慢性心力衰竭患者的骨量丢失与交感神经激活有关。
Bone mass loss in chronic heart failure is associated with sympathetic nerve activation.
机构信息
Department of Orthopedics, Peking University Third Hospital, Beijing, China.
Department of Orthopedics, Peking University Third Hospital, Beijing, China; Beijing Key Laboratory of Spinal Diseases, Beijing, China.
出版信息
Bone. 2023 Jan;166:116596. doi: 10.1016/j.bone.2022.116596. Epub 2022 Oct 25.
PURPOSE
Chronic heart failure causes osteoporosis, but the mechanism remains unclear. The sympathetic nerve plays an important role in both bone metabolism and cardiovascular function.
METHODS
Thirty-six adult male SD rats were randomly divided into the following four groups: sham surgery (Sham) group, guanethidine (GD) group, abdominal transverse aorta coarctation-induced heart failure + normal saline (TAC) group, and TAC + guanethidine (TAC + GD) group. Normal saline (0.9 % NaCl) or guanethidine (40 mg/kg/ml) was intraperitoneally injected daily for 5 weeks. Then, DXA, micro-CT, ELISA and RT-PCR analyses were performed 12 weeks after treatment.
RESULTS
The bone loss in rats subjected to TAC-induced chronic heart failure and chemical sympathectomy with guanethidine was increased. Serum norepinephrine levels were increased in rats with TAC-induced heart failure but were decreased in TAC-induced heart failure rats treated with guanethidine. The expression of α2A adrenergic receptor, α2C adrenergic receptor, osteoprotegerin (OPG), and osteocalcin in the tibia decreased in the TAC-induced heart failure group, and the expression of β1 adrenergic receptor, β2 adrenergic receptor, receptor activator of nuclear factor-κ B ligand (RANKL), and RANKL/OPG in the tibia increased in the heart failure group. In addition, these changes in gene expression levels were rescued by chemical sympathectomy with guanethidine.
CONCLUSIONS
TAC-induced chronic heart failure is associated with bone mass loss, and the sympathetic nerve plays a significant role in heart failure-related bone mass loss.
MINI ABSTRACT
The present study supports the hypothesis that heart failure is related to bone loss, and the excessive activation of sympathetic nerves participates in this pathophysiological process. The present study suggests a potential pathological mechanism of osteoporosis associated with heart failure and new perspectives for developing strategies for heart failure-related bone loss.
目的
慢性心力衰竭可导致骨质疏松症，但发病机制尚不清楚。交感神经在骨骼代谢和心血管功能中均发挥着重要作用。
方法
36 只成年雄性 SD 大鼠随机分为以下四组：假手术（Sham）组、胍乙啶（GD）组、腹主动脉缩窄致心力衰竭+生理盐水（TAC）组、TAC+胍乙啶（TAC+GD）组。每天分别经腹腔注射生理盐水（0.9%NaCl）或胍乙啶（40mg/kg/ml），连续 5 周。治疗 12 周后进行 DXA、micro-CT、ELISA 和 RT-PCR 分析。
结果
TAC 诱导的慢性心力衰竭大鼠和化学性交感神经切除术（胍乙啶）后骨丢失增加。TAC 诱导心力衰竭大鼠的血清去甲肾上腺素水平升高，但用胍乙啶治疗的 TAC 诱导心力衰竭大鼠的血清去甲肾上腺素水平降低。TAC 诱导心力衰竭大鼠的胫骨中α2A 肾上腺素能受体、α2C 肾上腺素能受体、骨保护素（OPG）和骨钙素表达降低，β1 肾上腺素能受体、β2 肾上腺素能受体、核因子-κB 配体（RANKL）和 RANKL/OPG 表达增加。此外，胍乙啶的化学性交感神经切除术可挽救这些基因表达水平的变化。
结论
TAC 诱导的慢性心力衰竭与骨量减少有关，交感神经在心力衰竭相关的骨量减少中起重要作用。
摘要
本研究支持心力衰竭与骨丢失相关的假说，并且交感神经的过度激活参与了这一病理生理过程。本研究为心力衰竭相关骨质疏松症的潜在病理机制提供了新的见解，并为开发心力衰竭相关骨丢失的策略提供了新的视角。
Zotero 插件