强啡肽在大鼠脊髓内的强烈镇痛作用

本文首次报告,将强啡肽注入大鼠脊髓蛛网膜下腔有强烈而持久的镇痛作用。用辐射热甩尾阈升高幅度和镇痛时程为指标,强啡肽镇痛作用在2.3—18.6毫微克分子范围内呈明确的剂量效应关系。若以等克分子计算,较吗啡的镇痛作用强6—10倍,较另一μ型阿片受体激动剂morphiceptin强65—100倍。应用强啡肽抗血清中提出的免疫球蛋白G可以完全对抗强啡肽的镇痛作用。纳洛酮也可对抗强啡肽镇痛,但作用慢而弱。在急性吗啡耐受的大鼠,强啡呔的镇痛作用依然存在,说明两者不产生交叉耐受。多方面的资料表明,强啡肽在脊髓的镇痛作用可能是通过k型阿片受体而实现的。与脊髓内注射不同,脑室内注射强啡肽并无镇痛作用。     

家兔脑内微量注射纳洛酮对吗啡和针刺镇痛的影响

已有许多工作证明,中枢神经系统中的内源性鸦片样物质(OLS)与针刺镇痛有关,但其确切作用部位迄末阐明。本工作用脑内微量注射鸦片受体阻断剂的方法证明,家兔脑内的伏核、杏仁核、缰核和导水管周围灰质,是针刺镇痛时OLS作用的关键部位,这些脑区在吗啡镇痛中也发挥重要作用。     

ACCELERATED SYNTHESIS AND RELEASE OF ANGIOTENSIN II IN THE RAT BRAIN DURING ELECTROACUPUNCTURE TOLERANCE

Behaviouzal studies suggested that cerebral angiotensin Ⅱ (AⅡ) plays an important role in the development of tolerance to electroacupuncture (EA) analgesia. Observations made in this study revealed an increase in AⅡ immunoreactivity (AⅡ-it) in both CSF and brain as well as an increase in the cerebral content of AⅠ-ir in rats rendered tolerant to EA. The extracts of brain from rats receiving EA for 1h and 3h were subjected to gel filtration and the elution profile was compared with that of normal brain extract. There was a marked right shift of the AⅡ peak from the large molecule precursor to the small molecule AⅡ-ir.The latter peak showed the same retention time in HPLC system as that of AⅡ. The results suggest that the acceleration of the synthesis and release of AⅡ during s Iong-term EA stimulation might constitute one of the mechanisms for EA tolerance.     

中枢5-羟色胺在电针镇痛耐受中的作用

给大鼠多次电针,电针镇痛效果逐渐减弱,而产生电针镇痛耐受,并与吗啡镇痛产生交叉耐受。脑室注射5-羟色胺(5-HT)的前体可以翻转电针镇痛耐受。测定电针镇痛耐受的动物脑内5-HT含量和更新率并不降低,5-HT受体的最大结合力也未见下降。多方面的资料表明,机体对内源性释放的5-HT发生耐受,可能是电针镇痛耐受的一个重要原因。     

血管紧张素Ⅱ和DPDPE对NG108-15细胞c-fos的影响

本文应用免疫组化,免疫沉淀和点杂交方法研究了血管紧张素Ⅱ(angiotensinⅡ,AⅡ)和δ阿片受体激动剂DPDPE对NG108-15细胞原癌基因c-fos表达的影响。结果表明,10~(-7)mol/L AⅡ可诱导NG108-15细胞c-fos的表达,显著增加Fos样免疫活性(FLI),Fos蛋白含量及c-fos mRNA的表达,这些作用能被特异性AⅡ受体拮抗剂Saralasin拮抗。10~(-7)mol/L DPDPE也能加速NG108-15细胞c-fos的表达,该效应可被阿片受体阻断剂纳洛酮阻断。在等摩尔浓度下,AⅡ的作用显著大于DPDPE。将AⅡ和DPDPE同时作用于细胞,c-fos被诱导表达的水平等于或反而低于AⅡ单独作用时的水平。以上结果首次报道,在神经母细胞和胶质细胞杂交株NG108-15细胞上,激活AⅡ和DPDPE受体均可诱导c-fos原癌基因的表达,而两者同时作用时则有相互抑制效应。     

中枢5-羟色胺在针刺镇痛中的作用

本文在大鼠辐射热一甩尾针刺镇痛动物模型上对中枢5-羟色胺(5-HT)在针刺镇痛中的作用进行了进一步的研究.证明电针可引起中枢5-HT的功能活动加强,后者是实现针刺镇痛的重要基础.     

电针耐受时大鼠脑内血管紧张素Ⅱ的生成和释放加速

本文研究表明,电针耐受时大鼠脑脊液中All样免疫活性物质(AII-ir)的浓度增高,脑内AII-ir和AI-ir的含量也明显增高。并观察到,电针1和3h的大鼠脑提取物经分子筛层析,发现大分子前体AII-ir峰明显右移,并出现小分子AII-ir峰。经高效液相层析鉴定,电针后出现的小分子AII-ir峰与AII标准品具有相同的保留时间。结果表明,长时间电针加速了脑内AII的生成和释放,这可能是AII参与电针耐受的机理之一。     

DYNORPHIN: POTENT ANALGESIC EFFECT IN SPINAL CORD OF THE RAT

Evidences are presented to show a strong and long-lasting analgesic effect after injec-tion of dynorphin into the subarachnoid space of the spinal cord in the rat. Taking theamplitude and time course of the increase of tail flick latency as the indices of analgesia,dynorphin elicited dose-dependent analgesic effect in the range of 2.3--18.6 nmol. Calcu-lating on a molar basis dynorphin was 6--10 times more potent than morphine and 65--100 times more potent than morphiceptin, another mu opiate receptor agonist. Dynorphinanalgesia was completely reversed by intrathecal injection of anti-dynorphin IgG and par-tially reversed by naloxone. Acute tolerance to morphine analgesia did not affect the occu-rance of dynorphin analgesia, indicating the absence of cross tolerance between morphineand dynorphin. Evidence from different lines of approach suggests that dynorphin may bindwith kappa opiate receptors in the spinal cord to exert its analgesic effect     

THE IMPLICATION OF CENTRAL SEROTONIN IN ELECTRO-ACUPUNCTURE TOLE

Electro-acupuncture (EA) applied to both legs for 30min raised the tail flick latencyof the rat significantly. This effect of EA analgesia became attenuated and finally disap-peared after repeated EA stimulations, which was termed EA tolerance. EA tolerance and itscross tolerance to morphine analgesia were found to be partially reversed by intracerebro-ventricular injection of 5-hydroxytryptophan (5-HTP), the precursor of 5-hydroxytryptamine(5-HT). However, there was no depletion in cerebral 5-HT, nor was there decrease ofthe number of 5-HT receptors in the brain of the EA tolerant animals. Results obtainedfrom different lines of analysis point to the conclusion that development of tolerance toprofoundly released 5-HT during prolonged EA stimulation may constitute one of themechanisms for EA tolerance.     

脊髓蛛网膜下腔注射去甲肾上腺素的降压效应及其与强啡肽的关系

大鼠脊髓蛛网膜下腔注射去甲肾上腺素引起中枢性降压效应,此效应可被a受体阻断剂酚妥拉明、哌唑嗪或育亨宾所拮抗,但不受β阻断剂心得安、Metoprolol或Butoxamine的影响。强啡肽抗体或大剂量纳洛酮也可对抗去甲肾上腺素或a受体激动剂可乐宁的心血管抑制效应;而β-内啡肽、甲啡肽与亮啡肽抗体以及小剂量纳洛酮均无拮抗作用。蛛网膜下腔注射强啡肽可引起与剂量相关的降压效应。以上结果提示,脊髓蛛网膜下腔注射去甲肾上腺素的降压效应与脊髓内a受体的激活以及内源性强啡肽的释放有关。