PDF(Pubmed)
Abstract：
BACKGROUND: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs).
METHODS: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury.
RESULTS: Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury.
CONCLUSIONS: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.
METHODS: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury.
RESULTS: Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury.
CONCLUSIONS: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.
摘要：
背景：在本次调查中，我们探讨了药物胆碱能刺激对自发性高血压大鼠急性心肌梗死（AMI）后心功能和肾脏炎症的影响。
方法：成年男性SHR被随机分为三个实验组：假手术；AMIVeh（梗塞，用媒介物治疗)；和AMI+PY(梗塞，用胆碱酯酶抑制剂治疗，溴化吡啶斯的明（PY）-40mg/kg，每天一次，连续七天)。在手术后7或30天对大鼠实施安乐死。在安乐死前一天评估临床参数。安乐死之后,收集血样,收集肾组织,进行组织学和基因表达分析,以评估炎症和损伤.
结果：手术后七天，AMI+PY组表现出左心室舒张功能和自主神经调节的改善，与AMI+Veh组相比，肾巨噬细胞浸润减少。此外，促炎基因表达显著下调,抗炎基因表达上调.术后30天分析显示，PY治疗对肾脏基因表达有持续的积极作用，与生物标志物的减少相关，指示亚临床肾损伤。
结论：PY短期胆碱能刺激通过减轻AMI后的炎症反应提供心脏和肾脏保护。
方法：成年男性SHR被随机分为三个实验组：假手术；AMIVeh（梗塞，用媒介物治疗)；和AMI+PY(梗塞，用胆碱酯酶抑制剂治疗，溴化吡啶斯的明（PY）-40mg/kg，每天一次，连续七天)。在手术后7或30天对大鼠实施安乐死。在安乐死前一天评估临床参数。安乐死之后,收集血样,收集肾组织,进行组织学和基因表达分析,以评估炎症和损伤.
结果：手术后七天，AMI+PY组表现出左心室舒张功能和自主神经调节的改善，与AMI+Veh组相比，肾巨噬细胞浸润减少。此外，促炎基因表达显著下调,抗炎基因表达上调.术后30天分析显示，PY治疗对肾脏基因表达有持续的积极作用，与生物标志物的减少相关，指示亚临床肾损伤。
结论：PY短期胆碱能刺激通过减轻AMI后的炎症反应提供心脏和肾脏保护。
