Banerjee A K, Peters T J
Department of Clinical Biochemistry, King's College Hospital, London.
Gut. 1990 Dec;31(12):1358-64. doi: 10.1136/gut.31.12.1358.
We have validated an established animal model of acute inflammatory bowel disease in indomethacin-treated rats. Studies in both in vitro and in vivo 51chromium-labelled ethylenediamine tetra-acetate (51Cr-EDTA) permeability and tissue myeloperoxidase activity, a marker of inflammatory cell invasion, showed increased permeability and enzyme levels, respectively, in treated animals compared to controls (in vitro 51Cr-EDTA permeability: (mean (SE] control 0.10 (0.02) microliter/mg per tissue, experimental 0.17 (0.02) (p < 0.01, 2 way analysis of variance); in vivo 51Cr-EDTA permeability: control 3.9 (1.3) (% dose recovered), experimental 12.1 (1.5) (p < 0.01); tissue myeloperoxidase: control 10.8 (0.4) mU/mg, experimental 17.2 (0.5) p less than 0.01). Pretreatment or simultaneous treatment of indomethacin-treated animals with glucocorticoids, sulphasalazine, or tetracycline reduced the permeability changes and the tissue inflammatory response (in vitro 51Cr-EDTA permeability: (mean (SE] sulphasalazine + indomethacin 0.11 (0.2) microliter/mg tissue (p < 0.01), prednisolone +/- indomethacin 0.12 (0.02) (p < 0.01), tetracycline + indomethacin 0.12 (0.02) (p < 0.01]. Glucocorticoids and sulphasalazine, but not tetracycline, administered after the indomethacin also partially corrected the permeability and inflammatory changes induced by indomethacin (in vitro 51Cr-EDTA permeability: sulphasalazine 0.15 (0.02) microliter/mg, p < 0.02; prednisolone 0.12 (0.02) microliter/mg, p < 0.01). This approach was used to investigate the effects of two different thromboxane synthetase inhibitors in indomethacin-treated animals. Simultaneous treatment with thromboxane synthetase inhibitors and indomethacin prevented the 51Cr-EDTA permeability and tissue myeloperoxidase increases induced by indomethacin alone (in vitro 51Cr-EDTA permeability: thromboxane synthetase inhibitors + indomethacin 0.11 (0.01) microliter/mg (p0.01); tissue myeloperoxidase: 11 (0.4) mU/mg, (p < 0.01). Thromboxane synthetase inhibitors administered after the indomethacin also partially corrected the permeability and inflammatory changes induced by indomethacin (in vitro 51Cr-EDTA permeability: thromboxane synthetase inhibitors 0.12 (0.02) mU/mg (p < 0.01); tissue myeloperoxidase 13.8 (0.5) (p < 0.01). These studies indicate that thromboxane synthetase inhibitors partially correct the intestinal lesion non-steroidal anti-inflammatory drug enteropathy and may therefore be of use in inflammatory bowel diseases in humans.
我们已验证了一种既定的急性炎症性肠病动物模型，该模型采用吲哚美辛处理大鼠。对体外和体内51铬标记的乙二胺四乙酸（51Cr - EDTA）通透性以及组织髓过氧化物酶活性（炎症细胞浸润的标志物）的研究表明，与对照组相比，处理组动物的通透性和酶水平分别升高（体外51Cr - EDTA通透性：（均值（标准误）对照组为0.10（0.02）微升/毫克组织，实验组为0.17（0.02）（p < 0.01，双因素方差分析）；体内51Cr - EDTA通透性：对照组为3.9（1.3）（%剂量回收），实验组为12.1（1.5）（p < 0.01）；组织髓过氧化物酶：对照组为10.8（0.4）mU/毫克，实验组为17.2（0.5），p小于0.01）。用糖皮质激素、柳氮磺胺吡啶或四环素对吲哚美辛处理的动物进行预处理或同时处理，可降低通透性变化和组织炎症反应（体外51Cr - EDTA通透性：（均值（标准误）柳氮磺胺吡啶 + 吲哚美辛为0.11（0.2）微升/毫克组织（p < 0.01），泼尼松龙 ± 吲哚美辛为0.12（0.02）（p < 0.01），四环素 + 吲哚美辛为0.12（0.02）（p < 0.01））。在吲哚美辛给药后给予糖皮质激素和柳氮磺胺吡啶，但不包括四环素，也可部分纠正吲哚美辛诱导的通透性和炎症变化（体外51Cr - EDTA通透性：柳氮磺胺吡啶为0.15（0.02）微升/毫克，p < 0.02；泼尼松龙为0.12（0.02）微升/毫克，p < 0.01）。该方法用于研究两种不同的血栓素合成酶抑制剂对吲哚美辛处理动物的影响。同时给予血栓素合成酶抑制剂和吲哚美辛可防止单独使用吲哚美辛诱导的51Cr - EDTA通透性增加和组织髓过氧化物酶升高（体外51Cr - EDTA通透性：血栓素合成酶抑制剂 + 吲哚美辛为0.11（0.01）微升/毫克（p0.01）；组织髓过氧化物酶：为11（0.4）mU/毫克，（p < 0.01））。在吲哚美辛给药后给予血栓素合成酶抑制剂也可部分纠正吲哚美辛诱导的通透性和炎症变化（体外51Cr - EDTA通透性：血栓素合成酶抑制剂为0.12（0.02）mU/毫克（p < 0.01）；组织髓过氧化物酶为13.8（0.5）（p < 0.01））。这些研究表明，血栓素合成酶抑制剂可部分纠正非甾体抗炎药肠病的肠道病变，因此可能对人类炎症性肠病有用。
