AIM:To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices.METHODS:Experimental rats were fed a modified Lieber-De Carli alcohol(6%) and high-fat(65%...AIM:To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices.METHODS:Experimental rats were fed a modified Lieber-De Carli alcohol(6%) and high-fat(65%) diet(AHF) for 10 wk while control animals received a regular rodent chow diet.Weekly behavioral tests determinedmechanical and heat sensitivity.In week 10 a fasting glucose tolerance test was performed,measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal(i.p.) injection of glucose.Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin.Pancreas sections were also stained with Sirius red and fast green to quantify collagen content.Insulinexpressing cells were identified immunohistochemically in separate sections.Tissue staining density was quantified using Image J software.After mechanical and heat sensitivity became stable(weeks 6-10) in the AHF-fed animals,three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity:a Group Ⅱ metabotropic glutamate receptor specific agonist(2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate(APDC,3 mg/kg,ip; Tocris,Bristol,United Kingdom),nociceptin(20,60,200 nmol/kg,ip; Tocris),and morphine sulfate(3 mg/kg,μ-opioid receptor agonist; Baxter Healthcare,Deerfield,IL,United States).RESULTS:Histological analysis of pancreas and liver determined that unlike control rats,AHF fed animals had pancreatic fibrosis,acinar and beta cell atrophy,with steatosis in both organs.Fat vacuolization was significantly increased in AHF fed rats(6.4% ± 1.1% in controls vs 23.8% ± 4.2%,P < 0.05).Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls(127.4 ± 9.2 mg/d L in controls vs 161.0 ± 8.6 mg/d L,P < 0.05).This concurred with a 3.5 fold higher incidence of single and small 2-10 cell insulin-positive cell clusters(P < 0.05).Insulin express展开更多
Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperre...Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure （MABP） in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats （250～300 g body weight, 2. 5～3 months old） were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ （0. 5 mg/kg） induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI（60 μg/kg）, 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.展开更多
Orphanin FQ (OFQ) is a new modulatory peptide which was found in 1994. It mediates in morphine analgesia and electroacupuncture analgesia. The interaction between OFQ and 5-hydroxytryptamine (5-HT) on analgesia was ob...Orphanin FQ (OFQ) is a new modulatory peptide which was found in 1994. It mediates in morphine analgesia and electroacupuncture analgesia. The interaction between OFQ and 5-hydroxytryptamine (5-HT) on analgesia was observed using the method of intracerebroventricular microinjection. The results showed that cumulative i. c.v. administration of gradually increasing doses of 5-HT produced a dose-dependent analgesia, and administration of different doses of OFQ separateness had no significant effect on tail flick latency, but 1 or 10 μg OFQ could reverse the analgesia induced by 5-HT, suggesting that OFQ could antagonize the analgesia induced by 5-HT in rat brain.展开更多
Objective This study aimed to investigate the possible role of Orphanin FQ(OFQ) in the regulation of hypothalamic gonadotropin-releasing hormone(GnRH) secretion. Methods The method of push-pull perfusion and radioimmu...Objective This study aimed to investigate the possible role of Orphanin FQ(OFQ) in the regulation of hypothalamic gonadotropin-releasing hormone(GnRH) secretion. Methods The method of push-pull perfusion and radioimmunoassay(RIA) were adopted to examine the secretory profile of GnRH in the median eminence(ME) in freely moving ovariectomized(OVX) rats after intracerebroventricular(icv) injection of OFQ and/or [Nphe1]NC(1-13)NH2(NC13),a competitive antagonists of the opioid receptor-like 1 receptor(ORL1 recep...展开更多
基金Supported by National Institutes of Health,No.NINDS R01 NS39041
文摘AIM:To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices.METHODS:Experimental rats were fed a modified Lieber-De Carli alcohol(6%) and high-fat(65%) diet(AHF) for 10 wk while control animals received a regular rodent chow diet.Weekly behavioral tests determinedmechanical and heat sensitivity.In week 10 a fasting glucose tolerance test was performed,measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal(i.p.) injection of glucose.Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin.Pancreas sections were also stained with Sirius red and fast green to quantify collagen content.Insulinexpressing cells were identified immunohistochemically in separate sections.Tissue staining density was quantified using Image J software.After mechanical and heat sensitivity became stable(weeks 6-10) in the AHF-fed animals,three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity:a Group Ⅱ metabotropic glutamate receptor specific agonist(2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate(APDC,3 mg/kg,ip; Tocris,Bristol,United Kingdom),nociceptin(20,60,200 nmol/kg,ip; Tocris),and morphine sulfate(3 mg/kg,μ-opioid receptor agonist; Baxter Healthcare,Deerfield,IL,United States).RESULTS:Histological analysis of pancreas and liver determined that unlike control rats,AHF fed animals had pancreatic fibrosis,acinar and beta cell atrophy,with steatosis in both organs.Fat vacuolization was significantly increased in AHF fed rats(6.4% ± 1.1% in controls vs 23.8% ± 4.2%,P < 0.05).Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls(127.4 ± 9.2 mg/d L in controls vs 161.0 ± 8.6 mg/d L,P < 0.05).This concurred with a 3.5 fold higher incidence of single and small 2-10 cell insulin-positive cell clusters(P < 0.05).Insulin express
文摘Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure （MABP） in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats （250～300 g body weight, 2. 5～3 months old） were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ （0. 5 mg/kg） induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI（60 μg/kg）, 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.
文摘Orphanin FQ (OFQ) is a new modulatory peptide which was found in 1994. It mediates in morphine analgesia and electroacupuncture analgesia. The interaction between OFQ and 5-hydroxytryptamine (5-HT) on analgesia was observed using the method of intracerebroventricular microinjection. The results showed that cumulative i. c.v. administration of gradually increasing doses of 5-HT produced a dose-dependent analgesia, and administration of different doses of OFQ separateness had no significant effect on tail flick latency, but 1 or 10 μg OFQ could reverse the analgesia induced by 5-HT, suggesting that OFQ could antagonize the analgesia induced by 5-HT in rat brain.
基金supported by the National Natural Science Foundation of China (No. 39870914)the Key Project on Traditional Chinese Medicine of Shanghai Medical Health Bureau (No. 20003).
文摘Objective This study aimed to investigate the possible role of Orphanin FQ(OFQ) in the regulation of hypothalamic gonadotropin-releasing hormone(GnRH) secretion. Methods The method of push-pull perfusion and radioimmunoassay(RIA) were adopted to examine the secretory profile of GnRH in the median eminence(ME) in freely moving ovariectomized(OVX) rats after intracerebroventricular(icv) injection of OFQ and/or [Nphe1]NC(1-13)NH2(NC13),a competitive antagonists of the opioid receptor-like 1 receptor(ORL1 recep...
