气压反射传入功能是莱普汀介导的血压降低和莱普汀抵抗性高血压见解的一部分

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-02-29 DOI:10.1016/j.npep.2024.102418
Shi-gang Ren , Dong-mei Li , Hua Liu
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引用次数: 0

摘要

本研究旨在验证瘦素对血压(BP)调节的影响,以及瘦素通过气压反射传入和调节失调对代谢性/神经源性高血压的抵抗。在对成年雌性大鼠的NG神经元进行微量瘦素注射的同时测量动脉血压/心率(HR),并通过全细胞贴片获取NG神经元的膜去极化/内向电流。用 PE/SNP 测试了对照组和高果糖饮食诱发的高血压(HTN-HFD)大鼠的气压反射敏感性(BRS),用固定染色和 qRT-PCR 检测了 Leptin/受体在 NG/孤束核(NTS)中的分布/表达,用 ELISA 测定了血清中 Leptin/NE 的浓度。结果表明,Leptin NG 显微注射可显著/剂量依赖性地降低血压,这可能是通过直接兴奋雌性特异性的 Ah 型神经元亚群而实现的,这些神经元亚群显示出强大的膜去极化/内向电流。在 NG 中检测到的 OB-Ra/OB-Rb 的性别特异性分布/表达具有雌激素依赖性,类似的观察结果在 NTS 中也得到了证实。正如预期的那样,在 PE/SNP 的作用下,雄性和雌性大鼠的 BRS 都会急剧下降,只有雌性大鼠在特定浓度的 PE 作用下除外。此外,HFD-HTN 模型大鼠血清中的瘦素浓度升高,雌性更为明显。在高血压条件下,NG/NTS中OB-R的平均荧光密度和OB-Ra/OB-Rb的mRNA表达均显著下调。这些结果表明,瘦素通过气压反射传入激活在副交感神经驱动中起主导作用,从而在系统上缓冲瘦素介导的交感神经激活,瘦素抵抗是通过气压反射传入失调导致代谢性/神经源性高血压的一种不可忽视的机制。
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Baroreflex afferent function is a part of insights of Leptin-mediated blood pressure reduction and Leptin-resistance hypertension

The aim of this study is to verify the impact of Leptin in blood pressure (BP) regulation and Leptin-resistance in metabolic/neurogenic hypertension through baroreflex afferents and dysregulation. Artery BP/heart rate (HR) were measured while nodose (NG) microinjection of Leptin, membrane depolarization/inward current were obtained by whole-cell patch from NG neurons isolated from adult female rats. Baroreflex sensitivity (BRS) tested with PE/SNP, distribution/expression of Leptin/receptors in the NG/nucleus tractus solitary (NTS) examined using immumostaining and qRT-PCR, and serum concentrations of Leptin/NE measured by ELISA were observed in control and high fructose-drinking induced hypertension (HTN-HFD) rats. The results showed that BP was significantly/dose-dependently reduced by Leptin NG microinjection likely through direct excitation of female-specific subpopulation of Ah-type neurons showing a potent membrane depolarization/inward currents. Sex-specific distribution/expression of OB-Ra/OB-Rb in the NG were detected with estrogen-dependent manner, similar observations were also confirmed in the NTS. As expected, BRS was dramatically decreased in the presence of PE/SNP in both male and female rats except for the female with PE at given concentrations. Additionally, serum concentration of Leptin was elevated in HFD-HTN model rats of either sex with more obvious in females. Under hypertensive condition, the mean fluorescent density of OB-R and mRNA expression for OB-Ra/OB-Rb in the NG/NTS were significantly down-regulated. These results have demonstrated that Leptin play a role in dominant parasympathetic drive via baroreflex afferent activation to buffer Leptin-mediated sympathetic activation systemically and Leptin-resistance is an innegligible mechanism for metabolic/neurogenic hypertension through baroreflex afferent dysregulation.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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