柳氮磺胺吡啶和PhCL28A抑制乙醇和保泰松诱导的大鼠胃溃疡形成：内源性前列腺素未参与其中？

Sulphasalazine and PhCL28A inhibit the formation of ethanol- and phenylbutazone-induced rat gastric ulcers: lack of involvement of endogenous prostaglandins?

作者信息

Berry C N, Prouteau M, Lloyd K G

机构信息

Laboratoires d'Etudes et Recherches Synthélabo L.E.R.S., Meudon La Forêt, France.

出版信息

Br J Pharmacol. 1988 Mar;93(3):465-72. doi: 10.1111/j.1476-5381.1988.tb10300.x.

DOI:10.1111/j.1476-5381.1988.tb10300.x

PMID:2897215

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1853854/

Abstract

The effects of sulphasalazine (SZP) and PhCL28A on macroscopic lesion formation and ex vivo prostaglandin inactivation were studied in the ethanol (ETOH) and phenylbutazone (PBT) models of gastric ulcers in the rat. Prostaglandin 'synthesis' during homogenisation of the stomachs was also studied in the latter model. 2. Both PhCL28A and SZP when injected i.p. prevented the formation of ETOH- and PBT-induced gastric ulcers with ED50 values of 13 and 41 mgkg-1 (vs ETOH) and 3 and 32 mgkg-1 (vs PBT) for PhCL28A and SZP respectively. However, neither compound was active orally in the dose ranges used (up to 30 mg kg-1 for PhCL28A and 100 mg kg-1 for SZP). 3. Irrespective of the route of administration, SZP (100 mg kg-1) and PhCL28A (30 mg kg-1) produced slight but statistically significant decreases in ex vivo prostaglandin inactivation by 100,000 g cytosolic supernatants prepared from stomachs not receiving ulcerogen. When tested in vitro, PhCL28A (IC50 = 230 nM) was approximatively 480 times mor potent than SZP (IC50 = 110 microM) against rat stomach cytosolic prostaglandin inactivation. 4. Both ETOH (50%, 5 ml kg-1, orally) and PBT (200 mg kg-1, orally) significantly decreased ex vivo gastric cytosolic prostaglandin inactivation. PhCL28A (30 mg kg-1, orally or i.p.) decreased prostaglandin inactivation still further after ulcerogen treatment except when given i.p. before ETOH treatment. SZP (100 mg kg-1) had a similar effect when given orally before PBT treatment. 5. When the prostaglandin content of the stomach homogenates was used as a measure of ex vivo prostaglandin synthesis in the PBT experiments, PhCL28A 30 mg kg-' orally (but not i.p.) produced an 88% increase in prostaglandin E2 (PGE2) levels, but had no effect on 6-keto-PGF,, or thromboxane B2 formation during homogenization. SZP (100mg kg' i.p. or orally) was without effect. 6. We conclude from these results that the anti gastric ulcer activity of SZP and PhCL28A is independent of prostaglandin inactivation and endogenous prostaglandin formation is probably not involved.

摘要

在大鼠胃溃疡的乙醇（ETOH）和保泰松（PBT）模型中，研究了柳氮磺胺吡啶（SZP）和PhCL28A对宏观病变形成和离体前列腺素失活的影响。在后者模型中还研究了胃匀浆过程中前列腺素的“合成”。2. 腹腔注射PhCL28A和SZP均可预防ETOH和PBT诱导的胃溃疡形成，PhCL28A和SZP的ED50值分别为13和41mg/kg（相对于ETOH）以及3和32mg/kg（相对于PBT）。然而，在所使用的剂量范围内（PhCL28A高达30mg/kg，SZP高达100mg/kg），两种化合物口服均无活性。3. 无论给药途径如何，SZP（100mg/kg）和PhCL28A（30mg/kg）均可使未接受致溃疡剂处理的胃制备的100,000g胞质上清液离体前列腺素失活略有但具有统计学意义的降低。体外测试时，PhCL28A（IC50 = 230nM）对大鼠胃胞质前列腺素失活的效力比SZP（IC50 = 110μM）高约480倍。4. ETOH（50%，5ml/kg，口服）和PBT（200mg/kg，口服）均显著降低离体胃胞质前列腺素失活。PhCL28A（30mg/kg，口服或腹腔注射）在致溃疡剂处理后可进一步降低前列腺素失活，但在ETOH处理前腹腔注射时除外。SZP（100mg/kg）在PBT处理前口服时具有类似作用。5. 在PBT实验中，当胃匀浆中前列腺素含量用作离体前列腺素合成的指标时，PhCL28A 30mg/kg口服（而非腹腔注射）可使前列腺素E2（PGE2）水平升高88%，但在匀浆过程中对6-酮-PGF1α或血栓素B2的形成无影响。SZP（100mg/kg腹腔注射或口服）无作用。6. 我们从这些结果得出结论，SZP和PhCL28A的抗胃溃疡活性与前列腺素失活无关，可能不涉及内源性前列腺素的形成。