摘要
Long-term exposure to bioincompatible peritoneal dialysis(PD) solutions frequently results in peritoneal fibrosis and ultrafiltration failure,which limits the life-long use of and leads to the cessation of PD therapy.Therefore,it is important to elucidate the pathogenesis of peritoneal fibrosis in order to design therapeutic strategies to prevent its occurrence.Peritoneal fibrosis is associated with a chronic inflammatory status as well as an elevated oxidative stress(OS) status.Beyond uremia per se,OS also results from chronic exposure to high glucose load,glucose degradation products,advanced glycation end products,and hypertonic stress.Therapy targeting the cannabinoid(CB) signaling pathway has been reported in several chronic inflammatory diseases with elevated OS.We recently reported that the intra-peritoneal administration of CB receptor ligands,including CB_1 receptor antagonistsand CB_2 receptor agonists,ameliorated dialysis-related peritoneal fibrosis.As targeting the CB signaling pathway has been reported to be beneficial in attenuating the processes of several chronic inflammatory diseases,we reviewed the interaction among the cannabinoid system,inflammation,and OS,through which clinicians ultimately aim to prolong the peritoneal survival of PD patients.
Long-term exposure to bioincompatible peritoneal dialysis (PD) solutions frequently results in peritoneal fibrosis and ultrafiltration failure, which limits the life-long use of and leads to the cessation of PD therapy. Therefore, it is important to elucidate the pathogenesis of peritoneal fibrosis in order to design therapeutic strategies to prevent its occurrence. Peritoneal fibrosis is associated with a chronic inflammatory status as well as an elevated oxidative stress (OS) status. Beyond uremia per se, OS also results from chronic exposure to high glucose load, glucose degradation products, advanced glycation end products, and hypertonic stress. Therapy targeting the cannabinoid (CB) signaling pathway has been reported in several chronic inflammatory diseases with elevated OS. We recently reported that the intra-peritoneal administration of CB receptor ligands, including CB1 receptor antagonists and CB2 receptor agonists, ameliorated dialysis-related peritoneal fibrosis. As targeting the CB signaling pathway has been reported to be beneficial in attenuating the processes of several chronic inflammatory diseases, we reviewed the interaction among the cannabinoid system, inflammation, and OS, through which clinicians ultimately aim to prolong the peritoneal survival of PD patients.
基金
Supported by The Ministry Of Science and Technology,Taiwan,Nos.NSC 96-2628-B-075-003-MY3,MOST 104-2314-B-075-031,and MOST 105-2628-B-075-008-MY3
Taipei Veterans General Hospital,Taipei,Taiwan,No.V106D25-003-MY3-1
Taipei Veterans General Hospital,National Yang-Ming University Excellent Physician Scientists Cultivation Program,No.103-V-B-024