| Adhesion is a common post-surgical complications, whose mechanism is associated with organizations ischemia, injury, local over-stimulated inflammatory response caused by foreign bodies and the reduced fibrinolytic activity. Tumor necrosis factor alpha (TNF -α), interleukin (IL), transforming growth factor beta 1 (TGF-β1) and other cytokines play important roles in the regulation of adhesion formation. Although many drugs have protective effect on the formation of intestinal adhesion after abdominal surgery, there was not yet a satisfactory drug for clinical use, therefore the development of new drugs to combat intestinal adhesion has important clinical significance.For further development and application, the subjects studied protective effect of Rhein-arginine (RhA) on postoperative intestinal adhesion in rats and explored its mechanism. Experiment was divided into three parts:1. Protective effect of RhA on postoperative intestinal adhesion in ratsSD male rats were randomly divided into 6 groups: normal control group, model group, positive control group and RhA low, medium and high dose (7.5 mg·kg-1, 15 mg·kg-1, 30 mg·kg-1) group. In addition to the normal control group, the remaining groups were prepared intestinal adhesion model. Normal control group and model group, were given normal saline by intraperitoneal injection of 0.5ml·100g-1, positive control group by intraperitoneal injection of dexamethasone sodium phosphate 10 mg·kg-1, RhA low, medium and high dose group by intraperitoneal injection of different concentration RhA, continuous administration of 1 week, once a day. Rats were killed at 8th day, the degree of adhesion grade was observed. At the same time the cecum and abdominal wall incision organizations were taken out for determination of hydroxyproline (Hyp) content, so did the histological observation. The results showed that RhA can significantly reduce the degree of intestinal adhesion in rats, inhibit the proliferation of fibrous connective tissue, reduce the Hyp contents of cecal, but there was no effect on Hyp content in the abdominal wall. All of these indicate that RhA can prevent the formation of postoperative intestinal adhesion and do not interfere with the normal organizations healing process.2. Anti-inflammatory mechanism of RhA in preventing the postoperative intestinal adhesion formationAcetic acid induced acute peritonitis model was established in mice. Then absorbance values of Evans blue in peritoneal exudates were observed. In the results high, medium-dose RhA could significantly reduce the absorbance values (P <0.05), which indicated that RhA could inhibit increased vascular permeability and reduce the exudation at acute phase. Cotton ball granuloma model was established in rats, then the weight of cotton ball granuloma was observed , resulting in high-, medium- and low-doses RhA can significantly reduced the weight of cotton ball granuloma (P <0.05 or P <0.01), which indicated RhA could inhibit proliferation of fibrous connective tissue. An experimental intestinal adhesion model was established in rats, then the content of TNF-α, IL-1β, IL-4 in serum was observed. Compared with the model group, the results showed that, the content of TNF-α, IL-1βin RhA high-, medium-dose group were significantly lower. Content of IL-4 in all RhA group was not different with that in model group. According to the above results, it can be concluded that RhA achieve the role of prevention of postoperative intestinal adhesion by reducing vascular permeability, reducing seepage, inhibiting connective tissue proliferation and suppression of excessive expression of inflammatory factors .3. Effect of RhA on the fibrinolytic system in rats with postoperative intestinal adhesionExperimental intestinal adhesion model was established in rats, and then the activity of t-PA and PAI in plasma was measured by chromogenic substrate assay, content of TGF-β1 in tissues were analyzed by immunohistochemistry method. The results showed that, each group of RhA can significantly reduce the activity of PAI in plasma (P <0.05), increase t-PA activity (P <0.05). Compared with model group, high, medium-dose RhA decreased the expression of TGF-β1 significantly, the positive control group and RhA low-dose group had no effect on TGF-β1 expression.To sum up, RhA can prevent the formation of postoperative intestinal adhesion by two ways:①reducing vascular permeability, reducing seepage, inhibiting connective tissue proliferation and suppression of excessive expression of inflammatory cytokines;②reducing the expression of TGF-β1, inhibiting increased activity of PAI, increasing t-PA activity. In result the activity of plasminogen is enhancing, the fibrinogen effusion is dissolved.
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