Morphological Changes In Network Of Interstitial Cells Of Cajal In Rat With Multiple Organ Dysfunction Syndrome

Background:Multiple organ dysfunction syndrome (MODS) is a clinical syndrome,which is induced by the primary disease, such as serious injury (including shock, acute severe pancreatitis, et al), severe infections, extensive burns, surgical and obstetric major operations and oriented from systemic inflammatory response syndrome (SIRS). In MODS there are two or more organs dysfunction simultaneously or successively. Multiple organ failure (MOF)induced by MODS remains the major cause of death in patients with abdominal surgery in current. At present, the study suggests that the gastrointestinal tract is the hub of organs in the SIRS, the device in expansion of inflammatory media, the initiation and target organ. MODS may cause damage to gastrointestinal motility, bacterial translocation and impaired intestinal epithelial barrier function.Interstitial cells of Cajal(ICC) show a highly branched morphology and form unique networks in gastrointestinal tract,which coordinate gastrointestinal motility.Two populations of ICC are known by their functions:one locate in the area of the myenteric plexus(ICC-MY),which form a network between the circular and longitudinal muscle layers, and serve as electrical pacemakers; the other in the area of the deep muscular plexus(ICC-DMP), which lie between the outer and the inner subdivisions of the circular muscle layer, and are densely innervated by excitatory and inhibitory enteric motor neurons. These ICCs form the enteric nerve-ICC-smooth muscle network associated with the varicosities of enteric motor neuron and have close association with the smooth muscle cells through gap junctions. ICC is the medium of the nerve signal conveying from the enteric nerve system to the smooth muscle in the gastrointestinal tract. As a basic functional unit of gastrointestinal motility, the network of enteric nerve-ICC-smooth muscle is considered to be related to the gastrointestinal dysfunction in many diseases.Objective:To establish the model of MODS in rats induced by bacterial peritonitis, and observe the morphological changes in the network of enteric ICC-smooth muscle cells in rats with MODS.Methods:sixty Wistar rats of both sexes weighing 200 to 250g were randomly divided into two groups:control group (n=20), Model group of MODS (n=40). The model of MODS was established according to previous study. Briefly,1.5 ml suspension of 8×10 cfu/ml of Escherichia coli strain O127H6,which contained 10% BaSO4 was injected under sterile conditions into the abdominal cavities of the rat in the MODS group. The rats of control group were injected 1.5ml normal saline. Twenty-four hours after injection, short segments of proximal jejunum were removed from alive rats in two groups.Ultrathin sections were cut and studied with transmission electron microscope.Sections were embedded in paraffind and processed according to the procedures for immunohistochemistry.Immunoreactivities to Cx43 were compared in the intestinal muscle of control and MODS rats.Results:Anatomical changes Compared with those in control group, gastrointestinal tracts were distended significantly in the rats with MODS. Serosa congestioned and swelled. Omentum bleeding spots, a large number of peritoneal exudate,and bloody ascites were observed.Most of the intestines were dark red with congestion spots.Dark red fluid was observed in lumen. Intestinal mucosa bleeded and necrosis; intestinal adhesions and peritonitis were obvious.Observation under electron microscopy Compared the ultrastructural features of ICC-DMP of the MODS group with the control group, ICC-DMP displayed severe ultrastructural abnormalities.The nuclei of ICC-DMP were shrunken.Injury was displayed in both perinuclear cytoplasm and the ICC-DMP processes.The plasma membrane bleb was observed. Compared the ultrastructural features of ICC network of the MODS group with the control group, the ultrastructural features of ICC-DMP and smooth muscle cells were severely damaged.Gap junctions and desmosomes between ICC-DMP-smooth muscle cells,ICC-DMP-ICC-DMP,smooth muscle cells-smooth muscle cells were destructed significantly.Immunohistochemistry examination Compared with the control group, immunoreactivities and mean densities of Cx43 of intestine decreased significantly in MODS group (P<0.01).Conclusions:Gross morphological observation of the gastrointestinal tracts revealed a marked intestinal distention in the rats with MODS; this distention was due to the paralysis of gastrointestinal tracts. Compared with the control group,ultrastructural features of ICC-DMP were injured in rats with MODS;ICC network of the MODS group were severely damaged.