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Mutations in the Na-K-2Cl co-transporter NKCC2 lead to type I Bartter syndrome, a life-threatening kidney disease. We previously showed that export from the ER constitutes the limiting step in NKCC2 maturation and cell surface expression. Yet, the molecular mechanisms involved in this process remain obscure. Here, we report the identification of chaperone stress 70 protein (STCH) and the stress-inducible heat shock protein 70 (Hsp70), as two novel binding partners of the ER-resident form of NKCC2. STCH knock-down increased total NKCC2 expression whereas Hsp70 knock-down or its inhibition by YM-01 had the opposite effect. Accordingly, overexpressing of STCH and Hsp70 exerted opposite actions on total protein abundance of NKCC2 and its folding mutants. Cycloheximide chase assay showed that in cells over-expressing STCH, NKCC2 stability and maturation are heavily impaired. In contrast to STCH, Hsp70 co-expression increased NKCC2 maturation. Interestingly, treatment by protein degradation inhibitors revealed that in addition to the proteasome, the ER associated degradation (ERAD) of NKCC2 mediated by STCH, involves also the ER-to-lysosome-associated degradation pathway. In summary, our data are consistent with STCH and Hsp70 having differential and antagonistic effects with regard to NKCC2 biogenesis. These findings may have an impact on our understanding and potential treatment of diseases related to aberrant NKCC2 trafficking and expression.  相似文献   
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王佳馨  杨关林  彭博 《金属学报》2019,24(2):205-211
目的: 探讨平肝滋阴通瘀方联合苯磺酸氨氯地平治疗高血压的临床疗效。方法: 2017年6月至2018年6月将符合纳入标准的90例患者随机分为治疗组和对照组,每组患者45例,对照组予苯磺酸氨氯地平,治疗组在对照组单纯西药的基础上加用平肝滋阴通瘀方,治疗15 d后观察两组临床治疗效果。结果: 治疗组患者的总有效率、血压下降水平、中医证候和生活质量改善情况均优于对照组(P<0.05)。结论: 平肝滋阴通瘀方联合苯磺酸氨氯地平治疗高血压疗效显著,不良反应发生率低,可进一步临床推广应用。  相似文献   
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叶鹏  谭兴  冷岳奇  王杨凯  王伟忠 《金属学报》2021,26(12):1335-1343
高血压病是一种危害人类健康的严重疾病,尽管高血压的临床治疗已经取得较好疗效,但仍存在不少药物耐受性等不同类型的顽固性高血压,而且高血压的并发症如心力衰竭、脑卒中等发病率仍居高不下,因此,非药物治疗策略的深入研发与应用已成为高血压治疗的一个重要方面。交感神经系统在高血压发生发展中起着关键性作用,目前大多数高血压防治的非药物治疗技术主要通过靶向调节机体交感神经功能来实现,这些技术主要包括深部脑刺激、肾动脉神经射频消融术、中央髂动静脉吻合术、压力反射激活疗法、血管内压力反射放大疗法、颈动脉体切除术等。本综述重点对上述基于交感神经系统的非药物治疗方法的应用现状和相关优缺点进行回顾总结,为高血压的有效治疗提供新思路和多重选择。  相似文献   
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目的 探究尾静脉注射短链酰基辅酶A脱氢酶(SCAD)重组腺病毒能否改善自发性高血压大鼠(SHR)血管重构。方法 实验分为6组:Wistar+NS组、Wistar+GFP组、Wistar+Ad-SCAD组、SHR+NS组、SHR+GFP组和SHR+Ad-SCAD组。腺病毒包装的SCAD和GFP纯化后,以尾静脉方式注射给药8周。采用超声心动图检测大鼠心功能情况;采用无创血压仪检测大鼠的血压变化;主动脉HE染色、天狼星红染色、DHE染色、TUNEL染色、EVG染色,观察血管重构。采用实时荧光定量PCR检测相关基因mRNA表达变化、Western blot检测相关蛋白表达变化,观察游离脂肪酸、一氧化氮(NO)和ATP含量变化。结果 (1)尾静脉注射SCAD重组腺病毒,大鼠主动脉中SCAD蛋白出现过表达,mRNA水平增高,SCAD酶活性增加;(2)在病理状态下,增加主动脉中SCAD表达,可以降低血压,改善心功能,改善血管管腔大小,减少胶原沉积,减少血管活性氧(ROS)的生成和细胞凋亡;(3)在病理状态下,SCAD的表达增加可减少血清和主动脉中游离脂肪酸的含量,增加组织中的ATP水平,激活内皮型一氧化氮合酶(eNOS)磷酸化,增加主动脉NO的生成。结论 自发性高血压大鼠主动脉SCAD的表达增加能逆转高血压血管重构,可能与其减少血清中游离脂肪酸的含量、增加NO水平、减少活性氧生成、消除氧化应激有关。  相似文献   
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A cross-sectional study was conducted to investigate the impact of solid fuel use for heating and cooking on blood pressure (BP) and hypertension, using data from the China Health and Retirement Longitudinal Study (CHARLS). The primary fuels used for indoor heating and cooking were collected by questionnaires, respectively. Hypertension was defined based on self-report of physician's diagnosis, and/or measured BP, and/or anti-hypertensive medication use. Multivariate logistic regression models were constructed to assess the associations. Among 10 450 eligible participants, 68.2% and 57.2% used indoor solid fuel for heating and cooking, respectively. Compared with none/clean fuel users, solid fuel for heating was associated with elevated BP (adjusted β: 2.02, 95% CI: 1.04–3.01 for systolic BP; adjusted β: 1.36, 95% CI: 0.78–1.94 for diastolic BP) and increased risk of hypertension (adjusted odds ratio: 1.15, 95% CI: 1.03–1.29). The impact of indoor solid fuel for heating on BP was more evident in rural and north residents, and hypertensive patients. We did not detect any significant associations between solid fuel use for cooking and BP/hypertension. Indoor solid fuel use is prevalent in China, especially in the rural areas. Its negative impact on BP suggested that modernization of household fuel use may help to reduce the burden of hypertension in China.  相似文献   
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Essential oils (EO) are complex secondary metabolites, which are produced by aromatic plants and identified by their powerful odors. Present studies on EO and their isolated ingredients have drawn the attention of researchers to screen these natural products and evaluate their effect on the cardiovascular system. Some EO, and their active ingredients, have been reported to improve the cardiovascular system significantly by affecting vaso-relaxation, and decreasing the heart rate and exert a hypotension activity. Several mechanisms have been proposed for the role of EO and their main active components in promoting the health of the cardiovascular system. The objective of this review is to highlight the current state of knowledge on the functional role of EO extracted from plants for reducing the risk of cardiovascular diseases and their mechanisms of action. Research on EO has the potential to identify new bioactive compounds and formulate new functional products for the treatment of cardiovascular diseases such as arterial hypertension, angina pectoris, heart failure, and myocardial infarction.  相似文献   
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