6 age-matched WKY rats, were treated with saline only. Blood pressure changes of the rats were monitored, and pathologies and neuronal apoptosis in the cerebral cortex were examined with HE staining and TUNEL staining. Cerebral cortical expressions of miR-124 and STAT3 mRNA were detected using RT-qPCR, and the protein expressions of NeuN, STAT3, Bcl-2, Bax, and cleaved caspase-3 were detected with immunohistochemistry and Western blotting. In a HT22 cell model of oxygen and glucose deprivation/reoxygenation (OGD/R), the effects of QDG on cell viability and apoptosis, expressions of miR-124 and STAT3 mRNA, and protein expressions of STAT3, Bcl-2, Bax, and cleaved caspase-3 were evaluated using CCK8 assay, Hoechst 33342 staining, RT-qPCR, and Western blotting.

Results: Compared with WKY rats, SHRs had significantly elevated systolic blood pressure, diastolic blood pressure and mean arterial pressure with significantly increased neuronal apoptosis in the cerebral cortex, reduced expressions of NeuN, miR-124 and Bcl-2, and enhanced expressions of STAT3, Bax and cleaved caspase-3 (P<0.05). All these changes in the SHRs were significantly ameliorated by treatment with QDG (P<0.05). In the HT22 cell model, QDG treatment obviously reduced OGD/R-induced cell apoptosis, increased the expressions of miR-124 and Bcl-2, and suppressed the elevation of protein expressions of STAT3, Bax and cleaved caspase-3.

Conclusions: QDG inhibits cerebral cortical neuronal apoptosis and thereby attenuates brain damage in SHR rats by modulating the miR-124/STAT3 signaling axis.

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清大颗粒通过调节miR-124/STAT3信号轴减轻自发性高血压大鼠脑损伤。

目的：探讨清大颗粒减轻自发性高血压大鼠脑损伤的作用机制。方法：将12只5周龄的SHR随机分为SHR对照组和SHR+QDG组，QDG以每天0.9 g/kg的剂量灌胃，连续12周。对照大鼠和6只年龄相匹配的WKY大鼠只接受生理盐水治疗。采用HE染色、TUNEL染色观察大鼠血压变化，观察大鼠大脑皮层病理变化及神经元凋亡情况。RT-qPCR检测小鼠大脑皮层miR-124和STAT3 mRNA的表达，免疫组织化学和Western blotting检测NeuN、STAT3、Bcl-2、Bax和cleaved caspase-3蛋白的表达。在氧和葡萄糖剥夺/再氧化（OGD/R） HT22细胞模型中，采用CCK8法、Hoechst 33342染色、RT-qPCR和Western blotting检测QDG对细胞活力和凋亡、miR-124和STAT3 mRNA表达以及STAT3、Bcl-2、Bax和cleaved caspase-3蛋白表达的影响。结果：与WKY大鼠相比，SHR大鼠收缩压、舒张压和平均动脉压明显升高，大脑皮层神经元凋亡明显增加，NeuN、miR-124、Bcl-2表达降低，STAT3、Bax、cleaved - caspase-3表达增强（ppp）。结论：QDG通过调节miR-124/STAT3信号轴抑制SHR大鼠大脑皮层神经元凋亡，从而减轻脑损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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