Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu （ST25） and Shangjuxu （ST37） once daily over a period of 7 days. Results show that suspended moxibustion significa...Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu （ST25） and Shangjuxu （ST37） once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.展开更多
There is a growing body of evidence showing that periaqueductal gray (PAG) and nucleus accumbens (N. accumbens) play important roles in the modulation of nociception. In our previous study of the mechanisms of morphin...There is a growing body of evidence showing that periaqueductal gray (PAG) and nucleus accumbens (N. accumbens) play important roles in the modulation of nociception. In our previous study of the mechanisms of morphine analgesia we found that opioid antagonist naloxone injected into either of the two nuclei, PAG or N. accumbens, could展开更多
Opioid growth factor(OGF),chemically termed[Met5]-enkephalin,and its receptor,OGF receptor(OGFr),form a biological axis that tonically regulates cell proliferation by delaying the G1/S interface of the cell cycle unde...Opioid growth factor(OGF),chemically termed[Met5]-enkephalin,and its receptor,OGF receptor(OGFr),form a biological axis that tonically regulates cell proliferation by delaying the G1/S interface of the cell cycle under homeostatic conditions or in neoplasia.Modulation of the OGF-OGFr pathway mediates the course of pancreatic cancer,with exogenous OGF or upregulation of OGFr repressing growth of human pancreatic cancer cells in culture and in nude mice.OGF therapy alone or in combination with standard chemotherapies such as gemcitabine and 5-fluorouracil results in enhanced inhibition of DNA synthesis and tumor growth.Molecular manipulation of OGFr confirms that the receptor is specific for OGF’s inhibitory action.Preclinical studies have warranted PhaseⅠand PhaseⅡclinical trials using OGF infusions as a treatment for patients with advanced,unresectable pancreatic cancers.OGF,an endogenous neuropeptide,is a safe,non-toxic,and effective biotherapy that utilizes the OGF-OGFr axis to mediate pancreatic tumor progression.展开更多
After 20min electric field stimulation,L-enkephalin （L-ENK） content in the rabbitear artery declined from the control value of 38.99±17.29 to 12.55±1.96pg/mg of wet tissue（n=12）,and M-enkephalin （M-ENK...After 20min electric field stimulation,L-enkephalin （L-ENK） content in the rabbitear artery declined from the control value of 38.99±17.29 to 12.55±1.96pg/mg of wet tissue（n=12）,and M-enkephalin （M-ENK） content from 134.67±8.11 to 73.68±17.96pg/mg of wet tis-sue （n=6）,both being significantly decreased.This effect was not influenced after blockade ofadrenergic receptor by yohimbine.Contractions of artery strips induced by electric field stimulationwere enhanced distinctly after pretreatment of the artery strips with naloxone,an opioid receptorblocker,and with pronase,but not after pretreatment with trypsin.The results suggested that the re-lease of endogenous enkephalins in the ear artery could be induced by electric field stimulation andx<sub>2</sub>-receptor might not participate in the release course,The release amount of ENK from the ar-terv strips increased when the stimulus freduency increased within the range of 2 Hz to 8 Hz.展开更多
OBJECTIVE To investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS 3×10~6CT26 cells were implanted subcutaneously in BALB/c mice....OBJECTIVE To investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS 3×10~6CT26 cells were implanted subcutaneously in BALB/c mice.Four days after,MENK was peritoneally administrated at the concentration of 20 mg·kg^(-1) for 14 d.The percentage of MDSCs in bone marrow,spleen,blood,tumor and liver were detected by flow cytometry.Non-esterified fatty acid(NEFA),triglycerides(TG)and total cholesterol(T-CHO)in liver homogenate were tested by a NEFA test kit,a TG test kit and a T-CHO test kit respectively.qRT-PCR and Western blot were used to measure m RNA and protein levels of inflammation-,glycometabolsim-and lipometabolsim-associated indexes in liver.RESULTS MENK decreased percentages of MDSCs in bone marrow,spleen,blood and tumor in colon cancer mice.MENK-treated mice displayed elevated ratio of CD4^+T and CD8^+T cells in spleen as well as increased T and B lymphocytes proliferation.Meanwhile,MENK also ameliorated liver damage reflected by lower levels of GPT and GOT in serum and reduced risks of cancer-associated index including inflammation,high lipid and high glucose.Furthermore,MENK lowered down the levels of NEFA,TG and T-CHO in liver homogenate.MENK treatment decreased expression of p-STAT3,increased expression of p-AKT,IRS1 and Glut4 at protein level as well as reduced lipogenesis-associated genes and elevated glycolysis-associated genes in liver of tumor bearing mice.Also,abated expression of genes associated with MDSCs generation(M-CSF,GM-CSF,IL-6,IL^(-1)β)and migration(S100A9,KC)was observed within shrunken subcutaneous tumor by MENK intervention.CONCLUSION MENK has the ability to strength immune function against colon cancer by reducing MDSCs and improving liver metabolism.展开更多
Objective To observe the effects of methionine enkephalin (M Enk) on migration of macrophages from mice with impaired liver and its immunomodulatory mechanisms. Methods Liver of mice was impaired by feeding CCl 4 and ...Objective To observe the effects of methionine enkephalin (M Enk) on migration of macrophages from mice with impaired liver and its immunomodulatory mechanisms. Methods Liver of mice was impaired by feeding CCl 4 and macrophage migration inhibitory factor (MMIF) was produced by Con A stimulated spleen lymphocytes. Inhibition of macrophage migration was measured in reaction system by adding M Enk. Results Migration of macrophages in both liver impaired and control group were suppressed by MMIF, but the suppression might be reversed by adding 1 μmol/L M Enk ( P <0.05).M Enk could significantly inhibit in vitro both of the combination of MMIF with macrophages and production of MMIF from lymphocytes ( P <0.01).Macrophages from liver imparied group showed a higher sensitivity compared to the control group ( P <0.05).Conclusion The study suggests that opioid peptieds play an important role in the modulation of the immune response under stress as liver impairment.展开更多
Drug addiction is a chronic brain disorder characterized by withdrawal symptoms that occur during drug abstinence and a high tendency of relapse.Compared with the currently available pharmacological interventions,acup...Drug addiction is a chronic brain disorder characterized by withdrawal symptoms that occur during drug abstinence and a high tendency of relapse.Compared with the currently available pharmacological interventions,acupuncture therapy has the potential to help drug addicts stay away from drugs without major adverse side effects.It has taken decades of research to optimize the parameters of electrical acupoint stimulation for detoxification and for relapse prevention,as well as to establish a safe and easy procedure by which drug addicts can use it on themselves.The discovery that acupuncture can trigger the release of opioid substances from the brain in the 1970s provided the inspiration.Following this,basic research on animals made it possible to understand the mechanisms of action and establish the procedure for treating drug addictions.This article reviews the past,present,and foreseeable future regarding the use of acupuncture-related technique for the treatment of opiate addiction from the perspective of translational medicine.展开更多
Background Preconditioning with repeated electroacupuncture （EA） could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu（μ）-, d...Background Preconditioning with repeated electroacupuncture （EA） could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu（μ）-, delta（δ）- or kappa（κ）-opioid receptors are involved in the neuroprotecUon induced by repeated EA preconditioning. Methods The rats were pretreated with naltrindole （NTI）, nor-binaltorphimine （nor-BNI） or D-Phe-Cys-Tyr-D- Trp-Om-Thr-Pen-Thr-NH2 （CTOP）, which is a highly selective δ-, κ- or μ-opioid receptor antagonist respectively, before each EA preconditioning （30 minutes per day, 5 days）. Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion （MCAO） was induced for 120 minutes. The brain infarct volume was determined with 2,3,5-tdphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats. Results The EA preconditioning reduced brain infarct volume compared with the control rats （P=-0.000）. Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats （P〈0.001）. But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats （P=-0.000）. The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats （P=-0.000）. Conclusion Repeated EA preconditioning stimulates the release of enkephalins, which may bind 5- and p-opioid receptors to induce the tolerance against focal cerebral ischemia.展开更多
The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin.Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the ...The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin.Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the presentation and changes of mechanical allodynia and thermal hyperalgesia of operated mouse hind paws.The results suggested that endogenous enkephalin may not be involved in the antihyperalgesic effect of gabapentin.展开更多
It is established that opioid peptides are involved in the regulation of various physiological processes including the higher function of the brain. We have reported that peripheral administration of enkephalin impair...It is established that opioid peptides are involved in the regulation of various physiological processes including the higher function of the brain. We have reported that peripheral administration of enkephalin impaired memory retention in mice. This effect was reversed by naloxone. We further found that bestatin, an aminopeptidase inhibitor, when injected peripherally or into amygdala introduced memory impairment which mimiced the effect of enkephalin. The present study examined the influence of hippocampal and peripheral enkephalin on operant defence conditioning in rats, with an attempt to detect the action of central enkephalin on memory.展开更多
基金supported by the National Basic Research Program of China (973 Program) (No. 2009CB522900)the National Natural Science Foundation of China (No. 30973783)the Shanghai Leading Academic Discipline Project (No. S30304)
文摘Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu （ST25） and Shangjuxu （ST37） once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.
文摘There is a growing body of evidence showing that periaqueductal gray (PAG) and nucleus accumbens (N. accumbens) play important roles in the modulation of nociception. In our previous study of the mechanisms of morphine analgesia we found that opioid antagonist naloxone injected into either of the two nuclei, PAG or N. accumbens, could
基金Supported by grants from NIH in part,Philip Morris United States,and The Pennsylvania Department of Heath,as well as generous gifts from the Paul I and Anna E Shockey Family Foundation
文摘Opioid growth factor(OGF),chemically termed[Met5]-enkephalin,and its receptor,OGF receptor(OGFr),form a biological axis that tonically regulates cell proliferation by delaying the G1/S interface of the cell cycle under homeostatic conditions or in neoplasia.Modulation of the OGF-OGFr pathway mediates the course of pancreatic cancer,with exogenous OGF or upregulation of OGFr repressing growth of human pancreatic cancer cells in culture and in nude mice.OGF therapy alone or in combination with standard chemotherapies such as gemcitabine and 5-fluorouracil results in enhanced inhibition of DNA synthesis and tumor growth.Molecular manipulation of OGFr confirms that the receptor is specific for OGF’s inhibitory action.Preclinical studies have warranted PhaseⅠand PhaseⅡclinical trials using OGF infusions as a treatment for patients with advanced,unresectable pancreatic cancers.OGF,an endogenous neuropeptide,is a safe,non-toxic,and effective biotherapy that utilizes the OGF-OGFr axis to mediate pancreatic tumor progression.
文摘After 20min electric field stimulation,L-enkephalin （L-ENK） content in the rabbitear artery declined from the control value of 38.99±17.29 to 12.55±1.96pg/mg of wet tissue（n=12）,and M-enkephalin （M-ENK） content from 134.67±8.11 to 73.68±17.96pg/mg of wet tis-sue （n=6）,both being significantly decreased.This effect was not influenced after blockade ofadrenergic receptor by yohimbine.Contractions of artery strips induced by electric field stimulationwere enhanced distinctly after pretreatment of the artery strips with naloxone,an opioid receptorblocker,and with pronase,but not after pretreatment with trypsin.The results suggested that the re-lease of endogenous enkephalins in the ear artery could be induced by electric field stimulation andx<sub>2</sub>-receptor might not participate in the release course,The release amount of ENK from the ar-terv strips increased when the stimulus freduency increased within the range of 2 Hz to 8 Hz.
基金supported by National Natural Science Foundation of China(81673440 and 81473585)
文摘OBJECTIVE To investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS 3×10~6CT26 cells were implanted subcutaneously in BALB/c mice.Four days after,MENK was peritoneally administrated at the concentration of 20 mg·kg^(-1) for 14 d.The percentage of MDSCs in bone marrow,spleen,blood,tumor and liver were detected by flow cytometry.Non-esterified fatty acid(NEFA),triglycerides(TG)and total cholesterol(T-CHO)in liver homogenate were tested by a NEFA test kit,a TG test kit and a T-CHO test kit respectively.qRT-PCR and Western blot were used to measure m RNA and protein levels of inflammation-,glycometabolsim-and lipometabolsim-associated indexes in liver.RESULTS MENK decreased percentages of MDSCs in bone marrow,spleen,blood and tumor in colon cancer mice.MENK-treated mice displayed elevated ratio of CD4^+T and CD8^+T cells in spleen as well as increased T and B lymphocytes proliferation.Meanwhile,MENK also ameliorated liver damage reflected by lower levels of GPT and GOT in serum and reduced risks of cancer-associated index including inflammation,high lipid and high glucose.Furthermore,MENK lowered down the levels of NEFA,TG and T-CHO in liver homogenate.MENK treatment decreased expression of p-STAT3,increased expression of p-AKT,IRS1 and Glut4 at protein level as well as reduced lipogenesis-associated genes and elevated glycolysis-associated genes in liver of tumor bearing mice.Also,abated expression of genes associated with MDSCs generation(M-CSF,GM-CSF,IL-6,IL^(-1)β)and migration(S100A9,KC)was observed within shrunken subcutaneous tumor by MENK intervention.CONCLUSION MENK has the ability to strength immune function against colon cancer by reducing MDSCs and improving liver metabolism.
文摘Objective To observe the effects of methionine enkephalin (M Enk) on migration of macrophages from mice with impaired liver and its immunomodulatory mechanisms. Methods Liver of mice was impaired by feeding CCl 4 and macrophage migration inhibitory factor (MMIF) was produced by Con A stimulated spleen lymphocytes. Inhibition of macrophage migration was measured in reaction system by adding M Enk. Results Migration of macrophages in both liver impaired and control group were suppressed by MMIF, but the suppression might be reversed by adding 1 μmol/L M Enk ( P <0.05).M Enk could significantly inhibit in vitro both of the combination of MMIF with macrophages and production of MMIF from lymphocytes ( P <0.01).Macrophages from liver imparied group showed a higher sensitivity compared to the control group ( P <0.05).Conclusion The study suggests that opioid peptieds play an important role in the modulation of the immune response under stress as liver impairment.
基金supported by the National Basic Research Program of China(Nos.2007CB512501,2009CB522003).
文摘Drug addiction is a chronic brain disorder characterized by withdrawal symptoms that occur during drug abstinence and a high tendency of relapse.Compared with the currently available pharmacological interventions,acupuncture therapy has the potential to help drug addicts stay away from drugs without major adverse side effects.It has taken decades of research to optimize the parameters of electrical acupoint stimulation for detoxification and for relapse prevention,as well as to establish a safe and easy procedure by which drug addicts can use it on themselves.The discovery that acupuncture can trigger the release of opioid substances from the brain in the 1970s provided the inspiration.Following this,basic research on animals made it possible to understand the mechanisms of action and establish the procedure for treating drug addictions.This article reviews the past,present,and foreseeable future regarding the use of acupuncture-related technique for the treatment of opiate addiction from the perspective of translational medicine.
基金the National Natural Science Foundation of China(No.30471664).
文摘Background Preconditioning with repeated electroacupuncture （EA） could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu（μ）-, delta（δ）- or kappa（κ）-opioid receptors are involved in the neuroprotecUon induced by repeated EA preconditioning. Methods The rats were pretreated with naltrindole （NTI）, nor-binaltorphimine （nor-BNI） or D-Phe-Cys-Tyr-D- Trp-Om-Thr-Pen-Thr-NH2 （CTOP）, which is a highly selective δ-, κ- or μ-opioid receptor antagonist respectively, before each EA preconditioning （30 minutes per day, 5 days）. Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion （MCAO） was induced for 120 minutes. The brain infarct volume was determined with 2,3,5-tdphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats. Results The EA preconditioning reduced brain infarct volume compared with the control rats （P=-0.000）. Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats （P〈0.001）. But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats （P=-0.000）. The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats （P=-0.000）. Conclusion Repeated EA preconditioning stimulates the release of enkephalins, which may bind 5- and p-opioid receptors to induce the tolerance against focal cerebral ischemia.
文摘The aim of this study was to investigate the role of endogenous enkephalin in the cerebral antihyperalgesic action of gabapentin.Neuropathic pain models and antihyperalgesic effect of gabapentin were confirmed by the presentation and changes of mechanical allodynia and thermal hyperalgesia of operated mouse hind paws.The results suggested that endogenous enkephalin may not be involved in the antihyperalgesic effect of gabapentin.
基金Project supported by the National Natural Science Foundation of China.
文摘It is established that opioid peptides are involved in the regulation of various physiological processes including the higher function of the brain. We have reported that peripheral administration of enkephalin impaired memory retention in mice. This effect was reversed by naloxone. We further found that bestatin, an aminopeptidase inhibitor, when injected peripherally or into amygdala introduced memory impairment which mimiced the effect of enkephalin. The present study examined the influence of hippocampal and peripheral enkephalin on operant defence conditioning in rats, with an attempt to detect the action of central enkephalin on memory.
