Ischemic stroke is a global epidemic condition due to an inadequate supply of blood and oxygen to a specific area of brain either by arterial blockage or by narrowing of blood vessels.Despite having advancement in the...Ischemic stroke is a global epidemic condition due to an inadequate supply of blood and oxygen to a specific area of brain either by arterial blockage or by narrowing of blood vessels.Despite having advancement in the use of thrombolytic and clot removal medicine,significant numbers of stroke patients are still left out without option for treatment.In this review,we summarize recent research work on the activation ofδ-opioid receptor as a strategy for treating ischemic stroke-caused neuronal injury.Moreover,as activation ofδ-opioid receptor by a non-peptidicδ-opioid receptor agonist also modulates the expression,maturation and processing of amyloid precursor protein andβ-secretase activity,the potential role of these effects on ischemic stroke caused dementia or Alzheimer’s disease are also discussed.展开更多
Objective To clarify the role of propofol in controlling incisional pain and its potential effects on the spinal opioid receptor expression. Methods A postoperative model of nociception was established in male Sprague...Objective To clarify the role of propofol in controlling incisional pain and its potential effects on the spinal opioid receptor expression. Methods A postoperative model of nociception was established in male Sprague-Dawley rats weighing 200 -250 g. A total of 96 rats were randomly divided into 8 groups. All drugs were administered intravenously either 5 rain pre-operation or 5 rain post-operation. The analgesic effects of systemic propofol were demonstrated by the measurement of a cumulative pain score （ CPS ）. After that, the lumbar enlargement of the spinal cord was removed to evaluate the mRNA level of the μ-opioid receptor （ MOR ） and δ-opioid receptor （ DOR） by RT-PCR. Results CPS and DOR mRNA expressions significantly increased after the operation. Both propofol post-treatment and propofol pre-treatment groups showed significant suppression of the increased CPS and the expression of DOR mRNA evoked by pain stimulation. Interestingly, propofol pre-treatment had a more pronounced effect in decreasing CPS and the expression of DOR mRNA. Furthermore, these observations were dose-dependent. MOR mRNA expression significantly increased after operation in all animals and propofol treatment had no impact on it. Conclusion Based on these findings, we suggest that propofol can serve as a valuable adjunct in acute postoperative pain management. Systemic propofol induces an analgesic effect on acute incisional pain in a dose-dependant manner, and this effect is mediated in the spinal cord and may be associated with the spinal DOR.展开更多
Objective： To study the precise role of DOR in the regulation of sodium channels at present. Methods： With Xenopus oocytes co-expressing sodium channel subtype 2 （Nav1.2） and DOR. Results： 1） Nav1.2 expression i...Objective： To study the precise role of DOR in the regulation of sodium channels at present. Methods： With Xenopus oocytes co-expressing sodium channel subtype 2 （Nav1.2） and DOR. Results： 1） Nav1.2 expression induced tetrodotoxin-sensitive inward currents; 2） DOR expression reduced the inward currents; 3） activation of DOR reduced the amplitude of the current and rightly shifted the activation curve of the current in the oocytes with both Nav1.2 and DOR, but not in ones with Nav1.2 alone; 4） the DOR agonist-induced inhibition of Nay 1.2 currents was in a dose-dependent manner and saturable; 5） the DOR agonist had no effect on naive oocytes. Conclusion： These data represent the first demonstration that activation of DOR inhibits Na^＋ channel function by decreasing the amplitude of sodium currents and increasing its threshold of activation. This novel finding has far-reaching impacts on novel solutions of certain neurological disorders such as hypoxic/ischemic injury, epilepsy and pain. Also, our data may improve the understanding of the mechanisms underlying acupuncture since acupuncture is known to activate the brain opioid system.展开更多
目的探讨δ阿片受体激动剂DADLE对脓毒症大鼠肾功能的保护作用及其机制。方法Sprague-Dawley（SD）大鼠72只，随机（随机数字法）分为假手术组（sham-operatedgroup，SHAM组）、脓毒症组（sepsisgroup，SEP组）和DADLE处理组（DADLE-tre...目的探讨δ阿片受体激动剂DADLE对脓毒症大鼠肾功能的保护作用及其机制。方法Sprague-Dawley（SD）大鼠72只，随机（随机数字法）分为假手术组（sham-operatedgroup，SHAM组）、脓毒症组（sepsisgroup，SEP组）和DADLE处理组（DADLE-treatedgroup，DADLE组），每组2，4只。SHAM组打开腹腔后关闭，SEP组采用盲肠结扎穿孔（cecalhgation and puncture，CLP）法建立脓毒症模型，DADIE组在CLP后即静脉注射5mg/kgDALDE。各组在建模后2h，6h和10h各取8只，检测以下指标：①血清尿素氮（BUN）、肌酐（Cr）和陉．微球蛋白（-MG）。②血清肿瘤坏死因子α（TNF-α）和白介素6（IL-6）。③左肾组织三磷酸腺苷（ATP）含量。④右肾病理观察。多组间比较用方差分析，组间两两比较采用q检验。结果①DADLE组BUN和Cr分别在6h和10h比SEP组显著降低（P〈0．01），DADLE组β2-MG在各时间点均显著低于SEP组（P〈0．01）。②与SHAM组比较，SEP组和DADLE组在各时间点TNF-α和IL-6均显著升高，DADLE组显著低于SEP组（P〈0．01）。③与SHAM组比较，SEP组和DAD皿组肾组织的ATP在各时间点均降低（P〈0．01），DADLE组高于SEP组，三组间差异具有统计学意义（P〈0．01）。④光镜下见SEP组逐步出现肾小管上皮细胞肿胀、空泡变性、脱落和坏死，基底膜消失，DADLE组的肾小管上皮细胞脱落和坏死程度轻于SEP组，基底膜保持完整。结论DADLE可以改善脓毒症大鼠。肾功能，降低炎症因子水平，减缓肾组织ATP的下降，减轻肾小管上皮细胞的损害，具有肾保护作用。展开更多
基金supported by the National Institute of Neurological Disorders and Stroke under research grant NS088084(to HW)
文摘Ischemic stroke is a global epidemic condition due to an inadequate supply of blood and oxygen to a specific area of brain either by arterial blockage or by narrowing of blood vessels.Despite having advancement in the use of thrombolytic and clot removal medicine,significant numbers of stroke patients are still left out without option for treatment.In this review,we summarize recent research work on the activation ofδ-opioid receptor as a strategy for treating ischemic stroke-caused neuronal injury.Moreover,as activation ofδ-opioid receptor by a non-peptidicδ-opioid receptor agonist also modulates the expression,maturation and processing of amyloid precursor protein andβ-secretase activity,the potential role of these effects on ischemic stroke caused dementia or Alzheimer’s disease are also discussed.
基金Supported by the National Natural Science Foundation of China (No.30672020)
文摘Objective To clarify the role of propofol in controlling incisional pain and its potential effects on the spinal opioid receptor expression. Methods A postoperative model of nociception was established in male Sprague-Dawley rats weighing 200 -250 g. A total of 96 rats were randomly divided into 8 groups. All drugs were administered intravenously either 5 rain pre-operation or 5 rain post-operation. The analgesic effects of systemic propofol were demonstrated by the measurement of a cumulative pain score （ CPS ）. After that, the lumbar enlargement of the spinal cord was removed to evaluate the mRNA level of the μ-opioid receptor （ MOR ） and δ-opioid receptor （ DOR） by RT-PCR. Results CPS and DOR mRNA expressions significantly increased after the operation. Both propofol post-treatment and propofol pre-treatment groups showed significant suppression of the increased CPS and the expression of DOR mRNA evoked by pain stimulation. Interestingly, propofol pre-treatment had a more pronounced effect in decreasing CPS and the expression of DOR mRNA. Furthermore, these observations were dose-dependent. MOR mRNA expression significantly increased after operation in all animals and propofol treatment had no impact on it. Conclusion Based on these findings, we suggest that propofol can serve as a valuable adjunct in acute postoperative pain management. Systemic propofol induces an analgesic effect on acute incisional pain in a dose-dependant manner, and this effect is mediated in the spinal cord and may be associated with the spinal DOR.
基金the Science Foundation of Shanghai Municipal Commission of Science and Technology(05DZ19745,06DZ19732,064319053,07DZ19722,07DZ19733)the National Basic Research Program of China(973 Program,2005CB523306)+1 种基金Shanghai Leading Academic Discipline Project(B112 and T0302)NIH-HD3485
文摘Objective： To study the precise role of DOR in the regulation of sodium channels at present. Methods： With Xenopus oocytes co-expressing sodium channel subtype 2 （Nav1.2） and DOR. Results： 1） Nav1.2 expression induced tetrodotoxin-sensitive inward currents; 2） DOR expression reduced the inward currents; 3） activation of DOR reduced the amplitude of the current and rightly shifted the activation curve of the current in the oocytes with both Nav1.2 and DOR, but not in ones with Nav1.2 alone; 4） the DOR agonist-induced inhibition of Nay 1.2 currents was in a dose-dependent manner and saturable; 5） the DOR agonist had no effect on naive oocytes. Conclusion： These data represent the first demonstration that activation of DOR inhibits Na^＋ channel function by decreasing the amplitude of sodium currents and increasing its threshold of activation. This novel finding has far-reaching impacts on novel solutions of certain neurological disorders such as hypoxic/ischemic injury, epilepsy and pain. Also, our data may improve the understanding of the mechanisms underlying acupuncture since acupuncture is known to activate the brain opioid system.
基金the National Basic Research Development Program of China (No. 2005CB523306)National Natural Science Foundation of China (No. 30670721)+1 种基金Science and Technology Commission of Shanghai Municipality (No. 06DZ19734, 04DZ19836, 05DZ19745)The 6th Postgraduate Student Foundation of Fudan University and NIH (No. HD-34852)
文摘目的探讨δ阿片受体激动剂DADLE对脓毒症大鼠肾功能的保护作用及其机制。方法Sprague-Dawley（SD）大鼠72只，随机（随机数字法）分为假手术组（sham-operatedgroup，SHAM组）、脓毒症组（sepsisgroup，SEP组）和DADLE处理组（DADLE-treatedgroup，DADLE组），每组2，4只。SHAM组打开腹腔后关闭，SEP组采用盲肠结扎穿孔（cecalhgation and puncture，CLP）法建立脓毒症模型，DADIE组在CLP后即静脉注射5mg/kgDALDE。各组在建模后2h，6h和10h各取8只，检测以下指标：①血清尿素氮（BUN）、肌酐（Cr）和陉．微球蛋白（-MG）。②血清肿瘤坏死因子α（TNF-α）和白介素6（IL-6）。③左肾组织三磷酸腺苷（ATP）含量。④右肾病理观察。多组间比较用方差分析，组间两两比较采用q检验。结果①DADLE组BUN和Cr分别在6h和10h比SEP组显著降低（P〈0．01），DADLE组β2-MG在各时间点均显著低于SEP组（P〈0．01）。②与SHAM组比较，SEP组和DADLE组在各时间点TNF-α和IL-6均显著升高，DADLE组显著低于SEP组（P〈0．01）。③与SHAM组比较，SEP组和DAD皿组肾组织的ATP在各时间点均降低（P〈0．01），DADLE组高于SEP组，三组间差异具有统计学意义（P〈0．01）。④光镜下见SEP组逐步出现肾小管上皮细胞肿胀、空泡变性、脱落和坏死，基底膜消失，DADLE组的肾小管上皮细胞脱落和坏死程度轻于SEP组，基底膜保持完整。结论DADLE可以改善脓毒症大鼠。肾功能，降低炎症因子水平，减缓肾组织ATP的下降，减轻肾小管上皮细胞的损害，具有肾保护作用。
基金supported by the grants of NIH-HD34852,NIH-AT004422,AHA-0755993T,STCSM-05DZ19745973 Program-2006CB504509n part by the Intramural Research Program of the NIH and NIEHS
