从慢性心理应激损伤与细胞自噬角度探讨肝主疏泄的功能实质

自噬是细胞特有的保护机制。细胞自噬通过清除细胞内异常折叠蛋白及受损细胞器等,以维持细胞正常的物质代谢与生理功能,这与中医学的肝主疏泄,调节机体正常气机,以维持人体正常的代谢及生命活动具有相似的内涵。慢性心理应激损伤属于中医学情志内伤病因范畴,其发病机制与肝的疏泄功能失常密切相关。以慢性心理应激损伤为切入点,从细胞自噬的角度探讨肝主疏泄的功能实质,对于深入挖掘中医学肝脏象理论的内涵具有重要意义。     

肝主疏泄与心理应激的理论探讨

“疏泄”一词来源于《内经》 ,朱丹溪最早提出“司疏泄者肝也” ,其时是指肝具有疏泄肾精的功能。中医理论认为 ,肝主疏泄实际上包括肝脏多种功能 ,如调节气机、促进脾胃运化、调畅情志、疏泄肾精等等。而肝主疏泄功能中最为主要的是调节气机 ,气机调畅则气血津液运行正常 ,脏腑功能得以正常发挥。从中医角度而言 ,任何形式的应激主要是影响机体正常的气机。由此可见 ,肝主疏泄功能在机体心理应激反应中起着决定性作用 ,肝是机体调节心理应激反应的核心。下面就从心理应激角度探讨肝主疏泄的生理机制及其临床意义。1　肝主疏泄的心理应激机…     

肝主疏泄的意义及其临床应用

<正> 肝主疏泄,是肝脏的主要生理功能之一。肝在人体内担负着藏血和调节人体血液分布,疏通一身之气机,与其它脏器共同维持正常生理活动,这些都与肝的疏泄功能有密切关系。笔者结合临床体会,将肝主疏泄的生理病理、临证治要作以简述,以供参考。肝主疏泄的含义肝主疏泄是指肝脏具有调节精神、情志活动,疏通气血,化导瘀阻,宣泄清浊的作用。     

从心理应激理论探讨中医肝主疏泄功能的研究思考

基于中医基础理论及其相关的研究进展,结合现代心理应激理论,探讨中医肝主疏泄功能的相关理论,并提出相关研究的思考。通过对心理应激理论与肝主疏泄功能及其近年相关的研究进展的整理归纳,认为心理应激理论与中医的肝主疏泄功能是密切相关的,从中医角度来看,中医的肝主疏泄功能在机体调节心理应机中起到了决定性的作用,从而对今后从心理应激理论探讨中医肝主疏泄功能的研究提出了思考与展望。     

肝主疏泄新解

传统医学认为"肝主疏泄"功能的正常发挥依赖于五脏的协同作用,而缺乏解剖学与生理学分析,现代医学认为"肝主疏泄"的生理学机制与肝窦内皮功能、金属硫蛋白、神经-内分泌-免疫系统等有关,以此为基础展开论述,通过全新视角诠释"肝主疏泄"的含义。     

肝主疏泄调畅情志的发病机制探究

肝主疏泄功能与情志活动密切相关,调畅情志是肝主疏泄的一个重要功能。情志以血(精)为本,以气为用,情志异常对机体的影响,主要表现为干扰正常的气血运行。中医所述情志异常属于病理性心理应激反应的范畴,肝主疏泄可调节心理应激反应,因此心理应激反应也成为研究肝主疏泄、调畅情志功能的中枢神经生物学机制的一个很好的切入点。现结合肝主疏泄调畅情志的中医理论和现代医学神经-内分泌-免疫调节和心理应激理论,对肝主疏泄调畅情志的发病机制进行探讨。     

当代肝主疏泄理论框架构建分析

为厘清当代“肝主疏泄”的理论框架和构建方式,作者通过比较各个版本的全国统编中医基础理论教材,分析肝主疏泄理论框架的构建过程。认为,“疏肝解郁”等治法的广泛应用是当代“肝主疏泄”的临床基础,“西医知识”和“命门学说”是重构当代“肝主疏泄”的主要知识基础,当代阴阳五行学说及气机理论是当代“肝主疏泄”的构建方法。从理论框架的角度分析,肝主疏泄是当代学者,采用当代阴阳五行学说,整合古代肝脏理论、当代肝脏疾病诊治知识、西医学相关知识以及当代哲学思想,创造性构建的一个新理论。当代“肝主疏泄”理论框架构架分析从理论构建的角度证明了中医理论的发展需要采用新方法分析新知识、新临床经验,创造性地构建新理论。这无论是对肝脏象理论、中医脏象理论的研究、现代肝脏象理论、中医脏象理论和中医理论的构建都有积极的意义。     

从心理应激理论研究中医肝主疏泄脏象本质

将现代心理应激理论引入中医脏象学说的研究中,结合中医基础理论及相关研究进展,着重探讨了中医肝主疏泄功能的心理应激机制。认为肝主疏泄的功能在机体心理应激中起决定性作用;从中医理论而言,肝是机体调节心理应激反应的核心。同时对今后相关研究的思路及方法进行了初步探讨。     

肝主疏泄机理探析

解剖学中的肝脏是肝主疏泄形成的形态学基础。通过古代的解剖观察,古人认识了肝的名称、大体解剖部位和大体解剖形态,在对肝脏形态学观察的基础上,认识了肝主藏血的生理功能。中医学的整体观念是表象综合、援物类比肝主疏泄的主要依据,人与自然界的整体统一观以及其在自然环境的影响下所表现出来的宏观的生理、病理现象和对治疗的反证,是认识肝主疏泄功能的主要基础。     

生命早期应激下肝调畅情志功能中枢改变探讨＊

生命早期应激是导致肝调畅情志功能变化的重要病因，情志内伤肝失疏泄病证过程又在生命早期应激状态下得到更好地体现。鉴于两者的紧密相关性，病证结合开展生命早期应激反应状态下的肝失疏泄情志失调功能研究，结果表明，早期应激下肝调畅情志功能中枢改变与中缝背核、海马和前额叶皮质等部位单胺类神经递质相关，尤以5-HT系统改变密切。调肝经典方剂四逆散及其加味可以显著改善生命早期应激状态大鼠的抑郁表现，与中缝背核5-HT_1AR、5-HTT、CaSR、BDNF等蛋白表达、海马5-HT_1AR-CREB-BDNF信号通路变化、改善海马和皮质Nissl体损伤有关。针对生命早期神经元生长及突触形成特点，早期（特别是青少期）应激状态下5-HT系统改变可作为观测肝主疏泄调畅情志功能变化的核心靶点与通路。早期应激与成年后应激诱导的联合研究应成为未来的重要方向。     

金属硫蛋白在铜绿治疗小鼠实验性肝癌中的作用

目的：研究金属硫蛋白（ｍｅｔａｌｌｏｔｈｉｏｎｅｉｎ，ＭＴ）在铜绿治疗实验性小鼠肝癌（Ｈ２２）过程中所起的作用。方法：采用原子吸收法、银饱和法、组织化学法同步观察了肝脏及肿瘤组织中铜元素与ＭＴ的含量及分布规律。结果：（１）治疗组肝组织内铜及ＭＴ含量均明显高于模型组；（２）治疗组肿瘤组织中铜含量明显高于模型组，而ＭＴ含量显著低于模型组；（３）组织化学检测可见治疗组肝细胞浆和核内铜元素及ＭＴ同时存在。     

电针调节松果体褪黑激素作用的观察

目的:探索电针调节松果体褪黑激素(MT)的作用。方法:将52只清洁级SD雄性大鼠随机分为假手术组(sham,8只)、模型组(model,8只)、电针组(EA,8只)、褪黑激素组(MT,3.2mg/kg,8只)、电针加MT组(EA+MT,8只)、电针加MT阻滞剂Luzindole组(EA+L,每只1mg/100μl,6只)、电针加MAPK阻滞剂PD98059组(EA+P,每只1mg/100μl,6只)。用改良Longa血管内线栓法制成脑缺血、缺氧再灌注模型。用连续波、频率3Hz,强度1～3mA等刺激参数电针"百会"大椎"30min。用高效液相色谱技术测定各组大鼠脑松果体内MT的含量;依据Kuluz神经缺陷三级评分标准和Julio氏神经行为学评分法对大鼠神经行为进行评分;用免疫组化法显示脑纹状体内Bax/Bcl-2基因蛋白表达。结果:模型组Bcl-2免疫反应阳性的细胞数、神经行为学评分明显低于假手术组和各治疗组(P<0.01),Bax免疫反应阳性的细胞数、Bax/Bcl-2显著高于假手术组和各电针组及MT组(P<0.001);电针大鼠"百会"大椎"可使脑松果体内MT浓度大量增加(P<0.01),神经行为学评分显著改善(P<0.01),使脑纹状体组织内Bcl-2基因表达的细胞数明显增加(P<0.001),降低Bax/Bcl-2(P<0.001)。EA+L组与EA+P组之间的MT和行为学评分,及MT组和EA+MT组间Bax、Bcl-2阳性细胞数及Bax/Bcl-2的差异均无显著性意义(P>0.05)。结论:电针可逆转由于脑缺血、缺氧再灌注所造成的脂质过氧化及自由基连锁反应,达到抗氧应激和脑保护作用,其中脑松果体内MT分泌增加及释放可能起着至关重要的作用。     

Melatonin might be one possible medium of electroacupuncture anti-seizures

To explore the alteration of melatonin (MT) levels in pineal, hippocampus and serum during seizure crises and electroacupuncture (EA) anti-seizures, we established a rat seizure model by microinjecting benzylpenicillin into hippocampus. EA was performed on "Fengu" (DU 16) and "Jinsuo" (DU 8) acupoints in rats. Electroencephalogram (EEG) of rats was recorded and the relative power (RP) of 1 approximately 30 HZ band of EEG was analyzed. A capillary electrophoresis-electrochemical detection method was used to determine MT contents. Our results indicated that MT level was elevated in pineal and hippocampus, and first had no change then significantly evaluated in serum during seizure crisis. The elevation of MT level was greatly potentiated with 30 min EA treatment (P<0.05). Meanwhile, the degree of seizures and the increases of EEG RP induced by seizures were significantly reduced (P<0.05). Because MT was considered as an antistressor and a natural downregulator of epileptiform activity, we postulate that the elevation in MT level during seizures may be one endogenous mechanism that counteracts convulsions and seizure-induced stress. A further elevation of MT levels with EA treatment suggests that MT might be one of the possible mediums of EA anti-seizures.     

褪黑素和电针对创伤大鼠免疫功能的影响

以往的研究表明 ,创伤应激能广泛抑制机体的免疫功能。本实验室研究了褪黑素和电针对创伤大鼠自然杀伤细胞活性、脾淋巴细胞增殖反应和白细胞介素 2诱生活性的影响。结果发现腹腔注射褪黑素 5ｍｇ/ｋｇ可明显恢复术后 2 4ｈｒ大鼠低水平的自然杀伤细胞活性 (Ｐ <0 .0 5) ,并且被抑制的淋巴细胞增殖功能和白细胞介素 2的诱生活性有所逆转 (Ｐ <0 .0 5,Ｐ <0 .0 5)。电针刺激“足三里”(ＳＴ 36 )和“阑尾”(Ｅｘｔｒａ 37)穴也能够明显改善创伤诱导的免疫抑制。褪黑素和电针结合能进一步调节抑制的免疫功能 ,自然杀伤细胞活性、淋巴细胞增殖…     

Antifibrotic activity of Taraxacum officinale root in carbon tetrachloride-induced liver damage in mice

Aim of the study

Dandelion (Taraxacum officinale) has been traditionally used in the treatment of various liver disorders. The present study was aimed to assess the efficacy of dandelion root water–ethanol extract (DWE) in carbon tetrachloride (CCl₄)-induced hepatic fibrosis.

Materials and Methods

The mice were treated with CCl₄ dissolved in olive oil (20%, v/v, 2 ml/kg) intraperitoneally (i.p.), twice a week for 4 weeks. DWE was administered i.p. once daily for next 10 days, in doses of 200 and 600 mg/kg of body weight. The degree of hepatic fibrosis was determined by hydroxyproline content and Mallory trichrome staining. Oxidative stress was determined by measuring hepatic superoxide dismutase (Cu/Zn SOD) activity. The expression and specific tissue distribution of glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA), and metallothionein (MT) I/II in the liver were determined by immunohistochemistry.

Results

Hepatic Cu/Zn SOD activity has been decreased in intoxicated mice and normalized in DWE treated groups. MT I/II immunopositivity was strongly reduced in the CCl₄ group. DWE treatment successfully decreased hepatic fibrinous deposits, restored histological architecture, and modulate the expression of GFAP and α-SMA. Concomitantly, MT I/II expression increased in the DWE treated groups.

Conclusions

Our results suggest the therapeutic effect of DWE on CCl₄-induced liver fibrosis by the inactivation of hepatic stellate cells and the enhancement of hepatic regenerative capabilities. The present results provide scientific evidence to substantiate the traditional use of Taraxacum officinale root in hepatic disorders.     

Sucrose preference is restored by electro-acupuncture combined with chlorimipramine in the depression-model rats

The present study was to investigate the effect of electroacupuncture (EA) combined with chlorimipramine on the sucrose preference of depressive rats induced by chronic mild stress (CMS). Rats were exposed chronically (1st - 4th week) to a variety of mild unpredictable stresses. The tricyclic antidepressant chlorimipramine and EA were administrated on these depressive rats for 6 weeks (5th - 11th week). EA was applied at points of "Bai-Hui" (Du 20) and "An-Mian" (EX 17) (right side), by EA apparatus (Model 6805-2, Shanghai). Dense (60Hz/5sec)-sparse (4Hz/2.5sec) frequency of the wave was selected and the current intensity (< or = 1mA) was adjusted to provoke slight twitches of the rat's ear. The preference for 1% sucrose solution and the immobility time in the forced swimming test were measured as the symptoms of anhedonia and depressed mood, which were central features of major depression. The preference for 1% sucrose solution was reduced by CMS, but could be restored to normal level after 6 weeks treatment with chlorimipramine at 5mg/kg or EA combined with chlorimipramine at 2.5mg/kg. In the forced swimming test, the immobility time of depressive rats was decreased in both groups. However, the preference for sucrose and the immobility time in the depressive rats were not significantly changed by the treatment with only EA or chlorimipramine at 2.5 mg/kg. The results suggested that EA could potentiate the antidepressant effect of chlorimipramine in low dose, and EA combined with antidepressant might be a better method in treating depression.     

平疏结合法治疗郁证之机理初探

分析郁证的病因病机,总结在多年临床实践中发展出的疏通气机与平肝潜阳相结合的治法,从肝脏的疏泄功能、郁证的临床分型、临床疗效三种角度阐述采用平疏结合治法的机理和作用,就郁证临床七种证型逐一说明平疏结合之利弊,从理论上探讨其可行性,最后通过经验病例加以检验。实践与理论均说明该法具有一定的可取之处,不失为当今中医临床治疗郁证的一种新思路。     

唐启盛教授治疗抑郁障碍的学术经验

唐启盛教授认为抑郁障碍与中医的"郁病"关系密切,情志之郁与气血痰食火等病机之郁有所区别,初起多为情志不遂而肝气郁结、痰气郁结,久则暗耗肾精,以致肾精亏虚,水不生木,因此提出"肾虚肝郁"的病机。通过数据挖掘,分析了抑郁障碍的中医证候规律,发现肾虚肝郁是抑郁障碍最常见的证候类型。治疗上运用益肾调气法,创立颐脑解郁方,用以治疗抑郁障碍,疗效显著。     

丙氧锗二酸对顺铂毒性的保护作用及其对抗癌效果的影响

 本文研究了丙氧锗二酸（Ge－132）对顺铂毒性及抗癌效果的影响，并对其保护作用与金属硫蛋白（metallothionein，MT）的关系进行了探讨。结果表明Ge－132对顺铂引起的肾脏、血液和致死的毒性具有明显的保护作用。其效果优于次硝酸秘、亚硒醚钠以及氧化锗；Ge－132无诱导MT的作用，经体内抑瘤实验及体外细胞毒性实验表明，Ge－132对顺铂的抑瘤作用无统计学意义的影响。