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Effect of the traditional Chinese medicine Pinggan-Qianyang decoction on SIRT1–PTEN signaling in vascular aging in spontaneously hypertensive rats
Hypertension Research ( IF 4.3 ) Pub Date : 2021-06-29 , DOI: 10.1038/s41440-021-00682-6
Zhang Cui 1, 2 , Yao Jiamei 1, 2 , Yang Yushu 1, 2 , Fang Xia 1, 2 , Yang Haiyan 1, 2 , Dan Zhang 1, 2 , Chen Qiong 1, 2 , Zhong Guangwei 1, 2
Affiliation  

Age-related functional decline is a physiological phenomenon that occurs in all organ systems. However, the acceleration and early occurrence of this process are observed in cardiovascular pathologies, including hypertension. This study aimed to investigate SIRT1–PTEN signaling in aortic tissue from spontaneously hypertensive rats (SHRs) and changes in SIRT1 and PTEN expression following treatment with Pinggan-Qianyang decoction (PGQYD) and explore the mechanism involved in the treatment of hypertensive vascular aging with traditional Chinese medicine. In this study, we used two rat models: spontaneously hypertensive rats (SHRs) at 14 and 64 weeks of age and WKY rats at 64 weeks of age. The degree of irritability and rotation tolerance time were evaluated to determine the effects of PGQYD on animal behavior. The morphology of the thoracic aorta was examined by hematoxylin-eosin (HE) and Masson staining and electron microscopy. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and superoxide dismutase (SOD) and anti-superoxide anion content were detected. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to observe the thoracic aorta during vascular aging. RT-qPCR, immunofluorescence, and Western blot analysis were performed to detect changes in the mRNA and protein expression of p53, p21, SIRT1, and PTEN in rat aortic tissues. Behavioral tests and histological and morphological analyses showed the remarkable amelioration of vascular aging after PGQYD treatment compared with that in the older SHRs. Moreover, PGQYD significantly decreased vascular aging in SHRs, as indicated by reduced SA-β-Gal staining, NADPH oxidase activity, and p53 and p21 expression, and increased anti-superoxide anion and SOD content. Furthermore, PGQYD increased SIRT1 and PTEN expression, but the downregulated expression of SIRT1 induced by a SIRT1 inhibitor abolished the PGQYD-induced antiaging effects on gene expression and antioxidant activity and enhanced PTEN expression. PGQYD could ameliorate vascular aging effects in SHRs, which may have been mediated via the regulation of SIRT1–PTEN signaling in aortic tissue.



中文翻译:

中药平肝千阳汤对自发性高血压大鼠血管衰老中SIRT1-PTEN信号通路的影响

与年龄相关的功能衰退是一种生理现象,发生在所有器官系统中。然而,在包括高血压在内的心血管疾病中观察到这一过程的加速和早期发生。本研究旨在探讨自发性高血压大鼠(SHRs)主动脉组织中SIRT1-PTEN信号通路及平肝潜阳汤(PGQYD)治疗后SIRT1和PTEN表达的变化,探讨中药治疗高血压血管衰老的机制。中药。在这项研究中,我们使用了两种大鼠模型:14 和 64 周龄的自发性高血压大鼠 (SHR) 和 64 周龄的 WKY 大鼠。评估烦躁程度和旋转耐受时间以确定 PGQYD 对动物行为的影响。通过苏木精-伊红(HE)和Masson染色和电子显微镜检查胸主动脉的形态。检测烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活性和超氧化物歧化酶(SOD)和抗超氧阴离子含量。衰老相关β-半乳糖苷酶(SA-β-Gal)染色用于观察血管老化过程中的胸主动脉。进行 RT-qPCR、免疫荧光和蛋白质印迹分析以检测大鼠主动脉组织中 p53、p21、SIRT1 和 PTEN 的 mRNA 和蛋白质表达的变化。行为测试和组织学和形态学分析显示,与老年 SHR 相比,PGQYD 治疗后血管老化显着改善。此外,PGQYD 显着降低 SHR 中的血管老化,如 SA-β-Gal 染色减少所示,NADPH氧化酶活性,p53和p21表达,抗超氧阴离子和SOD含量增加。此外,PGQYD 增加了 SIRT1 和 PTEN 的表达,但由 SIRT1 抑制剂诱导的 SIRT1 的表达下调消除了 PGQYD 诱导的对基因表达和抗氧化活性的抗衰老作用,并增强了 PTEN 的表达。PGQYD 可以改善 SHR 中的血管老化效应,这可能是通过调节主动脉组织中的 SIRT1-PTEN 信号传导来介导的。

更新日期:2021-06-29
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