The Study On The Expression Of OFQ/N In Antropyloro In The Rats With Diabetic Gastroparesis

Background:Kassender recognized a sympiomatic gastric retention in diabetic in 1958 and coined the term gastroparesis diabeticorum. Since the original report, the term has been used to reflect symptomatic as well as a sympiomatic gastric retention and more recently, the term diabetic dyspepsia has been used to reflect the spectrum of postprandial symptoms in diabetics attributable to upper gastrointestinal dysfunctions, including those associated with delayed gastric emptying[3], Thus, whereas nausea, vomiting, and early satiation after meals were the classical symptoms of gastroparesis, the term dyspepsia in addition reflects bloating, fullness, and pain in the upper abdomen[4]. Because lacking of understanding of the aetiology, current medical treatments for DGP are often ineffective.It has been shown that predominant symptoms in DGP correlate with the enteric nervous system (ENS) abnormalities, gut hormone responses and intestinal myopathy in several clinical experiments. Animal experiments has show that stimulant laxatives can damage ENS and cause the change of some enteric neurotransmitters and thus the slosly gastrointestinal tract transit occurs.The peptide nociceptin, also called orphanin-FQ(N/OFQ), is a 17-amino-acide peptide ade was identified in 1995. Because it binds an opiod receptor like 1(ORL1) receptor with high affinity, it has been reported to be an endogeneous agonist for 0RL1 receptor. In situ hybridization studies has revealed the wide distribution of the ORL1 receptor mRNA in the central nervous system of rats, especially in the coli involved in pain control, so most of researches focused on the role of N/OFQ in analgesic. However, by the activation of the ORL1 receptor, N/OFQ can also influences reward, anxiety, feeding and memory processes, cardiovascular and renal function, gastric and intestinal molity and secretions. Despite its homologous to classical opioids:dynorphin A, OFQ/ORL1 system represents anew peptide-based signaling pathway, which is pharmacologically distinct from opioid system.Gastrointestinal motility is controlled by alocal network of intramural nerves. Gastrointestinal tract is an important model system for the research of pharmacological characterization of opioid. So if N/OFQ can also acts as a brain-bowel peptide like classical opioid, it may has a role in the regulation of gastrointestinal functions. Probe to the distribution and function of N/OFQ and ORL1 receptor in gastrointestinal tract will contribute to the overall understanding of the characteristics of this neuronic system, accelerating related researches of the gastrointestinal motility regulated by OFQ/ORL1 receptor system and promote the general comprehensive of opioid system.Methods:To explore etiopathogenesis of DGP, the model of rats was established by administration of asingle intrperitoneal injection of STZ(30mg/Kg body weight).we explored the distribution of OFQ in gastrointestinal tract and the changes of OFQ in tissue of antropyloro of rats by immunohistochemical S-P method. The rate of gastrointestinal transit was also measured.Result:1. The gastrointestinal transit of DGP rats was decreased significantly.2.OFQ was highly expressed in the myenteric plexus of rats gastrointestinal tract but not in the muscle cells. Orphanin FQ immunoreactive(OFQ-IR) neurons and nerve fibers were visualized in the myenteric plexus of stomach. Like the classical opioid peptides, OFQ located in the ENS and may be involved in gastrointestinal motility,endocrine,mucosa flood and immunity function. The immunoreactivity of OFQ in the myenteric plexus in antropyloro of the rats with DGP was Significantly decreased as compared with the normal control group and trauma control group. The data indicated the OFQ located in the ENS of rats and the abnormalities of it may be involved in the dysmotility of DGP.Conclusions:These findings indicate that OFQ is a brain-gut peptide and have a role in the control of gastrointestinal functions. The abnormalities of enteric nervous system are responsible for DGP. It also indicate that chronic hyperglycemia can induce disorganization of dynamic and injure ENS and accelerate the pathological changes of DGP. But the pathophysiology of DGP is complex and not easily approached through datas from animals alone. Further studies according to the clinical characteristics of DGP patients could provide additional insight into this issue.