| Background:The sphincter of Oddi is located in the duodenum descending segment (paragraph) under the inside part of the intestinal wall within the lumen side containing prominent vertical lines, oblique lines, and circular smooth muscle. Consists of three parts:a simple part of the surrounding bile ducts called biliary sphincter, pancreatic duct sphincter partially, after the merger of common bile duct sphincter of the Department for the nipple. The sphincter of Oddi regular contraction and relaxation is to ensure that the gallbladder filling and discharge, an important condition for the maintenance of bile duct pressure. The sphincter of Oddi dysfunction or disorder is the biliary system and other diseases, one of the important dynamic incentives. Currently recognized, the sphincter of Oddi dysfunction is essentially spasticity. Wei has been confirmed by the United States and high cholesterol abnormal changes can occur SO motivation; high cholesterol can cause sphincter of Oddi dysfunction in rabbits, resulting in impaired systolic and diastolic function in rabbit SO. Among them, high cholesterol effects on the biliary system dynamics have been reported in the literature.At home and abroad about the roles of the movement mechanism of gastrointestinal research literature more, but on the sphincter of Oddi mechanism study also relatively small. China has studied the Chinese peony active ingredients proven through a variety of ways paeoniflorin gastrointestinal smooth muscle relaxation, while paeoniflorin whether the same relaxing effect the sphincter of Oddi and the same signal transduction mechanism, currently no relevant reports. Based on the above understanding, the present study, production of rabbit sphincter of Oddi muscle rings, hypercholesterolemia rabbit animal model, temperature and biological function of smooth muscle tank experimental system equipment, observation of different types of potassium channel blockers on rabbit vasomotor role of the SO muscle rings, as well as their impact Paeoniflorin; observed Paeoniflorin on rabbits with hypercholesterolemia the role of SO muscle rings explore the effect of Paeoniflorin regulate the movement mechanism of rabbit sphincter of Oddi and its impact on sphincter of Oddi in rabbits with hypercholesterolemia impact.Objective:1. To investingate the regulating role of voltage-gated potassium channels (Kv), large-conductance calcium-activated potassium channel (BKCa) on sphincter of Oddi (sphincter of Oddi, SO) from rabbits muscle tension rings; study of the active ingredients of traditional Chinese medicine peony Paeoniflorin its control effect.2. Observation of triphosphate inositol (IP3) receptor antagonist on isolated rabbit sphincter of Oddi muscle tension rings effect and Paeoniflorin in vitro.3. Observed Paeoniflorin right hypercholesterolemia (hypercholestero-lemia, HC) isolated rabbits sphincter of Oddi muscle rings the impact of activities.Methods:1. Preparation of isolated rabbit sphincter of Oddi muscle rings specimens, placed on the smooth muscle perfusion bath temperature to observe the Kv channel blocker 4-aminopyridine (4-AP), BKCa channel blocker Iberiotoxin (IBTX) on isolated rabbit SO muscle rings contraction effect; observed Paeoniflorin pairs of 4-AP and BKCa contraction effects.2. The organ-bath was used to observe the contractile activity of isolated smooth muscle from rabbit sphincter of Oddi muscle rings after cumulatively administrated different concentration of Paeoniflorin (PA), the effect of accumulated PA on SO muscle rings in pre-constricted with acetylcholine (Ach) was observed. And to explore the mechanism, the SO muscle rings were incubated with Ca2+-free medium alone, or Ca2+-free medium plus heparin before pre-contraction with Ach.3. New Zealand white rabbits with big ears, pure 16 were randomly divided into two groups:control group (CON), and hypercholesterolemia model group (HC) of 8, CON group were fed with standard fodder, HC group were fed with hypercholesterol diet, were fed for 8 weeks. SO groups were prepared to take away from the body into muscle rings, placed on the smooth muscle perfusion bath temperature to observe the cumulative concentration of Paeoniflorin on the SO muscle rings of reaction.Results:1.①Kv channel blocker 4-AP can cause SO muscle rings; with the 4-AP concentrations increase in degree of contraction increased; BKca channel blocker IBTX can also be caused by SO muscle rings; with the BKCa increasing concentration, contraction was also enhanced degree of.②4-AP and the BKca right SO muscle ring contraction can be inhibited Paeoniflorin.2. When the concentration of PA was cumulated to (12.5,25,50,100)μmol/L, it caused concentration-dependent relaxation while SO muscle rings were pre-constricted with Ach (10-6mol/L). This effect was not inhibited by Ca2+-free medium. However, the effect was attenuated by the co-incubation with heparin and Ca2+-free medium [without heparin: (74.56±1.47)% vs (92.31±0.84)%, with heparin:(95.98±0.52)%vs (95.03±0.43)%].3. When the concentration of Paeoniflorin was accumulated to (100nmol/L, 1μmol/L, 10μmol/L, 100μmol/L), the right HC group SO muscle rings was caused concentration-dependent relaxation (P<0.01).Conclusion:In this study, the first time, observed under in vitro conditions, the different types of potassium channel blockers on rabbit SO muscle rings relaxation effects and their impact Paeoniflorin; and further observed Paeoniflorin on HC rabbits the role of SO muscle rings the impact of the results found that:1. In vitro conditions:①Kv channel and BKca channel in the maintenance of sphincter of Oddi resting membrane potential of cells, play a major role.②Paeoniflorin of Kv channels and possibly through the regulation of BKCa channels to achieve sphincter of Oddi relaxation cells.2. The results indicate that Paeoniflorin can relax the rabbit SO muscle rings in vitro. The mechanism may include the inhibition of intracellular calcium ions release by the 1,4,5-triposphate inositol-receptor-dependent pathway in SO muscle cells.3. In vitro conditions, the observed Paeoniflorin right hypercholestero-lemia rabbits sphincter of Oddi muscle rings have a relaxing effect, what the specific mechanism remains to be further studied. |
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