Ligustrazine nanoparticles nano spray’s activation on Nrf2/ARE pathway in oxidative stress injury in rats with postoperative abdominal adhesion

Abstract

Background: Postoperative abdominal adhesions formation is considered a significant clinical entity implicating the healing process following major pelvic and abdominal surgery, with serious clinical complications and need for substantial health care expenditures. However, setting a physical barrier between the damage site and the neighboring tissues is a convenient and highly valid way to minimize or prevent peritoneal adhesions. The present experimental study evaluated the preventive effect of ligustrazine nanoparticles nano spray (LNNS) on postoperative abdominal adhesion in rats and explored its mechanism.Methods: Sixty male Sprague Dawley (SD) rats were randomly divided into sham operation group, control group, sodium hyaluronate group and low, medium, and high dose LNNS groups. All groups were prepared with abdominal adhesion models except for the sham operation group. The models were made by opening the abdominal cavity to and filing the serosa in ileocecal junction. The abdominal cavity of rats in the sham operation group were only opened and sutured. The wound surface of rats in the sodium hyaluronate group, low, medium, and high dose LNNS groups were sprayed with sodium hyaluronate gel (0.5 mL/kg) and LNNS (2.5, 5, and 10 mL/kg). Rats in each group were sacrificed 7 days later. Degree of adhesion was evaluated by naked eyes and the pathological sections were scored afterwards. The collagen synthesis in adhesion tissues was detected by Masson's trichrome stain, and the activities of reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) in peritoneal fluid were detected with the method of chromogenic substrate. Levels of TNF-α and IL-1β in serum, and the protein levels of MCP-1 and MMP-9 in adhesion tissues were detected by ELISA and. immunohistochemistry respectively. RT-PCR and Western blot were utilized to identify the expression levels of Nrf2, heme-oxygenase-1, NQO1 mRNA and protein in adherent intestinal tissues.Results: Compared with the control group, the incidence of postoperative abdominal adhesions decreased in the low, medium and high dose LNNS groups, while the expression of SOD in the peritoneal fluid significantly increased. The expression levels of ROS, MDA and NO were reduced remarkably (P<0.05), so were the expression levels of serum TNF-α and IL-1β (P<0.01) and the expression of MCP-1 protein in adhesion tissues. The MMP-9 protein expression, and Nrf2, heme-oxygenase-1, NQO1 mRNA and protein expressions increased.Conclusions: LNNS with medium or high dose can significantly reduce the incidence of postoperative abdominal adhesions, the mechanism of which may be the activation of Nrf2/ARE pathway, resulting in the up-regulation of Nrf2, heme-oxygenase-1, NQO1 and mRNA expression, as well as the levels of TNF-α Yan et al. LNNS ameliorates postoperative peritoneal adhesion formation

A randomized trial of negative pressure wound therapy technology combined with intermittent instillation in the treatment of neck anastomotic leakage after esophageal cancer surgery

“…Traditional treatments for neck anastomotic leakage tend to cause a low oxygen environment around the wound's tissue, affecting the growth of new granulated tissue and delaying the wound healing cycle (25). For wound healing, oxygen pressure is the main control factor for sterilization, anti-infection, collagen synthesis, vascular hair and epithelial tissue formation (26). In the case of hypoxia, some or even all pathophysiological processes are affected.…”

Application of Traditional Chinese Medicines in Postoperative Abdominal Adhesion

“…In addition, Changtong oral liquid, a Chinese medicine compound in Nanfang Hospital, exerts a protective effect in postoperative intestinal adhesion by modulating the activity of the fibrinolysis system [101]. Ligustrazine nanoparticles nano spray can significantly reduce the incidence of PAA, which may be the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-an antioxidant response element (ARE) signaling pathway [6].…”

“…PAA refers to the pathological connection between the omentum, abdominal organs, and abdominal wall after surgery. e formation of PAA is a complex process that involves immune activation, inflammatory response, fibrinolysis imbalance, oxidative stress, collagen deposition, peritoneal tissue repair, and other biochemical events [2,6]. Abdominal surgery injury stimulates immune activation and inflammation response immediately.…”

Design and Comprehensive Characterization of Tetramethylpyrazine (TMP) for Targeted Lung Delivery as Inhalation Aerosols in Pulmonary Hypertension (PH): In Vitro Human Lung Cell Culture and In Vivo Efficacy

“…This antioxidant was shown to penetrate the skin when formulated for transdermal drug delivery for Alzheimer's treatment [20]. In addition, it has been shown to act as a Nrf2 activator (i.e., activates the Nrf/ARE pathway) in oxidative stress injury in vivo in rats [21]. Ligustrazine's antioxidant effects on lung fibrosis and ROS-related autophagy in an in vivo lung fibrosis model has been reported [22].…”