Role of prostacyclin on microcirculation in endotoxin-induced gastroprotection in rats: a microdialysis study.
Numerous mechanisms relating to lipopolysaccharide- (LPS) induced gastroprotection have been proposed. The prostaglandin (PG) system is a promising candidate that has received considerable attention. However, the role of prostacyclin (PGI2) remains unclear. Adult, male Sprague-Dawley rats were divided into four groups: (1) control, n = 6; (2) LPS (LPS, 10 mg/kg, i.v.), n = 7; (3) LPS + indomethacin (Indo) (LPS, 10 mg/kg and indomethacin 5 mg/kg, i.v.), n = 7; and (4) Indo (indomethacin 5 mg/kg, i.v.), n = 7. Additionally, gastric microcirculation was investigated using in vivo microscopy. Tissue malondialdehyde (MDA) and glutathione levels were measured at the conclusion of the experiment. Specifically, microdialysis was used to measure the 6-keto-PGF1alpha, a stable metabolite of PGI2, while flow cytometry was used to measure the CD11b/CD18 expression of circulating neutrophils. Compared with LPS alone, LPS with Indo significantly impaired gastric microcirculation and systemic hemodynamics. LPS-induced gastroprotection was lost, as evidenced by the increased adherent leukocyte count, decreased flow velocity in the post-capillary venules, and increased tissue MDA production. Meanwhile, the luminal glucose and protein contents that comprised the gastric mucosa injury index were significantly increased. These effects of Indo are directly associated with the levels of PGI2 in gastric tissue, which increased with LPS alone and significantly decreased with a combination of LPS and Indo. This work demonstrates that PGI2 contributes to LPS-induced gastroprotection.
Ng
Chip-Jin
CJ
Department of Emergency Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
Chen
Jih-Chang
JC
Chiu
De-Fa
DF
Chen
Miin-Fu
MF
Chen
Han-Ming
HM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D011464:Epoprostenol / Q000502:physiology*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects* / Q000293:injuries; D007213:Indomethacin / Q000633:toxicity; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology*; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D011464:Epoprostenol; D007213:Indomethacin