The HCN channel family comprises of four members (HCN1-4) expressed in the heart and nervous system. The current produced by HCN channels is known as I-h (or I-f or I-q). I-h has also been designated as pacemaker current because it plays a key role in controlling rhythmic activity of cardiac pacemaker cells and spontaneously firing neurons [1]. The diversity of functions that HCN channels perform is partly attributable to differences in their subcellular localization [2]. HCN channels are highly regulated proteins, which respond to different cellular stimuli, they open at hyperpolarizingpotential, carrymixed Na/K current, and are regulated by cyclic nucleotides [3]. These channels play important roles in modulating cellular excitability, rhythmic activity, dendritic integration, and synaptic transmission. HCN channel functions range from setting resting potential, synaptic normalization, gain control, after-hyperpolarization, setting responses in dendrites, mediating cannabinoid role in neuronal plasticity, to the gating of plasticity [4]. These functions have been implicated in a wide range of diseases, including major depressive disorder, neuropathic pain, and multiple subtypes of epilepsy [4,5. Among the four known isoforms, HCN1 is the most expressed in the neocortex and hippocampus. Some studies suggest that coordinated changes in protein expression and surface expression of HCN1 serve as the key regulatory mechanisms controlling the function of the endogenous HCN1 protein in cortical neurons [6]. HCN1 might be involved in reduced vagal modulation and possibly in increased cardiac mortality in schizophrenia patients [7]. HCN2 ion channel activity plays a crucial role in the progress of peripheral neuropathic pain (PNP). Some studies suggest that HCN2 contributes to the development of neuropathic pain by inducing spinal LTP via activation of NMDA receptor-mediated CaMKII signaling, decreased HCN2 channel expression attenuates neuropathic pain by inhibiting pro-inflammatory reactions and NF-kappa B activation[8,9] Like all other HCNs, hHCN3 was inhibited rapidly and reversibly by extracellular cesium and slowly and irreversibly by extracellular applied ZD7288. The human channel was not modulated by intracellular cAMP, a hallmark of the other known HCN channels so the missing response to cAMP distinguishes human HCN3 from both the well cAMP responding HCN subtypes 2 and 4 and the weak responding subtype 1[10]. Upregulation of HCN3 channels in IGL neurons is essential for intrinsic excitability and rhythmic burst firing, and PIP2 serves as a powerful modulator of I-h-dependent properties via an effect on HCN3 channel gating[11]. HCN4 is expressed in brain regions relevant to mood and anxiety disorders including specific thalamic nuclei, the basolateral amygdala, and the midbrain dopamine system[12].

感受风邪是引发鼻鼽、咳嗽、哮病、喘证、肺胀等肺系疾病的重要诱因和首发病因,国医大师晁恩祥从风论治肺系疾病,提出了"风咳"、"风哮"等理论,杨道文教授师法于晁老,在临床上治疗肺系疾病重视"风邪"为患的作用,重视祛除风邪,应用"风药"治疗过敏性鼻炎、哮喘、慢阻肺等肺系疾病有着丰富的经验,本文总结杨道文教授应用"风药"治疗肺系疾病的相关理论和用药经验.

杨道文教授结合小儿生理特点及小儿CARAS的临床特征,认为主要病机是风邪致病、正气亏虚和气机失调,其中强调风邪致病需注意外风与内风并重,正气亏虚主要表现在脾肺两脏.从治风、补虚、调气三方面组方化裁论治.治风时以辛散治外风,以镇敛治内风;补虚时注重肺脾两脏,且补脾之中兼顾运脾;调气时强调肺胃同降,以降为主,降中寓宣.附典型案例1则,以资验证.

咽喉反流性疾病(LPRD)是临床常见疾病,以咽喉异物感、慢性咳嗽、声音嘶哑等为典型症状.杨道文教授从事肺系疾病治疗20余年,对于此疾病治疗有独到见解,认为气的升降运动是生命的根本,LPRD病位在肝肺胃,气机失调、升降无序是其主要病机、并提出肝—肺—胃一体观,以调畅气机,升降相因法治疗此疾病.杨教授对于LPRD的病因病机认识及采取的治疗方法,体现在临床典型医案也,反映杨道文教授治疗咽喉反流性疾病的学术思想.

拔罐法是临床上常用的中医外治方法,背俞穴是脏腑气血流注于背部的穴位总称.背俞穴拔罐可调节对应脏腑功能,治疗相关疾病[1,2].随着人们饮食结构及生活习惯的变化,痛风逐渐成为影响人类健康的第四大代谢性疾病,而拔罐法因为其安全有效、操作简便等优势,越来越多被应用于痛风的治疗中.背俞穴拔罐治疗痛风虽已有较充实的理论基础,临床研究及案例报道却较少[3].笔者跟从导师杨道文教授治疗相关病患20余例,颇有疗效.本文从痛风的病因病机认识、背俞穴拔罐治疗痛风的理论基础及临床应用方面进行阐述,以期为临床治疗痛风开拓思路.

p38促分裂原活化的蛋白激酶(MAPK)信号通路是人体内最关键的细胞内信号通路之一,参与许多呼吸系统疾病的发生、发展.一方面,p38 MAPK信号通路可与糖皮质激素受体(GR)相互调节介导炎症相关反应;另一方面,p38 MAPK信号通路可影响GR对糖皮质激素的敏感性.与p38 MAPK信号通路相关的上下游因子及基因位点在哮喘、慢性阻塞性肺疾病、急性肺损伤、鼻窦炎-鼻息肉等常见呼吸系统疾病中不断被发现.因此,深入研究p38 MAPK信号通路对GR的调控机制,对未来研究新药、提高相关疾病临床疗效均具有重要意义.

肌肉疼痛作为非呼吸系统表现在新型冠状病毒肺炎(COVID-19)临床症状中占比较高,病理机制上可由疾病本身及药物不良反应等导致,临床发现中药在改善此类症状方面独具优势.COVID-19患者肌肉疼痛的病因与湿毒相关,病机为湿毒侵袭、气机痹阻,治疗以祛湿化浊、调畅气机为则,审证求因.通过对病因病机、中医治疗、现代医学肌肉疼痛相关研究的阐述,以期能为COVID-19的中医辨治提供诊疗思路.

目的:探讨平风降气汤对慢性阻塞性肺疾病(COPD)稳定期患者的疗效及对机体氧化应激水平的影响.方法:选取COPD稳定期患者76例,随机分为治疗组和对照组,每组38例.对照组予布地奈德福莫特罗粉吸入剂吸入,治疗组在对照组的基础上加用平风降气汤,观察两组治疗前后肺功能、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)的变化,评价疗效.结果:两组治疗后,咳嗽、咳痰、喘息积分均较治疗前显著降低(P＜0.05,P＜0.01),治疗组咳痰积分显著低于对照组(P＜0.01);肺功能均较治疗前有升高趋势,治疗组肺功能FEV1显著高于对照组(P＜0.05);两组SOD水平显著升高(P＜o.05),治疗组GSH-PX水平显著高于对照组(P＜0.05).结论:平风降气汤可提升COPD稳定期肺功能,改善氧化应激损伤.

目的:观察益气疏风降胃法对咳嗽变异性哮喘(CVA)气虚风动、肺胃气逆证的临床疗效.方法:选取2015年1月至2017年7月中日友好医院呼吸科门诊符合条件的CVA患者110例,随机分为治疗组和对照组,治疗组予益气疏风降胃中药,对照组予沙美特罗替卡松粉吸入剂,疗程均为4周.观察两组治疗前后咳嗽积分及中医证候积分的变化及临床总疗效,随访6个月,观察两组的复发情况.结果:经过4周治疗后,治疗组总有效率(95.45％)优于对照组(77.78％)(P＜0.05),症状积分改善优于对照组(P＜0.01).随访6个月后,对照组复发率(56.3％)显著高于治疗组(10.0％)(P＜0.05).结论:中药益气疏风降胃法治疗CVA效果显著,能有效缓解及控制患者的咳嗽症状,减少咳嗽复发,对其临床治疗有指导意义.

目的尝试用卵清蛋白联合烟熏建立相似度更高的豚鼠CVA模型。方法选取SPF级雌雄各半豚鼠24只,随机分为空白对照组、OVA致敏组与OVA致敏+烟熏组,共3组,每组8只豚鼠。OVA致敏组以卵清蛋白致敏法造模,OVA致敏+烟熏组以卵清蛋白致敏联合烟熏法造模,余方法一致。检测3组受试豚鼠肺顺应性（Cydn）、乙酰甲胆碱激发后气道阻力（RI）、辣椒素激发后咳嗽次数与首次咳嗽时间、肺组织病理及Ashcroft分级表评分指标变化,以评估模型。结果相较于空白对照组,OVA致敏组与OVA致敏+烟熏组Cydn明显下降、RI明显上升、10 min咳嗽次数明显增加、首次咳嗽时间明显提前、肺组织病理变化明显、Ashcroft分级表评分明显上升,以上表现均符合咳嗽变异型哮喘特征。同时,相较于OVA致敏组,OVA致敏+烟熏组在咳嗽症状及RI变化上有更好表现,更符合咳嗽变异型哮喘特征,这可能与降低OVA致敏浓度避免免疫反应过度、烟熏增加咳嗽敏感性密切相关。结论用OVA致敏联合烟熏的方法能建立相似度跟高的咳嗽变异型哮喘豚鼠模型。

从哮喘、慢性阻塞性肺痰病(COPD)、急性肺损伤、肺纤维化4种痰病论述以p38MAPK信号通路为靶点,中医药治疗呼吸系统痰病的研究进展,总结出相关中药方剂、单味中药及中药有效成分基于p38MAPK信号通路治疗呼吸系统痰病的主要作用机制.其主要机理包括改善炎症反应、血管通透性、纤维沉积、氧化活动等方面;p38MAPK信号通路上下游因子,如TGF-β、HSP27、Nrf2、NF-κB、AngⅡ等,也在其中起到了至关重要的作用.