The influence of chronic stress on multiple opioid peptide systems in the rat: pronounced effects upon dynorphin in spinal cord

Recurrent exposure to intermittent electrical foot-shock (30 min, twice daily) for 7 days caused an increase in immunoreactive (ir) dynorphin and ir-alpha-neo-endorphin in lumbar and cervical (but not thoracic) spinal cord as measured 16 h following the final session. At this time the level of ir-Met-enkephalin-Arg6-Gly7-Leu8 (MEAGL) was also increased at the lumbar level. An acute foot-shock depleted spinal cord dynorphin in chronically stressed but not in naive rats. No alterations in levels of ir-dynorphin or ir-MEAGL were seen in discrete brain tissues. In contrast to the brain, where no effects were seen, the levels of beta-endorphin increased in both lobes of the pituitary. This change, however, was not accompanied by an alteration in levels of beta-endorphin in plasma. These data show that chronic foot-shock stress selectively influences particular pools of opioid peptides, predominantly those derived from proenkephalin B in the spinal cord and from proopiomelanocortin in the anterior pituitary. It is suggested that alterations observed in the spinal cord reflect enhanced activity of the proenkephalin B system in response to chronic nociceptive stimulation.     

腺苷A1受体与к阿片肽受体激活对异丙肾上腺素诱导的心肌细胞肥大的交互作用

目的观察腺苷A1受体与κ阿片肽受体(κ-OR)激活对异丙肾上腺素(Iso)诱导的心肌细胞肥大的交互作用及机制。方法体外培养大鼠乳鼠心肌细胞,以Iso 10μmol/L诱导心肌细胞肥大,观察腺苷A1受体激动剂R(-)-N6-(2-phenylIsopropyl)adenosine(R-PIA)1μmol/L和κ-OR激动剂U50,488H1μmol/L对其作用,进一步探讨腺苷A1受体拮抗剂8-cyclopentyl-1,3-dipropylxanthine(CPDPX)0.1μmol/L存在时κ-OR的激活对细胞肥大的影响和κ-OR拮抗剂nor-binaltorphimine(NOR-BNI)1μmol/L存在时腺苷A1受体的激活对心肌细胞肥大的影响。通过Lowry法测心肌细胞蛋白含量;消化分离法及计算机图像分析系统测细胞体积;以Fluo-3/AM为荧光探针,共聚焦显微镜下测量心肌细胞内[Ca2+]i变化;RT-PCR法检测心肌细胞心房钠尿肽(ANP)的mRNA表达。结果 10μmol/LIso可以诱导心肌细胞肥大,1μmol/L的R-PIA(腺苷A1受体激动剂)可以明显抑制Iso诱导的心肌细胞蛋白合成增加、体积增大、ANPmRNA表达增加、心肌细胞内[Ca2+]i荧光强度增大,该抑制作用可以被1μmol/Lκ-OR拮抗剂NOR-BNI部分阻断;κ-OR激动剂U50,488H1μmol/L可以明显抑制Iso诱导的心肌细胞蛋白合成增加、体积增大、ANPmRNA表达增加、心肌细胞内[Ca2+]i荧光强度增大,该抑制作用可以被腺苷A1受体拮抗剂CPDPX部分阻断。结论腺苷可通过激动A1受体、阿片肽可通过激动κ受体抑制Iso诱导的心肌肥大,二者可以通过影响心肌细胞内[Ca2+]i浓度的增大而交互抑制Iso诱导的心肌肥大。     

Morphine‐6‐glucuronide (M6G) for postoperative pain relief

Morphine‐6‐glucuronide (M6G) is morphine's active metabolite acting at the μ‐opioid receptor. Recent experimental human studies and 5 of 6 randomized clinical trials indicate that M6G causes adequate and long lasting pain relief comparable to morphine. There are various observations that M6G is associated with a reduction in the severity of side effects normally associated with opioid use, such as reduced postoperative nausea and vomiting (PONV) and reduced respiratory depression. The present drug profile provides a review of the pharmacological properties of M6G, the clinical evidence relating to its efficacy and safety, and discusses its future role in the treatment of postoperative pain.     

依托咪酯所致肌阵挛机制与药物防治

背景 依托咪酯麻醉诱导引起肌阵挛日益引起关注,其相关机制尚不清楚. 目的 就依托咪酯诱导肌阵挛的预防策略进行综述,为临床上对该副作用预防策略的选用提供参考. 内容 综述依托咪酯诱导肌阵挛的发生机制、易发因素、预防药物及方法,综合对比各种方法的利弊. 趋向 依托咪酯是一种经典的静脉麻醉药,尤其适合老年人或存在心血管疾病血流动力学不稳定的患者,只有了解其诱导肌阵挛的发生机制和预防策略,才能有效避免或减少肌阵挛的发生,为临床提供更加安全有效的用药指南.     

CX3C趋化因子受体1对骨癌痛大鼠吗啡耐受时脊髓背角μ受体和辣椒素受体表达的影响

目的 评价CX3C趋化因子受体1(CX3 CR1)对骨癌痛大鼠吗啡耐受时脊髓背角μ受体和辣椒素受体(TRPVl)表达的影响.方法 清洁级成年雌性SD大鼠,体重180-200 g,月龄3月,经L3.4棘突间隙行鞘内置管,取鞘内置管成功的大鼠48只,采用随机数字表法,将大鼠随机分为4组(n=12):对照组(A组)、鞘内注射生理盐水组(AM组)、鞘内注射IgG组(GM组)和鞘内注射CX3CR1中和抗体组(BM组).A组仪手术暴露右侧胫骨七段;其余3组右侧胫骨上段骨髓腔注入Walker256 乳腺癌细胞10μl(400个/ μl)建立骨癌痛模型,术后第10天开始鞘内注射吗啡20tg/kg,2次/d,连续7d,建立骨癌痛-吗啡耐受模型,注射吗啡第8天分别经鞘内注射相应溶液10μl,1次/d,连续3d.分别于接种Walker 256乳腺癌细胞前(T0)、接种后第3、6、9天、注射吗啡第3、7天、鞘内注射抗体第3天(T1-T6)时测定机械缩足阈值(MWT)和机械缩足持续时间(MWD),于T6时测定痛阈后处死大鼠,取脊髓L4-6节段组织,采用Western blot法检测脊髓背角小胶质细胞CX3 CR1蛋白的表达,采用免疫组化法检测神经元μ受体和TRPV1的表达.结果 与A组比较,BM组T2.3.5时、AM组和GM组T2,3,5,6时MWT下降,MWD升高,T6时CX3CR1蛋白和TRPV1表达上调,μ受体表达下调(P＜0.01);与AM组和GM组比较,BM组T6时MWT上升,MWD降低,CX3CR1蛋白和TRPV1表达下调,μ受体表达上调(P＜0.01).AM组和GM组上述指标差异无统计学意义(p＞0.05).结论 CX3CR1可通过下调大鼠脊髓背角μ受体和上调TRPVI参与骨癌痛大鼠吗啡耐受的形成.     

瘦素/阿片促黑素细胞皮质素原/神经肽Y信号在胃转流术治疗2型糖尿病中的作用

目的 探讨瘦素(Leptin)、神经肽Y(NPY)、阿片促黑素细胞皮质素原(POMC)信号通路在胃转流手术治疗2型糖尿病中的作用及机制.方法采用20只成年SD雄性大鼠成功建立2型糖尿病大鼠模型,随机分为糖尿病非手术对照组(NO组,n=10)和糖尿病手术组[Roux-en-Y胃旁路术(RYGB)组,n=10],另外再选10只正常大鼠作为正常对照组(NC组),对手术组实施胃转流手术,分别于术前、术后检测各组大鼠血糖(GLU)、总胆固醇(TCH)及甘油三酯(TG)、Leptin水平,每天定时监测大鼠饮水量、饮食量以及体质量的变化,术后第4周取大鼠下丘脑,检测下丘脑中NPY、POMC mRNA的表达水平.结果术后第4周,RYGB组大鼠血糖、血脂以及进食、水量已接近正常水平,Leptin和NPY mRNA水平分别由术前的(4.58±0.37)μg/L、1.89 ±0.24降低到(3.10±0.38) μg/L、0.95±0.19(P＜0.01),而POMC mRNA水平则由术前的0.78±0.26升高至1.70±0.31(P＜0.01).结论 胃转流手术可以改善2型糖尿病的血糖水平,Leptin可能通过NPY、POMC神经元信号调节2型糖尿病的能量代谢平衡,提示Leptin与下丘脑NPY、POMC调节通路可能在胃转流手术后2型糖尿病病情缓解过程中发挥重要作用.     

外周炎症时大鼠背根神经节细胞μ-和κ-阿片受体mRNA的表达

目的观察外周炎症时大鼠背根神经节(dorsalrootganglion,DRG)细胞μ-和κ-阿片受体mRNA表达的变化。方法用角叉菜胶(carrageenan,CAR)在大鼠右后足皮下注射产生外周炎症,分别于正常和炎症后6、12、24和72h取右L4~5DRG。用原位杂交的方法观察正常及炎症期间DRG细胞μ-和κ-阿片受体mRNA表达的变化。结果正常大鼠的部分DRG细胞内可见μ-和κ-阿片受体mRNA表达。外周炎症后6h,表达μ-和κ-阿片受体mRNA的DRG细胞的数和μ-和κ-阿片受体mRNA表达量增加,24h表达量最高,72h下降至正常。结论外周炎症能使大鼠DRG细胞μ-和κ-阿片受体mRNA表达增加。提示外周炎症时大鼠DRG细胞μ-和κ-阿片受体合成增加。为阿片类物质应用于外周镇痛提供理论依据。     

吗啡对外周刺激诱导的大鼠海马CA1区长时程增强(LTP)的抑制作用

目的观察吗啡急性中枢应用,对外周电刺激坐骨神经诱导的海马CA1区LTP及海马痛觉调制作用的影响,并探讨其可能的机制。方法25只雄性SD大鼠200～260g,随机分为5组。单刺激坐骨神经,各组侧脑室给药后给予强直刺激,观察场电位的变化。结果单刺激坐骨神经可在海马CA1区诱导出场电位(21.43±4.54)μV,其潜伏期较长(169.94±14.65)ms及阈值较高(平均15V),据此,推断是C类纤维诱发的;强直刺激后海马CA1区可出现持续时间在2h以上LTP现象;中、大剂量吗啡侧脑室注射可抑制海马CA1区LTP,纳洛酮可阻断这种作用。结论LTP是海马痛觉调制的生物学机制之一,阿片受体在其中起重要作用。吗啡对C-类纤维诱导的海马CA1区LTP的抑制作用可能通过阿片受体实现。     

Dynorphin-(1–13)-Like Immunoreactivity in Central Nervous System and Pituitary Gland of Spontaneously Hypertensive Rats

We determined by radioimmunoassay concentrations of dynorphin-(1–13)-like immunoreactivity in the central nervous system and pituitary gland of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). Compared to WKYs, SHRs had significantly lower levels of dynorphin-(1–13)-like immunoreactivity in the hypothalamus and pituitary gland. However, such immunoreactivity in the cerebral cortex, caudate nucleus, diencephalon, brainstem and spinal cord of SHRs and WKYs were similar.