三七花总皂苷通过抑制补体 3 激活肾素-血管紧张素-醛固酮系统对代谢性高血压大鼠的有益作用。
Beneficial effects of Panax notoginseng (Burkill) F. H. Chen flower saponins in rats with metabolic hypertension by inhibiting the activation of the renin-angiotensin-aldosterone system through complement 3.
机构信息
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.
出版信息
BMC Complement Med Ther. 2023 Jan 18;23(1):13. doi: 10.1186/s12906-022-03828-2.
BACKGROUND
Metabolic hypertension (MH) has become the most common type of hypertension in recent years due to unhealthy eating habits and lifestyles of people, such as over-eating alcohol, high fat, and sugar diets (ACHFSDs). Therefore, effective means to combat MH are needed. Previous studies have shown that Panax notoginseng (Burkill) F. H. Chen flower saponins (PNFS) can lower blood pressure in spontaneously hypertensive rats (SHR). However, whether it acts on MH and its mechanism of action remain unclear. METHODS: The pharmacodynamic effects of PNFS were evaluated in rats with ACHFSDs-induced MH. The blood pressure, blood biochemical, grip strength, face temperature, vertigo time, and liver index were estimated. The histological changes in the liver and aorta were observed using hematoxylin and eosin staining. The levels of ET-1, TXB, NO, PGI, Renin, ACE, Ang II, and ALD in plasma were detected using ELISA. The levels of C3, KLF5, LXRα, and Renin in kidney tissues were measured using qRT-PCR.The expression levels of C3, KLF5, LXRα, and Renin in kidney tissues were examined using Western blotting.
RESULTS
In the present study, PNFS was found to reduce blood pressure, face temperature, and vertigo time, increase grip strength and improve dyslipidemia in rats with MH. In addition, PNFS decreased the plasma levels of ET-1 and TXB, elevated the levels of NO and PGI, and improved pathological aortic injury. Meanwhile, PNFS decreased the plasma levels of Renin, ACE, Ang II, and ALD. QRT-PCR and Western bolt showed that PNFS downregulated C3, KLF5, LXRα, and Renin protein and mRNA expression in the kidneys of rats with MH.
CONCLUSION
The finding of the present study suggested that PNFS could downregulate C3 and KLF-5 expression in rats with MH, thereby inhibiting the overactivation of the renin-angiotensin-aldosterone system, while improving vascular endothelial function and ultimately reducing blood pressure in rats with MH.
背景
由于人们不健康的饮食习惯和生活方式，如过度饮酒、高脂肪和高糖饮食（ACHFSDs），代谢性高血压（MH）已成为近年来最常见的高血压类型。因此，需要有效的手段来对抗 MH。先前的研究表明，三七花总皂苷（PNFS）可以降低自发性高血压大鼠（SHR）的血压。然而，它是否作用于 MH 及其作用机制尚不清楚。
方法
在 ACHFSDs 诱导的 MH 大鼠中评价 PNFS 的药效学作用。评估血压、血液生化指标、握力、面部温度、眩晕时间和肝指数。使用苏木精和伊红染色观察肝和主动脉的组织学变化。使用 ELISA 检测血浆中 ET-1、TXB、NO、PGI、肾素、ACE、Ang II 和 ALD 的水平。使用 qRT-PCR 测量肾组织中 C3、KLF5、LXRα 和肾素的水平。使用 Western blot 检测肾组织中 C3、KLF5、LXRα 和肾素的表达水平。
结果
本研究发现，PNFS 可降低 MH 大鼠的血压、面部温度和眩晕时间，增加握力，改善血脂异常。此外，PNFS 降低了血浆中 ET-1 和 TXB 的水平，升高了 NO 和 PGI 的水平，并改善了主动脉的病理损伤。同时，PNFS 降低了血浆中 Renin、ACE、Ang II 和 ALD 的水平。qRT-PCR 和 Western blot 显示，PNFS 下调了 MH 大鼠肾脏中 C3、KLF5、LXRα 和 Renin 蛋白和 mRNA 的表达。
结论
本研究结果表明，PNFS 可下调 MH 大鼠的 C3 和 KLF-5 表达，从而抑制肾素-血管紧张素-醛固酮系统的过度激活，同时改善血管内皮功能，最终降低 MH 大鼠的血压。
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