| Background and Objective:As a necessary treatment for modern medicine,laparotomy can treat various diseases of the digestive system and genitourinary system,with significant therapeutic effect.However,laparotomy can also cause various postoperative complications.Postoperative complications may reduce the patient's prognosis and quality of life,so to avoid postoperative complications is an important part of postoperative rehabilitation.Postoperative peritoneal adhesions(PPAs)is the most common complication of abdominal surgery,which is difficult to avoid and may lead to many adverse consequences,and is an important challenge in the field of postoperative rehabilitation.Even if the application of laparoscopic,hysteroscopic and other abdominal minimally invasive surgery to some extent to reduce the surgical trauma to the body,but the occurrence of postoperative abdominal adhesions still can not be completely avoid.Medical workers explored multiple aspects of postoperative abdominal adhesions and achieved some progress,however,there is no method has been found so far to completely prevent PPAs.Traditional Chinese medicine has the advantages of low side effect,low price and secondary injury avoidance.With the development of traditional Chinese medicine and modern medicine,Chinese medicine has shown unique advantages in the field of postoperative rehabilitation.Chinese medicine believes that the formation of PPAs is the result of the qi and blood stasis and the bowel gas stasis.Chuanxiong has the effect of promoting blood circulation and qi analgesic.As the effective component of Chuanxiong,ligustrazine has been confirmed with the effect of prevention and treatment on peritoneal adhesions.As an alkaloid,ligustrazine has the characteristics of fast metabolism,fast absorption and short half-life,resulting in low bioavailability and limiting its clinical application.The mentor team aimed at the metabolic characteristics of ligustrazine,using nanotechnology to increase drug particle solubility,and developed a new formulation of ligustrazine nanospray,combined with the covering and isolation of polylactic acid.The new formulations of nano-spray of ligustrazine has made up the disadvantage in metabolism of ligustrazine,which play an important role in the development of prevention and treatment of postoperative peritoneal adhesions.The mechanism of postoperative intra-abdominal adhesions has not yet been clarified and is currently considered to be related to oxidative stress,inflammatory response,immunoregulatory imbalance,and fibrinolysis system imbalance.Oxidative stress is an important part of the formation of intra-abdominal adhesions,and the regulation of postoperative oxidative stress may be a new target for the prevention and treatment of intra-abdominal adhesions.The Nrf2-ARE signaling pathway is an important endogenous anti-oxidative stress defense mechanism,and its induced antioxidant enzymes are of great significance for the body to exert anti-oxidation.Therefore,it is of great significance to deeply investigate the mechanism of Chinese medicine regulating Nrf2-ARE signaling pathway in preventing intra-abdominal adhesions,and to clarify the effective targets and pathways of ligustrazine nano-sprays(LNNS)in preventing and treating postoperative abdominal adhesions.Methods:1.Research of the effect of LNNS on PPAs.File method was used to establish the rat models of PPAs.24 rats were divided into sham group,model group,LNNS group and sodium hyaluronate(SH)group.The adhesion of rats was observed under microscope.The Masson staining of rat adhesion tissue was observed by microscope.The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)were detected by spectrophotometer.By enzyme linked immunosorbent assay(ELISA),the level of serum nitric oxide(NO),myeloperoxidase(MPO),serum reactive oxygen species(ROS),matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)was detected.2.The research of regulation of LNNS on Nrf2-ARE oxidative stress signal pathway.24 rats were divided into sham group,model group,LNNS group and SH group.File method was used to establish the rat models of PPAs.The protein and mRNA expression of HO-1 and Nrf2 in the nucleus of adhesion cells were detected by Western Blotting and Real time PCR.Immunohistochemistry was used to observe the nuclear translocation of Nrf2 at the adhesion site.Result:1.Comparing with the sham-operation group,the activity of SOD and the content of MDA,NO and MPO in the model group were significantly increased.2.LNNS can regulate the expression of fibrinolytic system factors TIMP-9 and MMP-9 to inhibit the formation of adhesion,and inhibit the production of ROS to correct the body's oxidative stress.3.LNNS can promote the Nrf2 protein translocation to the nucleus and activate the Nrf2-ARE pathway to increase the expression of major proteins Nrf2,HO-1 protein and mRNA.Conclusion:1.LNNS can effectively prevent and treat postoperative abdominal adhesions by correcting oxidative stress and restoring redox system balance.Its antioxidative effect may be achieved through activation of Nrf2-ARE signaling pathway and induction of its anti-oxidant protein expression.2.Traditional Chinese medicine has great potential for development in the field of postoperative rehabilitation.The in-depth research on the excavation and mechanism of TCM prescriptions and the exploration of the mechanism of action and effective targets of TCM efficacy will help improve the bioavailability and clinical targeting of TCM.3.The widespread application of the theory of "preventive treatment of disease" can help eliminate the occurrence of postoperative complications and secondary diseases and improve the prognosis and quality of life of patients. |
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