Abstract
Although materials and modern surgical techniques have been developed to suppress postoperative adhesions, adhesion formation can still occur, and thus, a novel effective anti-adhesion drug is greatly needed. In the present study, we explored the efficacy of paeoniflorin treatment against postoperative peritoneal adhesions and examined the anti-oxidative stress and anti-inflammatory properties of PE. Forty-eight male Sprague-Dawley rats were randomly divided into 6 groups for the study: the sham, control, hyaluronan and three concentrations (10, 20 and 40 mg/kg/d) paeoniflorin groups. Abdominal adhesions were created by abrasion of the caecum and its opposite abdominal wall. In the paeoniflorin groups, the rats were administered daily oral doses of paeoniflorin for 7 days. The abdominal cavities of the rats were reopened with a U-shaped incision to macroscopically grade the adhesions. Histologic analysis was performed, and oxidative stress, inflammatory cytokine, collagen fiber degradation and cytokeratin levels were measured. Macroscopic and histopathological measurements revealed that paeoniflorin reduced peritoneal adhesion and inflammation. Notably, treatment with paeoniflorin reduced the protein levels of TGF-β1, IL-6 and COX-2. The collagen fiber fractions were distinctly lower in the PE groups than in the control group. Western blotting analyses showed that paeoniflorin increased MMP-9 and superoxide dismutase-2 protein expression and sharply reduced α-SMA and COX-2 protein expression. Peritoneal mesothelium cells were more continuous and complete in animals treated with paeoniflorin. Our study suggests that paeoniflorin can be used to ameliorate peritoneal adhesions via anti-oxidative stress and anti-inflammatory actions during the postoperative period.
Highlights
The incidence of adhesion formation is greater than 93% after an abdominal surgical procedure [1, 2]
We explored the efficacy of paeoniflorin treatment against postoperative peritoneal adhesions and examined the anti-oxidative stress and anti-inflammatory properties of PE
PE significantly reduces macroscopic peritoneal adhesion scores in a rat model All the rats survived to 7 days after the operation, and no significant differences were observed in the body weights of the rats among the six groups (Supplementary Figure 1)
Summary
The incidence of adhesion formation is greater than 93% after an abdominal surgical procedure [1, 2]. Few clinical doctors focus on the high incidence of peritoneal adhesion formation [3, 4] or complications, including bowel obstruction, infertility, pelvic pain and other serious conditions [5, 6]. Multiple products for the prevention of peritoneal adhesions have been marketed [7,8,9,10], including barrier materials. Peritoneal adhesion is triggered immediately after the peritoneum undergoes surgery, trauma, infection or oxidative stress [14]. Surgery and injury induce peritoneal mesothelial cell dysfunction and result in fibrinogen-rich severe extravasation, which is degraded via the process of fibrinolysis. An inflammatory response is the result of peritoneal adhesion, in addition to dysregulated fibrinolysis and collagen production [15, 16]. Studies [17, 18] in rat models have shown that the infiltration of macrophages aggravates adhesion formation by the systematic depletion of macrophages themselves
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