The Low Dose-dependent Effect Of L-arginine In The Treatment Of Acute Pancreatitis In Rats

ObjectiveIn the pathogenesy of AP, the theory of cytokine and inflammatory reaction has been generally accepted by everyone .Some inflammatory transmitter which mediatly causing by cytokine in AP ,can make neutrophilic leukocyte sticking and gathering in region. The cytokine and inflammatory transmitter produced by activated neutrophilic leukocyte can bring out cytotoxic effect to regional part,the changes of vasopermeability, the aggregation of blood plate, these changes can make pancreatic microcirculation disturbance, aggravating injury of pancreas.The infernal circle will induce the pancreas and peripancreatic tissue autodigestion, the cytokine produced by regional inflammatory reaction enter the blood circulation, keep on producing large cytokines ,lead to systemic effect, so the regional inflammatory reaction advancing to SIRS.The biological effects of nitric oxide changes with different concentration. Therefore, there has been a controversial question in the treatment of pancreatitis. This is related to the content of nitric oxide in the tissues. The small does of nitric oxide maintain the integrity of blood vessels, relax vascular smooth muscle, increase the perfusion of blood capillary bed and improve microcirculation. Moreover, it can still protect the capillary endothelial cells, inhibit platelet aggregation, prevent leukocyte from inhibiting vascular endothelium, so it reduces inflammation of pancreatic tissue, decrease edema. On the contrary, the large dose of nitric oxide have toxic effect for the pancreatic tissue. Thereby, nitric oxide is considered to be both a regulative and anti-inflammatory factors, and a cytotoxic inflammatory cytokines.In the human body, Nitric Oxide Synthase is the speed-limit enzyme of NO synthesis. Functionally, NOS has two forms: construction NOS (cNOS) and inducible NOS (iNOS). cNOS, under normal circumstances, can be activated and produce NO, playing their physiological function, which is mainly for the guanosine monophosphate cycle to increase cGMP and to dilate blood vessels. iNOS is a pathological enzyme, under normal conditions, being rare in the cells, but abound in certain special circumstances, such as influenced by lipopolysaccharide and cytokines, and also can maintain for a period of time. The catalysis of iNOS produce excessive NO, and possibly generate cytotoxic tissues.Arginine, a semi-essential aminoacid, is the premise of the production of NO in human bodies. Arginine can produce NO through the catalysis of NOS, and with NOS dosing function, the treatment with lower doses of L-Arg can be achieved via the following respects:â‘ Arg product NO by participating the vascular signal transduction, dilate blood vessels, reduces vascular shrinkage and the negative effects of endothelial swelling upon variable blood flow.â‘¡Arg reduces the formation of oxygen fee radicals, inactivate them, thereby reducing the negative effects of oxygen free radicals on the membrane fluidity and increasing the deformability of cells.â‘¢Arg inhibits the release and ectopic activation of trypsin, preventing positively charged macromolecules from being adhered to red blood cells and decreasing cell aggregation.â‘£NO produced in endothelial cells forms a protective layer on the surface of vascular endothelium, reducing vascular resistance and preventing the adhesion of neutrophil cells in vascular endothelium.⑤The activating expression of iNOS is reduced, and so is the production of NO under inflammation.This study investigates the small dose of L-arginine's effects in treating acute pancreatitis for experimental rats.Methods1.Iodine-amidon chromatometry to test serum amylase2.Nitrate reductase is used to determine the amount of NO2-/NO3- in pancreatic tissues3.Pancreatic tissue morphology is checked and a quantitative assessment is made about the pancreatic tissue injury.ResultsNO₂^-/NO₃^-Content: AP group>L-arg treatment group>sham group,AP group is higher than sham-operating group in serum amylase and pancreatic tissue pathology score, and it remains the same even after L-arg treatment, but to a lower degree.ConclusionAs the results show, acute pancreatitis results in the increase of NO production. After L-arg is given, No content is decreased. With its pathological damage beding reduced and the value of serum amylase declining, the small dose of L-Arg can play a role in the treatment.