去甲泽拉木醛醇质体凝胶的制备及其体外透皮研究

目的制备去甲泽拉木醛(DMZ)醇质体及其凝胶剂,并考察其制剂性能和体外透皮特性。方法采用注入法制备DMZ醇质体,并对其粒径、包封率、分析方法学及体外释放行为进行研究。采用改良的Franz扩散池进行醇质体凝胶的体外透皮试验。结果 DMZ醇质体外观为淡黄乳状液,平均粒径为(365.2±14.4)nm,包封率为(72.30±2.31)%。醇质体凝胶中DMZ的体外透皮行为符合Higuchi方程(Q=80.198 t1/2-71.641,r=0.986 8),其24 h的累积渗透量是普通凝胶的3.94倍。结论醇质体凝胶可良好地改善DMZ的透皮行为,为雷公藤有效成分的局部透皮制剂的开发提供依据。     

《灵枢》经筋理论探析

十二经筋是附属于十二经脉的筋膜系统,是经络系统的组成部分,其循行分布特点以经脉为纲纪,无脏腑属络;循行方向呈向心性;结、聚、交、合;呈片、面状分布.其病候特点、病理变化分为筋急与筋纵;病位分为经筋所过外周病候与内脏病候;治疗特点有"燔针劫刺",量化刺激标准基于"维筋相交"的交叉取穴法等等,并总结了经筋实质研究进展.     

电针即刻镇痛效应及其对脊髓p-ERK1/2的调控

目的:观察电针对完全弗氏佐剂(CFA)致炎性痛大鼠急性期脊髓背角细胞外信号转导激酶1/2(ERK1/2)磷酸化水平的影响,探讨电针即刻镇痛效应的部分细胞信号转导机制.方法:雄性健康SD大鼠53只,分两批进行实验.第1批实验大鼠23只,全部采用CFA造模,观察CFA致炎对大鼠痛阈的影响,并用免疫组化法检测大鼠患侧脊髓背角p-ERK1/2阳性细胞的表达情况.第2批实验大鼠30只,随机分为空白对照组(N组)、模型对照组(CFA组)和电针治疗组(EA组),每组各10只.CFA组和EA组大鼠采用CFA造模,EA组大鼠造模后5.5h予电针治疗1次.观察电针对CFA大鼠的即刻镇痛效应及其对大鼠脊髓背角p-ERK1/2阳性细胞表达的干预作用.结果:第1批实验大鼠:造模后5h,CFA大鼠痛阈显著降低(P＜0.01),造模后3d、7d、14d 3个时点,CFA大鼠痛阈均显著低于造模前(均P＜0.01);但p-ERK1/2阳性细胞主要集中在造模后5h表达,并于造模后3d恢复正常.第2批实验大鼠:CFA造模成功诱导CFA组和EA组大鼠痛阈降低,与同期N组大鼠相比差异有统计学意义(均P＜0.01).接受1次电针治疗后,EA组大鼠痛阈明显提高(P＜0.01),并显著高于同期CFA组(P＜0.01).造模后6h,CFA组大鼠腰段脊髓背角p-ERK1/2阳性细胞表达增多(P＜0.01),而EA组则明显减少(P＜0.01).结论:抑制炎性痛大鼠腰段脊髓背角ERK1/2活化,可能是电针发挥即刻镇痛效应的关键细胞信号转导机制之一.     

电针对CFA致炎性痛大鼠脊髓ATF-2Thr71位点磷酸化的干预研究

目的:观察电针的镇痛效应及其对脊髓背角活化转录因子2(ATF-2)苏氨酸71(Thr71)位点活化的干预作用。方法:实验分为空白对照组(N组)、模型对照组(CFA组)和电针治疗组(EA组)。CFA组和EA组通过足内注射弗氏完全佐剂(CFA)建立大鼠炎性痛模型,EA组于造模后1d选取双侧"足三里"、"昆仑"穴进行电针治疗。分别观察造模前、造模后1、3和14d的足缩腿阈(PWTs),及患侧脊髓背角磷酸化ATF-2(p-ATF-2)(Thr71)阳性细胞数。结果:与N组相比,于造模后各时段,CFA组大鼠PWTs显著降低(P0.05),p-ATF-2(Thr71)阳性细胞数增多(P0.01);造模后3、14d时,EA组大鼠PWTs显著高于同期CFA组(P0.01),而p-ATF-2(Thr71)阳性细胞数则明显少于同期CFA组(P0.05)。结论:电针抗炎性痛作用与抑制脊髓背角ATF-2(Thr71)的磷酸化密切相关。     

电针治疗CIA大鼠慢性炎症及对COX-2的选择性抑制作用

[目的]探讨电针的抗慢性炎症作用和对环氧合酶的干预作用,明确电针抗慢性炎症疼痛的部分关键机理及优势。[方法]采用大鼠胶原诱导性关节炎(CIA)为慢性炎症动物模型,以关节炎指数、炎症局部肿胀容积和PGE2含量等为指标,观察电针刺激大鼠相当于“足三里”穴对炎症大鼠的治疗作用,并与传统非甾体抗炎药消炎痛(Indomethacin)、选择性COX-2抑制剂罗非昔布(Rofecoxib)治疗进行疗效比较。在此基础上,采用逆转录聚合酶链反应(RT-PCR)检测CIA模型大鼠及各治疗组大鼠膝关节滑膜组织和胃粘膜中COX-1、COX-2mRNA表达变化。[结果]电针可有效抑制CIA大鼠关节炎指数、足跖肿胀度以及血清和炎症局部组织中PGE2含量,控制病情的进一步发展。电针对COX-2mRNA表达有选择性抑制作用,对胃粘膜COX-1表达无影响;消炎痛和罗非昔布在抗炎过程中,既抑制关节滑膜组织中COX-2mRNA表达,对胃粘膜COX-1表达也进行抑制。[结论]电针对胶原性关节炎大鼠慢性炎症具有良好的抗炎效应,其抗慢性炎症作用途径可能通过对COX-2进行选择性抑制;电针抗炎无胃肠道副反应。     

Electroacupuncture Attenuates Spinal Nerve Ligation-Induced Microglial Activation Mediated by p38 Mitogen-Activated Protein Kinase

Objective

To investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia.

Methods

There were two experiments. The experiment 1: 40 male Sprague-Dawley (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation (SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide (DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above.

Results

SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42 (P<0.01 or P<0.05).

Conclusions

The central mechanism of EA-induced anti-hyperalgesia may be partially associated with the reduced expression of p-p38 MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain. Therefore, EA may be a new complementary and alternative therapy for neuropathic pain.

     

《伤寒论》太阳篇火逆证浅析

火法系指烧针、灸疗、薰法、熨法等与火热有关的治疗方法。火法主要适用于寒湿痹证,一般不适用于太阳病,尤其对体内素有郁热或素有津伤者不适合,一旦误用多会致生严重变证。火力虽微,内攻有力,或使气血失其常度,或焦骨伤筋,或逼迫心阳浮越。     

电针足三里、三阴交穴治疗大鼠胶原性关节炎及其部分血液流变学机制

[目的]观察电针“足三里”、“三阴交”穴对胶原性关节炎（Collagen-induced Arthritis,CIA）大鼠的治疗作用及其部分血液流变学机制。[方法]36只Wistar大鼠随机分为空白对照组、模型对照组和电针治疗组,模型对照组和电针治疗组大鼠采用牛Ⅱ型胶原在大鼠背部正中线作多点皮内注射诱发CIA模型,选取“足三里”、“三阴交”穴进行电针治疗,观察CIA大鼠足跖肿胀度、痛阈和踝关节的病理变化,检测全血粘度和红细胞聚集指数观察血液流变学变化。[结果]电针“足三里”、“三阴交”穴可显著减少CIA大鼠关节炎肢体累及数、抑制足跖肿胀、提高痛阈、减少踝关节病理损伤;电针治疗组大鼠全血粘度低切下降显著（P〈0．01）,红细胞聚集指数与模型对照组大鼠比较也有明显下降（P〈0．05）。[结论]电针“足三里”、“三阴交”对大鼠胶原性关节炎具有较好的治疗作用,其机制可能与改善大鼠的血液流变学指标有关。     

燔针劫刺治疗中风后痉挛性瘫痪的思路探讨

中风痉挛性瘫痪一直是困扰广大医疗工作者的难题,笔者通过以往临床经验和大量文献查阅,为燔针劫刺治疗中风后痉挛性瘫痪提供有力的理论依据,为进一步临床研究的开展建立良好的基础。     

p38MAPK通路参与炎性痛及电针干预的可能性

丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)是细胞内重要的信号传导系统之一.p38MAPK是丝裂原活化蛋白激酶的重要组成部分之一,在炎症性疼痛的发生发展过程中发挥着重要作用,已有大量资料表明电针具有较好的抗炎镇痛作用,同时有研究发现电针具有调节p38MAPK活化的作用,所以电针在炎性痛疾病中对p38MAPK通路干预存在可能性.