目的:探讨针刺疗法联合电刺激治疗对老年脑卒中后抑郁患者的临床疗效。方法: 78例脑卒中后抑郁患者被随机分为常规治疗组(常规治疗的同时给予健康宣教)和联合治疗组(在常规治疗组基础上采用针刺治疗,同时联合低频电刺激治疗),治疗4周后...目的:探讨针刺疗法联合电刺激治疗对老年脑卒中后抑郁患者的临床疗效。方法: 78例脑卒中后抑郁患者被随机分为常规治疗组(常规治疗的同时给予健康宣教)和联合治疗组(在常规治疗组基础上采用针刺治疗,同时联合低频电刺激治疗),治疗4周后比较两组患者的汉密顿抑郁量表(HAMD)评分和疗效。结果:与治疗前比较,治疗后两组患者HAMD评分显著降低,且与常规治疗组比较,联合治疗组降低更显著[(19.72±2.04)分比(14.94±1.86)分], P 均=0.001;联合治疗组临床总有效率显著高于常规治疗组(87.18%比64.1%, P =0.018)。结论:针刺疗法结合低频电刺激治疗脑卒中后抑郁疗效显著,值得临床运用。展开更多
OBJECTIVE Thienorphine,a new oripavine derivative,has shown to possess stronger antinociceptive effects and better oral bioavailability compared to buprenorphine.The present study examines the effect of thienorphine o...OBJECTIVE Thienorphine,a new oripavine derivative,has shown to possess stronger antinociceptive effects and better oral bioavailability compared to buprenorphine.The present study examines the effect of thienorphine on c AMP-dependent protein kinase A(PKA) activity in CHO cells expressing μ-,κ-,δ-and ORL1 receptors.In addition,we further examined its analgesic effect in vivo.METHODS The effect of thienorphine on cA MP-dependent PKA redistribution and cA MP inhibition were analyzed in CHO-PKAcatEGFP cells.PKA redistribution assays in CHO-PKAcatEGFP cells stably expressing μ-,κ-,δ-and ORL1 receptors were analyzed by high-throughput screening system to elucidate the efficacy of agonists or antagonists on opioid receptors.Moroever,the antinociceptive effects of thienorphine in vivo were examined using hot plate test.RESULTS Briefly,the maximum inhibition of thienorphine on PKA activity was about 36%,100%,100%and 12% in CHO-μ/κ/δ/ORL1-PKAcatE GFP cel s,respectively.In addition,thienorphine concentrationdependently inhibited the PKA activity with EC50 value of(22.7±18.1) nmol·L^(-1) in CHO-κ-PKAcatE GFP cels and(12.4±7.7) nmol·L^(-1) in CHO-δ-PKAcatE GFP cells.Thienorphine induced approximately 50%antinociceptive effect in mice lacking μ receptors compared to their wild-type controls(P<0.05).Also,the κ and δ selective antagonist nor-binaltorphimine,naltrindole decreased approximately 50%-60% in % MPE of theinorphine in μ-KO mice,respectively.The ORL1 receptor selective antagonist J113397 had no effect in %MPE of theinorphine in μ-KO mice.CONCLUSION Thienorphine induces analgesia through bindingκ-and δ-,or by partially binding μ-opioid receptor,thus further regulating the cAMP-PKA activity.Therefore,thienorphine may be used in acute or chronic pain with minimal addictive potential.展开更多
OBJECTIVE Chronic morphine exposure reduced analgesic efficiency leads to morphine tolerance which was mediated byβ-arrestin signaling of MOR,but the further mecha⁃nism remains unclear.METHODS AND RESULTS Morphine to...OBJECTIVE Chronic morphine exposure reduced analgesic efficiency leads to morphine tolerance which was mediated byβ-arrestin signaling of MOR,but the further mecha⁃nism remains unclear.METHODS AND RESULTS Morphine tolerance and dependence was attenuated by overexpression of ABIN-1 in mice brain.ABIN-1 in hippocampus or vascular nucleus participated in morphine tolerance and physical dependence.ABIN-1 through AHD2 re⁃gion interacted with MOR to regulate its function.As the result,the peptide of AHD2 could also de⁃lay morphine tolerance as ABIN-1.Two lines of evidence may explain the function of ABIN-1 on morphine tolerance.First,ABIN-1 inhibited the phosphorylation and internalization of MOR after acute or chronic agonists treatment through inter⁃action with MOR.Second,The formation of ABIN-1-β-arrestin-2 complexes promoted the translocation ofβ-arrestin-2 to plasma mem⁃brane and accelerated the ubiquitination ofβ-ar⁃restin-2 to degrade it.However,the function kjj⁃mice brain.CONCLUSION ABIN-1 may targetβ-arrestin-2 to regulate MOR function and provides a potential strategy for enhancing morphine anal⁃gesia without increasing analgesic tolerance.展开更多
Aim:To determine the proteins that interact with the carboxyl-terminal of theμopioid receptor(MOR-C)after chronic morphine exposure.Methods:The brain cDNA library of chronic morphine treatment rats was screened using...Aim:To determine the proteins that interact with the carboxyl-terminal of theμopioid receptor(MOR-C)after chronic morphine exposure.Methods:The brain cDNA library of chronic morphine treatment rats was screened using rat MOR-C to investigate the regulator of opioids dependence in the present study.The brain cDNA library from chronic morphine-dependent rats was constructed using the SMART(Switching Mechanism At 5′end of RNA Transcript)technique.Bacterial two-hybrid system was used to screening the rat MOR-C interacting proteins from the cDNA library.RT-qPCR and immunoblotting were used to determine the variation of MOR-C interacting proteins in rat brain after chronic morphine treatment.Column overlay assays,immunocytochemistry and coimmunoprecipitation were used to demonstrate the interaction of MOR-C and p75NTR-associated cell death executor(NADE)or A20-binding inhibitor of nuclear factor kB(ABIN-1).Results:21 positive proteins,including 19 known proteins were screened to interact with rat MOR-C.Expression of several of these proteins was altered in specific rat brain regions after chronic morphine treatment.Among these proteins,ABIN-1 and NADE were confirmed to interact with rat MOR-C by in vitro proteinprotein binding and coimmunoprecipitation in Chinese hamster ovary(CHO)cells and rat brain with or without chronic morphine treatment.Saturation binding studies showed that ABIN-1 had no effect on MOR binding.However,the interaction of ABIN-1 and MOR inhibited the activation of G proteins induced by DAMGO([D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin).MOR phosphorylation,ubiquitination,and internalization induced by DAMGO were decreased in Chinese hamster ovary cells that coexpressed MOR and ABIN-1.The suppression of forskolinstimulated adenylylcyclase by DAMGO was also inhibited by the interaction of ABIN-1with MOR.In addition,extracellular signal-regulated kinase activation was also negatively regulated by overexpression of ABIN-1.These data suggest that ABIN-1 is a negative coregulator of MOR activation,phosphorylation,and internalization in vitro.ABIN-1 also inhibited morphine-induced hyperlocomotion in zebrafish larvae(AB strain).By utilization of an antisense morpholino oligonucleotide(MO)gene knockdown technology,the ABIN-1MO-injected zebrafish larvae showed a significant increase(approximately 60%)in distance moved compared with control MO-injected larvae after acute morphine treatment(P≤0.01).Conclusion:Understanding the rat MOR-C interacting proteins and the proteins variation under chronic morphine treatment may be critical for determining the pathophysiological basis of opioid tolerance and addiction.Among these proteins,ABIN-1 negatively regulates MOR function in vitro and in vivo.Other MOR-C interacting proteins’influence on the opioid tolerance and addiction need further study.展开更多
Thenorphine is a new parrtail agonist of opioid recepter synthesized by our institute of pharmacology and toxicology.There are double effects of agonist and antegonist on opioid recepter. The agonist effect was showed...Thenorphine is a new parrtail agonist of opioid recepter synthesized by our institute of pharmacology and toxicology.There are double effects of agonist and antegonist on opioid recepter. The agonist effect was showed by analgesia. The analgesic properties are stronger efficacy (ED50 1 mg/kg po) ; longer duration (t1/2 9h) and lower dependence (no展开更多
文摘目的:探讨针刺疗法联合电刺激治疗对老年脑卒中后抑郁患者的临床疗效。方法: 78例脑卒中后抑郁患者被随机分为常规治疗组(常规治疗的同时给予健康宣教)和联合治疗组(在常规治疗组基础上采用针刺治疗,同时联合低频电刺激治疗),治疗4周后比较两组患者的汉密顿抑郁量表(HAMD)评分和疗效。结果:与治疗前比较,治疗后两组患者HAMD评分显著降低,且与常规治疗组比较,联合治疗组降低更显著[(19.72±2.04)分比(14.94±1.86)分], P 均=0.001;联合治疗组临床总有效率显著高于常规治疗组(87.18%比64.1%, P =0.018)。结论:针刺疗法结合低频电刺激治疗脑卒中后抑郁疗效显著,值得临床运用。
基金National Natural Science Foundation of China(8147319481773709).
文摘OBJECTIVE Thienorphine,a new oripavine derivative,has shown to possess stronger antinociceptive effects and better oral bioavailability compared to buprenorphine.The present study examines the effect of thienorphine on c AMP-dependent protein kinase A(PKA) activity in CHO cells expressing μ-,κ-,δ-and ORL1 receptors.In addition,we further examined its analgesic effect in vivo.METHODS The effect of thienorphine on cA MP-dependent PKA redistribution and cA MP inhibition were analyzed in CHO-PKAcatEGFP cells.PKA redistribution assays in CHO-PKAcatEGFP cells stably expressing μ-,κ-,δ-and ORL1 receptors were analyzed by high-throughput screening system to elucidate the efficacy of agonists or antagonists on opioid receptors.Moroever,the antinociceptive effects of thienorphine in vivo were examined using hot plate test.RESULTS Briefly,the maximum inhibition of thienorphine on PKA activity was about 36%,100%,100%and 12% in CHO-μ/κ/δ/ORL1-PKAcatE GFP cel s,respectively.In addition,thienorphine concentrationdependently inhibited the PKA activity with EC50 value of(22.7±18.1) nmol·L^(-1) in CHO-κ-PKAcatE GFP cels and(12.4±7.7) nmol·L^(-1) in CHO-δ-PKAcatE GFP cells.Thienorphine induced approximately 50%antinociceptive effect in mice lacking μ receptors compared to their wild-type controls(P<0.05).Also,the κ and δ selective antagonist nor-binaltorphimine,naltrindole decreased approximately 50%-60% in % MPE of theinorphine in μ-KO mice,respectively.The ORL1 receptor selective antagonist J113397 had no effect in %MPE of theinorphine in μ-KO mice.CONCLUSION Thienorphine induces analgesia through bindingκ-and δ-,or by partially binding μ-opioid receptor,thus further regulating the cAMP-PKA activity.Therefore,thienorphine may be used in acute or chronic pain with minimal addictive potential.
文摘OBJECTIVE Chronic morphine exposure reduced analgesic efficiency leads to morphine tolerance which was mediated byβ-arrestin signaling of MOR,but the further mecha⁃nism remains unclear.METHODS AND RESULTS Morphine tolerance and dependence was attenuated by overexpression of ABIN-1 in mice brain.ABIN-1 in hippocampus or vascular nucleus participated in morphine tolerance and physical dependence.ABIN-1 through AHD2 re⁃gion interacted with MOR to regulate its function.As the result,the peptide of AHD2 could also de⁃lay morphine tolerance as ABIN-1.Two lines of evidence may explain the function of ABIN-1 on morphine tolerance.First,ABIN-1 inhibited the phosphorylation and internalization of MOR after acute or chronic agonists treatment through inter⁃action with MOR.Second,The formation of ABIN-1-β-arrestin-2 complexes promoted the translocation ofβ-arrestin-2 to plasma mem⁃brane and accelerated the ubiquitination ofβ-ar⁃restin-2 to degrade it.However,the function kjj⁃mice brain.CONCLUSION ABIN-1 may targetβ-arrestin-2 to regulate MOR function and provides a potential strategy for enhancing morphine anal⁃gesia without increasing analgesic tolerance.
基金This work was supported by the National Natural Science Foundation of China(30901799,81473194),the Natural Science Foundation of Beijing(7092078).
文摘Aim:To determine the proteins that interact with the carboxyl-terminal of theμopioid receptor(MOR-C)after chronic morphine exposure.Methods:The brain cDNA library of chronic morphine treatment rats was screened using rat MOR-C to investigate the regulator of opioids dependence in the present study.The brain cDNA library from chronic morphine-dependent rats was constructed using the SMART(Switching Mechanism At 5′end of RNA Transcript)technique.Bacterial two-hybrid system was used to screening the rat MOR-C interacting proteins from the cDNA library.RT-qPCR and immunoblotting were used to determine the variation of MOR-C interacting proteins in rat brain after chronic morphine treatment.Column overlay assays,immunocytochemistry and coimmunoprecipitation were used to demonstrate the interaction of MOR-C and p75NTR-associated cell death executor(NADE)or A20-binding inhibitor of nuclear factor kB(ABIN-1).Results:21 positive proteins,including 19 known proteins were screened to interact with rat MOR-C.Expression of several of these proteins was altered in specific rat brain regions after chronic morphine treatment.Among these proteins,ABIN-1 and NADE were confirmed to interact with rat MOR-C by in vitro proteinprotein binding and coimmunoprecipitation in Chinese hamster ovary(CHO)cells and rat brain with or without chronic morphine treatment.Saturation binding studies showed that ABIN-1 had no effect on MOR binding.However,the interaction of ABIN-1 and MOR inhibited the activation of G proteins induced by DAMGO([D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin).MOR phosphorylation,ubiquitination,and internalization induced by DAMGO were decreased in Chinese hamster ovary cells that coexpressed MOR and ABIN-1.The suppression of forskolinstimulated adenylylcyclase by DAMGO was also inhibited by the interaction of ABIN-1with MOR.In addition,extracellular signal-regulated kinase activation was also negatively regulated by overexpression of ABIN-1.These data suggest that ABIN-1 is a negative coregulator of MOR activation,phosphorylation,and internalization in vitro.ABIN-1 also inhibited morphine-induced hyperlocomotion in zebrafish larvae(AB strain).By utilization of an antisense morpholino oligonucleotide(MO)gene knockdown technology,the ABIN-1MO-injected zebrafish larvae showed a significant increase(approximately 60%)in distance moved compared with control MO-injected larvae after acute morphine treatment(P≤0.01).Conclusion:Understanding the rat MOR-C interacting proteins and the proteins variation under chronic morphine treatment may be critical for determining the pathophysiological basis of opioid tolerance and addiction.Among these proteins,ABIN-1 negatively regulates MOR function in vitro and in vivo.Other MOR-C interacting proteins’influence on the opioid tolerance and addiction need further study.
文摘Thenorphine is a new parrtail agonist of opioid recepter synthesized by our institute of pharmacology and toxicology.There are double effects of agonist and antegonist on opioid recepter. The agonist effect was showed by analgesia. The analgesic properties are stronger efficacy (ED50 1 mg/kg po) ; longer duration (t1/2 9h) and lower dependence (no
