电针夹脊穴在佐剂性关节炎大鼠镇痛过程中磷酸化p38丝裂原活化蛋白激酶的变化及作用

目的:观察电针夹脊穴对佐剂性关节炎大鼠背根神经节(dorsalrootganglion,DRG)内磷酸化p38MAPK表达的影响,从信号转导的角度研究电针镇痛的机制。方法:以完全福氏佐剂(CFA)佐剂性关节炎大鼠为疼痛模型,采用免疫组化技术,分别检测空白对照组、模型组、及电针治疗组SD大鼠DGG内磷酸化p38丝裂原活化蛋白激酶(mitogen-activatedproteinki-nase,MAPK)表达特征。结果:与空白对照组犤(7.65±0.72)s犦相比,造模后24,48h及7d后,模型组大鼠痛阈下降分别为(6.67±0.59),(6.53±0.73),(6.64±0.76)s,同时DRG内p38MAPK磷酸化明显增多(P<0.05),尤以48h后增加明显;电针治疗组大鼠在电针夹脊穴治疗后,24,48h及7d后痛阈检测发现其痛阈回升,分别为(7.31±0.79),(7.42±0.93),和(7.44±0.89)s,DRG内p38MAPK磷酸化水平下降(P<0.05)。结论:p38MAPK可能为电针镇痛中一个重要的信号转导分子,其磷酸化在疼痛及电针镇痛过程中其重要作用。     

电针夹背穴在佐剂性关节炎大鼠镇痛过程中磷酸化p38丝裂原活化蛋白激酶电针的变化及作用

目的观察电针夹脊穴对佐剂性关节炎大鼠背根神经节(dorsal root ganglion,DRG)内磷酸化 p38MAPK表达的影响,从信号转导的角度研究电针镇痛的机制.方法以完全福氏佐剂(CFA)佐剂性关节炎大鼠为疼痛模型,采用免疫组化技术,分别检测空白对照组、模型组、及电针治疗组 SD大鼠 DGG内磷酸化 p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)表达特征.结果与空白对照组 [(7.65± 0.72) s]相比,造模后 24,48 h及 7 d后,模型组大鼠痛阈下降分别为 (6.67± 0.59),(6.53± 0.73), (6.64± 0.76) s,同时 DRG内 p38MAPK磷酸化明显增多(P< 0.05),尤以 48 h后增加明显;电针治疗组大鼠在电针夹脊穴治疗后, 24, 48 h及 7 d后痛阈检测发现其痛阈回升,分别为 (7.31± 0.79),(7.42± 0.93),和 (7.44± 0.89) s , DRG内 p38MAPK磷酸化水平下降(P< 0.05).结论 p38MAPK可能为电针镇痛中一个重要的信号转导分子,其磷酸化在疼痛及电针镇痛过程中其重要作用.     

A型肉毒毒素对关节炎疼痛大鼠脊髓小胶质细胞活化及肿瘤坏死因子-α表达的影响

目的 观察A型肉毒毒素（BTX-A）注射对佐剂性关节炎大鼠疼痛行为及脊髓小胶质细胞激活、肿瘤坏死因子-α(TNF-α)表达的影响,并探讨BTX-A治疗佐剂性关节炎疼痛的可能机制。 方法 采用随机数字表法将60只清洁级雄性SD大鼠分为假手术组、完全弗氏佐剂组（模型组）和BTX-A组,每组20只大鼠。除假手术组外,其余2组均于左后肢踝关节腔注射50 μl CFA建立佐剂性关节炎疼痛模型,假手术组大鼠关节腔内注射50 μl生理盐水作为对照。造模成功后假手术组和模型组大鼠左后肢踝关节腔注射20 μl生理盐水,BTX-A组大鼠注射20 μl 5 U BTX-A。于造模前1天、造模后第1,3,7,14,21天及给药后第1,3,7,14天对各组大鼠机械痛阈和热痛阈进行测定;并于测试后取出相应时间点脊髓组织,采用免疫蛋白印迹法、免疫荧光染色法检测离子钙接头蛋白(IBA-1)表达及IBA-1免疫阳性细胞(IBA-1-IR)数量;另采用ELISA法、实时荧光定量逆转录-聚合酶链反应（RT-PCR）检测脊髓水平TNF-α蛋白及TNF-α mRNA表达情况。 结果 与模型组比较,BTX-A组踝关节腔注射BTX-A后第3天时其机械痛撤足阈值及热痛阈潜伏期均明显增加,直到注射后第14天时差异均具有统计学意义(P<0.01);脊髓水平IBA-1蛋白表达显著降低,IBA-1免疫阳性细胞数量明显下调（P<0.01）;TNF-α蛋白及TNF-α mRNA表达均明显降低(P<0.05)。 结论 BTX-A可减轻 CFA诱导的关节炎疼痛,其镇痛机制可能与抑制脊髓小胶质细胞活化及TNF-α释放有关。     

大麻素CB1受体和纹状体多巴胺D2受体参与电针镇痛机制

目的:研究大麻素CB1受体和多巴胺D2受体是否参与单次或反复电针镇痛机制。方法:以完全弗氏佐剂(complete Freund's adjuvant,CFA)造成佐剂性关节炎大鼠模型,分别对单次及反复电针后的大鼠进行痛阈和纹状体D2受体mRNA表达水平检测。同时用CB1受体拮抗剂或激动剂干预。结果:①单次和反复电针后痛阈均升高,且关节炎痛+电针+拮抗剂组的镇痛效果弱于关节炎痛+电针组(P<0.01);关节炎痛+激动剂组与关节炎痛+电针组镇痛效果比较,差异无统计学意义。②无论是单次或反复电针,关节炎痛+电针+拮抗剂组大鼠纹状体D2受体mRNA表达水平显著低于电针组(P<0.01)。③在反复电针观察组中,关节炎痛+激动剂组大鼠纹状体D2受体mRNA表达水平与关节炎痛组相比,差异无统计学意义,显著低于关节炎痛+电针组(P<0.01)。结论:在本实验条件下,单次和反复电针产生的镇痛作用可能部分通过大麻素受体CB1介导,纹状体D2受体可能也参与其中。     

隔三七饼灸治疗兔佐剂性膝关节炎实验研究

目的:探讨隔三七饼灸对佐剂性膝骨性关节炎(KOA)兔软骨细胞及血清、关节滑液和关节软骨中基质金属蛋白酶-3(MMP-3)、诱导型一氧化氮合成酶(iNOS)的影响。方法:健康青紫蓝家兔50只,随机选取8只作为空白组(A组),余42只采用1.6%木瓜蛋白酶诱导的兔佐剂性膝关节炎模型,随机分为模型组(B组)、隔三七饼灸组(C组)、双氯芬酸钠灌胃组(D组)。对C组、D组2组分别进行治疗,隔天1次,10次1个疗程,共治疗2个疗程。在治疗前、第1个疗程末、第2疗程末分别检测各组兔血清、关节滑液和关节软骨中MMP-3、iNOS的含量。第2疗程结束后,各组取患侧关节软骨制作病理切片,并在光镜下观察其病理变化。结果:造模结束2周后,与空白组比较,B组、C组、D组中MMP-3、iNOS含量均有显著性升高,P<0.01;治疗10次后,C组、D组均有明显降低,P<0.05;治疗20次后,与模型组比较,C组、D组均显著降低,P<0.01;病理切片显示,隔三七饼灸能明显减轻软骨损伤,抑制细胞增生。结论:隔三七饼灸能有效降低佐剂性膝关节炎模型兔血清、关节滑液和关节软骨中MMP-3、iNOS的含量,减轻关节软骨损伤程度,是治疗膝关节炎的有效方法。     

电针镇痛与神经病理性疼痛大鼠脊髓大麻素2受体表达

目的:观察电针对慢性坐骨神经缩窄性损伤(CCI)模型大鼠的镇痛效果及脊髓背角、背根神经节大麻素2受体(CB2)表达,探讨电针镇痛可能的机制.方法:健康SD雄性大鼠共40只,随机分为CCI假手术组(n=10);CCI对照组(n=10);CCI假电针组(n=10);CCI电针组(n=10).所有大鼠均在术前、术后第9、11、13、15、16d进行机械性痛阈测定;各组大鼠于术后第16d,采用Western blot法测定脊髓背角、背根神经节CB2受体蛋白表达.结果:CCI对照组、CCI假电针组和CCI电针组大鼠在治疗前机械性痛阈较术前明显下降,与同一时间段CCI假手术组大鼠比较差异有统计学意义(P＜0.05).治疗后6d,CCI电针组机械性痛阈较治疗前有一定改善(P＜0.05);CCI电针组与CCI假电针组和CCI对照组比较脊髓背角、背根神经节CB2的表达有下降的趋势,但差异无统计学意义(P＞0.05).结论:本研究观察到电针治疗能够在一定程度上改善CCI模型大鼠的机械性痛阈,起到一定的镇痛效果,但是本研究结果未能提示其镇痛机制有脊髓背角、背根神经节CB2的参与.     

完全弗氏佐剂致痛大鼠脊髓中谷氨酸转运蛋白表达的变化

目的：观察完全弗氏佐剂（CFA）致痛大鼠脊髓中谷氨酸转运蛋白表达的变化规律.方法：取8只大鼠足底注射CFA 100μL建立疼痛模型，观察大鼠致痛后10 d内热痛阈及触诱发痛阈的变化.另取20只大鼠经足底注射CFA 100 μL建立疼痛模型后观察大鼠脊髓内谷氨酸转运蛋白表达的变化.结果：CFA致痛后大鼠痛阈均显著低于致痛前（P＜0.01），其中以致痛后3 d内痛阈降低最为显著，以后痛阈逐渐升高，10 d后痛阈恢复至基础值的70%左右.免疫组化染色可见在正常未致痛时，大鼠脊髓中均有两种谷氨酸转运蛋白GLT-1及EAAC1的阳性表达.致痛1、3 d后，脊髓中GLT-1及EAAC1表达明显升高.致痛后7、10 d表达逐渐降低，接近致痛前的表达水平.结论：足底注射CFA后可致大鼠痛阈显著降低，脊髓中谷氨酸转运蛋白也呈先升高后逐渐降低的变化，谷氨酸转运蛋白可能参与了大鼠炎性疼痛脊髓可塑性变化.     

电针夹背穴在佐剂性关节炎大鼠镇痛过程中磷酸化p38丝裂原活化蛋白激酶电针的变化及作用

目的：观察电针夹脊穴对佐剂性关节炎大鼠背根神经节(dorsal root ganglion，DRG)内磷酸化p38MAPK表达的影响，从信号转导的角度研究电针镇痛的机制。方法：以完全福氏佐剂(CFA)佐剂性关节炎大鼠为疼痛模型，采用免疫组化技术，分别检测空白对照组、模型组、及电针治疗组SD大鼠DGG内磷酸化p38丝裂原活化蛋白激酶(mitogen-activated protein kinase，MAPK)表达特征。结果：与空白对照组[(7．65&;#177;0．72)s]相比，造模后24，48h及7d后，模型组大鼠痛阚下降分别为(6．67&;#177;0．59)，(6．53&;#177;0．73)，(6．64&;#177;0．76)s，同时DRG内p38MAPK磷酸化明显增多(P&;lt;0．05)，尤以48h后增加明显；电针治疗组大鼠在电针夹脊穴治疗后，24，48h及7d后痛阈检测发现其痛阚回升，分别为(7．3&;#177;0．79)，(7．42&;#177;0．93)，和(7．44&;#177;0．89)s，DRG内p38MAPK磷酸化水平下降(P&;lt;0．05)。结论：p38MAPK可能为电针镇痛中一个重要的信号转导分子，其磷酸化在疼痛及电针镇痛过程中其重要作用。     

神阙穴隔药饼灸对应激大鼠胃黏膜损伤的作用

目的:通过观察神阙灸对应激大鼠胃黏膜损伤指数、胃黏膜血流量、胃黏膜组织中降钙素基因相关肽和转化生长因子α含量的影响,探讨神阙灸对应激性溃疡胃粘膜损伤的保护作用及其机制。方法:实验选用健康SD大鼠36只,将其随机分为对照组、模型组、神阙穴隔药饼灸组、非穴隔药饼灸组,每组9只。采用水浸-束缚应激法制备应激性溃疡模型。计算胃黏膜损伤的溃疡指数,用激光多普勒血流仪测定胃黏膜血流量,用放免分析法测定各组大鼠胃黏膜降钙素基因相关肽和转化生长因子α含量的变化。结果:神阙穴隔药饼灸组大鼠胃黏膜损伤指数(19.89±8.43)明显低于模型组(52.22±11.88)(P<0.01)。神阙穴隔药饼灸组大鼠胃黏膜血流量明显高于模型组和非穴隔药饼灸组(P<0.01)。神阙穴隔药饼灸组胃黏膜组织降钙素基因相关肽含量明显高于模型组和非穴隔药饼灸组(P<0.01)。神阙穴隔药饼灸组胃黏膜组织转化生长因子α含量明显高于模型组和非穴隔药饼灸组(P<0.01)。结论:神阙穴隔药饼灸对应激大鼠胃黏膜损伤有保护作用,其机制可能与增加胃黏膜血流量,调节降钙素基因相关肽和转化生长因子α的水平有关。     

从小胶质细胞活化通路探讨化疗诱导大鼠神经病理性疼痛的发生机制

目的:研究脊髓小胶质细胞活化通路在化疗药物诱导的神经病理性疼痛中的作用。方法:大鼠鞘内置管并筛选出痛阈值合格的SD大鼠36只,采用随机配伍的方法分为3组:对照组、模型组、米诺环素组。用隔日腹腔注射长春新碱(125μg/kg)的方法建立化疗药物诱导的神经病理性疼痛动物模型,米诺环素组从建立化疗痛模型前1天起每日鞘内注射工具药米诺环素(100μg/rat,10μL),其他各组同步注射生理盐水。分别用Electronic von Frey测痛仪和热刺痛仪测定大鼠机械痛阈值及热痛阈值,免疫荧光法检测脊髓背角小胶质细胞特异性活化标志物Iba1的表达,Western Blot法检测脊髓CX3CR1蛋白、p-p38MAPK蛋白表达。结果:与对照组相比,模型组大鼠机械痛阈值和热痛阈值显著降低(P<0.05或P<0.01),脊髓背角Iba1蛋白、脊髓CX3CR1蛋白、p-p38MAPK蛋白表达显著升高(P<0.01);与模型组相比,米诺环素组大鼠机械痛阈值和热痛阈值相对升高(P<0.05),脊髓背角Iba1蛋白、脊髓CX3CR1蛋白、p-p38MAPK蛋白表达显著降低(P<0.05或P<0.01)。结论:脊髓小胶质细胞活化通路可能参与了化疗药物诱导的神经病理性疼痛的发生和发展。     

Intrathecal cannabilactone CB(2)R agonist, AM1710, controls pathological pain and restores basal cytokine levels

Spinal glial and proinflammatory cytokine actions are strongly implicated in pathological pain. Spinal administration of the anti-inflammatory cytokine interleukin (IL)-10 abolishes pathological pain and suppresses proinflammatory IL-1β and tumor necrosis factor alpha (TNF-α). Drugs that bind the cannabinoid type-2 receptor (CB(2)R) expressed on spinal glia reduce mechanical hypersensitivity. To better understand the CB(2)R-related anti-inflammatory profile of key anatomical nociceptive regions, we assessed mechanical hypersensitivity and protein profiles following intrathecal application of the cannabilactone CB(2)R agonist, AM1710, in 2 animal models; unilateral sciatic nerve chronic constriction injury (CCI), and spinal application of human immunodeficiency virus-1 glycoprotein 120 (gp120), a model of peri-spinal immune activation. In CCI animals, lumbar dorsal spinal cord and corresponding dorsal root ganglia (DRG) were evaluated by immunohistochemistry for expression of IL-10, IL-1β, phosphorylated p38-mitogen-activated-kinase (p-p38MAPK), a pathway associated with proinflammatory cytokine production, glial cell markers, and degradative endocannabinoid enzymes, including monoacylglycerol lipase (MAGL). AM1710 reversed bilateral mechanical hypersensitivity. CCI revealed decreased IL-10 expression in dorsal spinal cord and DRG, while AM1710 resulted in increased IL-10, comparable to controls. Adjacent DRG and spinal sections revealed increased IL-1β, p-p38MAPK, glial markers, and/or MAGL expression, while AM1710 suppressed all but spinal p-p38MAPK and microglial activation. In spinal gp120 animals, AM1710 prevented bilateral mechanical hypersensitivity. For comparison to immunohistochemistry, IL-1β and TNF-α protein quantification from lumbar spinal and DRG homogenates was determined, and revealed increased DRG IL-1β protein levels from gp120, that was robustly prevented by AM1710 pretreatment. Cannabilactone CB(2)R agonists are emerging as anti-inflammatory agents with pain therapeutic implications.     

'Knock-down' of spinal CB1 receptors produces abnormal pain and elevates spinal dynorphin content in mice

Recent studies demonstrate the possible existence of tonic modulatory control of nociceptive input mediated by spinal cannabinoid receptors (CB1). Accordingly, it is predicted that a reduction in the spinal CB1 receptors may enhance sensitivity to sensory stimuli and a decrease in spinal antinociceptive potency to cannabinoid agonists. An antisense oligodeoxynucleotide (ODN) specific to the CB1 receptor was used to 'knock-down' CB1 receptors in the lumbar spinal cord and dorsal root ganglia by the local, repeated intrathecal (i.th.) administration of the ODN. This treatment resulted in a decrease in lumbar spinal CB1 receptor expression accompanied by a decrease in the response thresholds to both innocuous tactile and noxious thermal stimuli. The antinociceptive action of the CB1 agonist, WIN 55,212-2, by i.th. administration was also significantly attenuated after treatment with the antisense ODN. Similar treatment using a mismatch control ODN had no effect on receptor protein or on sensory thresholds. The effects of the antisense ODN treatment on sensory thresholds were fully reversed after discontinuation of the ODN injection. The antisense ODN treated rats also showed a significant increase in lumbar spinal dynorphin A. Acute i.th. injection of MK-801 or an antidynorphin antiserum blocked the antisense ODN-induced tactile and thermal hypersensitivity. These data support the possibility of endogenous inhibitory cannabinoid tone to limit spinal afferent input of thermal and tactile stimuli. Lifting of this inhibitory tone through a 'knock-down' of spinal CB1 receptors apparently lowers the thresholds for sensory input, as reflected by the actions of MK-801 to block tactile and thermal hypersensitivity. The increased spinal dynorphin may act to further promote afferent outflow and abnormal pain because sequestration of spinal dynorphin with antiserum also reverses the manifestations of abnormal pain following knock-down of CB1 receptors.     

针刺对大鼠局部筋膜和脊髓细胞外信号调节凝酶1/2和P38丝裂原活化蛋白激酶信号通路的影响

目的:观察针刺捻转拉伸大鼠皮下筋膜对局部筋膜和脊髓背角细胞外信号调节激酶1/2（extracellular signal-regulated kinase, ERK1/2）和丝裂原活化蛋白激酶P38(P38 MAPK)信号通路的影响及筋膜结缔组织的形态学变化。方法：20只SD大鼠通过随机分组,每组5只,针刺后三里组和针刺非穴位组进行手针捻转,拉伸刺激组进行拉伸刺激,采用免疫组化技术观察筋膜和脊髓组织中细胞信号蛋白的变化;利用相差显微镜观察拉伸刺激组局部皮下筋膜形态学变化。结果：组织学改变：拉伸刺激组皮下筋膜的纤维以拉伸点为中心呈向心性分布,单位面积内细胞密度增大,细胞骨架和胞核重构成“扁梭形”。 细胞信号蛋白变化：针刺组筋膜结缔组织ERK1/2和P38MAPK表达与对照组相比均有增加,但以非穴组增加显著;ERK1/2与P38MAPK在脊髓中的表达位置由胞质转向胞核,ERK1/2与空白对照组相比差异没有显著性意义;P38MAPK的表达有所增加。结论：针刺对局部浅筋膜的ERK1/2和P38有上调作用,但与脊髓中的信号蛋白增加幅度并不完全一致,说明针刺对机体除了神经调节外,筋膜结缔组织支架可能在微观的信号转导层面对局部细胞分化与增殖具有促进作用。     

Role of CB1 and CB2 cannabinoid receptors in the development of joint pain induced by monosodium iodoacetate

Joint pain is a common clinical problem for which both inflammatory and degenerative joint diseases are major causes. The purpose of this study was to investigate the role of CB1 and CB2 cannabinoid receptors in the behavioral, histological, and neurochemical alterations associated with joint pain. The murine model of monosodium iodoacetate (MIA) was used to induce joint pain in knockout mice for CB1 (CB1KO) and CB2 cannabinoid receptors (CB2KO) and transgenic mice overexpressing CB2 receptors (CB2xP). In addition, we evaluated the changes induced by MIA in gene expression of CB1 and CB2 cannabinoid receptors and μ-, δ- and κ-opioid receptors in the lumbar spinal cord of these mice. Wild-type mice, as well as CB1KO, CB2KO, and CB2xP mice, developed mechanical allodynia in the ipsilateral paw after MIA intra-articular injection. CB1KO and CB2KO demonstrated similar levels of mechanical allodynia of that observed in wild-type mice in the ipsilateral paw, whereas allodynia was significantly attenuated in CB2xP. Interestingly, CB2KO displayed a contralateral mirror image of pain developing mechanical allodynia also in the contralateral paw. All mouse lines developed similar histological changes after MIA intra-articular injection. Nevertheless, MIA intra-articular injection produced specific changes in the expression of cannabinoid and opioid receptor genes in lumbar spinal cord sections that were further modulated by the genetic alteration of the cannabinoid receptor system. These results revealed that CB2 receptor plays a predominant role in the control of joint pain manifestations and is involved in the adaptive changes induced in the opioid system under this pain state.     

Interleukin‐6 induces microglial CX3CR1 expression in the spinal cord after peripheral nerve injury through the activation of p38 MAPK

Peripheral nerve injury leading to neuropathic pain induces the upregulation of interleukin (IL)‐6 and microglial CX3CR1 expression, and activation of p38 mitogen‐activated protein kinase (MAPK) in the spinal cord. Here, we investigated whether IL‐6 regulates CX3CR1 expression through p38 MAPK activation in the spinal cord in rats with chronic constriction injury (CCI) of the sciatic nerve. Similar temporal changes in the expression of IL‐6, phosphorylated p38 MAPK and CX3CR1 were observed following CCI. The increases in CX3CR1 expression, p38 MAPK activation and pain behavior after CCI were suppressed by blocking IL‐6 action with a neutralizing antibody, while they were enhanced by supplying exogenous recombinant rat IL‐6 (rrIL‐6). rrIL‐6 also induced increases in spinal CX3CR1 expression, p38 MAPK activation and pain behavior in naïve rats without nerve injury. Furthermore, treatment with the p38 MAPK‐specific inhibitor, SB203580, suppressed the increase in CX3CR1 expression induced by CCI or rrIL‐6 treatment. Finally, blocking CX3CR1 or p38 MAPK activation prevented the development of mechanical allodynia and thermal hyperalgesia induced by CCI or rrIL‐6 treatment. These results suggest a new mechanism of neuropathic pain, in which IL‐6 induces microglial CX3CR1 expression in the spinal cord through p38 MAPK activation, enhancing the responsiveness of microglia to fractalkine in the spinal cord, thus playing an important role in neuropathic pain after peripheral nerve injury.     

双柏散敷药联合特定电池波谱照射治疗腰椎间盘突出症疗效观察及护理

目的探讨双柏散敷药联合特定电池波谱(TDP)照射治疗腰椎间盘突出症疗效,并总结护理要点。方法将125例腰椎间盘突出症患者随机分为观察组65例与对照组60例,对照组患者采用推拿、电针理疗法,观察组患者在对照组的基础上加双柏散敷药联合TDP照射。观察两组患者两个疗程后疼痛及治疗情况。结果两组患者治疗后疼痛VAS评分及治疗效果比较,均P0.05,差异具有统计学意义,观察组患者疼痛评分明显低于对照组,治疗效果明显优于对照组。结论在推拿、针灸等理疗基础上,加双柏散敷药联合TDP照射可提高椎间盘突出症治疗效果和缓解腰患者疼痛程度。护理方面应做好敷药及TDP照射护理工作。     

鞘内氯胺酮或(和)吗啡注射对切口痛大鼠脊髓NOS活性和NO含量的影响

【目的】在大鼠切口痛模型中研究鞘内注射(it)氯胺酮或(和)吗啡对脊髓一氧化氮合酶(NOS)活性和一氧化氮(NO)含量的影响。【方法】雄性SD大鼠64只,随机分为8组, 每组8只, 分别为假手术组, 对照组, 术后氯胺酮治疗组, 术前氯胺酮治疗组, 术后吗啡治疗组, 术前吗啡治疗组, 术后氯胺酮加吗啡治疗组和术前氯胺酮加吗啡治疗组。按Brennan法制成大鼠切口痛模型, 以vonFrey细丝法(机械性痛觉过敏)、热辐射法(热痛觉过敏)和累积疼痛评分法观察疼痛的行为学变化,以分光光度法测定脊髓NOS活性和NO含量。【结果】与假手术组比较,在术后2h时对照组大鼠的vonFrey纤毛刺激缩爪阈值明显降低(P<0. 01),热刺激缩爪潜伏期明显缩短(P<0. 01),累积疼痛评分明显升高(P<0. 01 );与对照组比较,术后/术前吗啡治疗组和术后/术前吗啡加氯胺酮治疗组大鼠的vonFrey纤毛刺激缩爪阈值均明显增加(P<0. 01),热刺激缩爪潜伏期均明显延长(P<0. 01),累积疼痛评分均明显降低(P<0. 01);与假手术组比较, 对照组大鼠脊髓NOS活性和NO含量明显增加(P<0. 01);与对照组比较,术前氯胺酮治疗组、术前吗啡治疗组和术前氯胺酮加吗啡治疗组能使脊髓的NOS活性明显降低, NO含量明显减少(P<0. 01或P<0. 05)。【结论】在大鼠切口痛模型中,术前it吗啡和氯胺酮加     

隔药饼灸对兔动脉粥样硬化斑块中基质金属蛋白酶-2,9 mRNA表达的影响

目的观察隔药饼灸对兔动脉粥样硬化(AS)中基质金属蛋白酶-2,9(MMP-2,9)表达的影响,探讨隔药饼灸对兔动脉粥样硬化斑块稳定性的影响。方法将75只新西兰大耳白兔,通过高脂饲料喂养及免疫损伤法建立兔AS模型。然后随机分为5组,每组15只,即：空白组(空白对照组);模型组(AS模型组);直接灸组(AS模型+艾炷直接灸);隔药饼灸组(AS模型+隔药饼灸);西药组(AS模型＋阿托伐他汀)。运用原位杂交法检测兔动脉粥样硬化斑块中MMP-2,9 mRNA的表达。结果隔药饼灸、直接灸和西药均能抑制兔动脉粥样硬化斑块中MMP-2和MMP-9 mRNA的表达(P<0.01或P<0.05);隔药饼灸组和西药组MMP-2和MMP-9 mRNA的表达低于直接灸组(P<0.01或P<0.05)。结论隔药饼灸、直接灸和西药通过抑制兔动脉粥样硬化斑块中MMPs的表达,起到稳定动脉粥样硬化斑块的作用,且隔药饼灸和西药抑制MMPs表达的作用优于直接灸。     

Pronociceptive effects of spinal dynorphin promote cannabinoid-induced pain and antinociceptive tolerance

Recent studies indicate that sustained opioid administration produces increased expression of spinal dynorphin, which promotes enhanced sensitivity to non-noxious and noxious stimuli. Such increased "pain" may manifest behaviorally as a decrease in spinal antinociceptive potency. Here, the possibility of similar mechanisms in the antinociception of spinal cannabinoids was explored. Response thresholds to non-noxious mechanical and noxious thermal stimuli were assessed. Antinociception was determined using the 52 degrees C tail-flick test. Mice received repeated WIN 55,212-2, its inactive enantiomer, WIN 55,212-3 or vehicle (i.th., bid, 5 days). WIN 55,212-2, but not WIN 55,212-3 or vehicle, produced a time-related increased sensitivity to non-noxious and noxious stimuli. WIN 55,212-2, but not WIN 55,212-3 or vehicle, elicited a significant increase in lumbar spinal dynorphin content at treatment day 5. Increased sensitivity to mechanical and thermal stimuli produced by WIN 55,212-2 was reversed to baseline levels by i.th. MK-801 or dynorphin antiserum; control serum had no effect. WIN 55,212-2, but not WIN 55,212-3 or vehicle, produced dose-related antinociception and repeated administration resulted in antinociceptive tolerance. While MK-801 and dynorphin antiserum did not alter acute antinociception produced by WIN 55,212-2, these substances significantly blocked antinociceptive tolerance when given immediately prior to WIN 55,212-2 challenge on day 5. Daily MK-801 pretreatments, prior to WIN 55,212-2 injection, also produced a significant block of antinociceptive tolerance. These data suggest that like opioids, repeated spinal administration of a cannabinoid CB1 agonist elicits abnormal pain, which results in increased expression of spinal dynorphin. Manipulations that block cannabinoid-induced pain also block the behavioral manifestation of cannabinoid tolerance.     

大麻素受体1和2在肝纤维化模型C57小鼠肝组织中的表达

目的 观察大麻素受体1( CB1)和受体2(CB2)在肝纤维化模型C57小鼠肝组织表达及意义.方法 30只C57小鼠被随机分为3组,即正常对照组、模型对照组和模型秋水仙碱组,每组10只.采用四氯化碳( CCl4)腹腔注射制造小鼠肝纤维化模型,通过免疫组织化学染色方法检测肝组织中CB1和CB2的表达,同时进行肝组织炎症(G)评分和纤维化(S)评分.结果 模型对照组、模型秋水仙碱组及正常对照组肝组织G评分及S评分比较,差异有统计学意义(F=125.41,P=0.00;F=99.18,P=0.00),且模型对照组肝组织G评分及S评分均显著高于模型秋水仙碱组,差异均有统计学意义(P均＜0.01).模型对照组、模型秋水仙碱组肝组织及正常对照组CB1和CB2评分比较,差异有统计学意义(F=29.27,P=0.00;F=36.99,P=0.00),且模型对照组肝组织CB1和CB2评分均显著高于模型秋水仙碱组,差异具有统计学意义(P＜0.05或P＜0.01).模型对照组和模型秋水仙碱组中CB1、CB2、G和S评分四者之间均具有相关性(P均＜0.05),且随着G、S评分的不断增加,CB1和CB2评分逐渐增加.结论 CB1和CB2在肝纤维化模型C57小鼠肝组织中表达均明显增强,与肝组织炎症和肝纤维化程度有显著相关性.