Protective effects of thromboxane synthetase inhibitors in rats in endotoxic shock.
Protective effects of thromboxane synthetase inhibitors in rats in endotoxic shock.
复制标题
血栓素合成酶抑制剂对内毒素休克大鼠的保护作用。
DOI：
10.1161/01.res.46.6.854
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发表时间：
1980
影响因子：
20.1
通讯作者：
D. Knapp
中科院分区：
文献类型：
--
作者：
W. C. Wise;J. Cook;P. Halushka;D. Knapp
为了评价血栓烷（Tx）在内毒素休克中的致病作用，评估了Tx合成酶抑制剂7-（1-咪唑基）庚酸（7-IHA）在大鼠中的潜在保护作用，并与咪唑进行了比较。7-在沙门氏菌内毒素（20 mg/kg，iv）之前30分钟iv给予IHA（30 mg/kg）可将溶媒处理大鼠的存活率从5小时时的42%（n = 24）提高至100%（n = 11）。到24小时，仅8%的溶剂处理的大鼠存活，而80%的处理组存活。如果在内毒素（20 mg/kg，iv）前30分钟iv给予7-IHA（30 mg/kg），则不会发生静脉血浆血栓素B2升高。然而，7-IHA不能抑制内毒素诱导的血浆前列腺素E升高。内毒素诱导溶媒处理大鼠的血小板计数从780 ± 64 × 10 3 /mm 3显著降低至179 ± 18 × 10 3 /mm 3（n = 6，P< 0.01），而咪唑预处理组血小板计数显著减少至402 ± 55 × 103/mm 3 7-IHA预处理组血小板计数为541 ± 91 × 103/mm 3（n = 5，P < 0.05）。内毒素休克时纤维蛋白原/纤维蛋白降解产物显著升高（P < 0.01），咪唑和7-IHA均显著降低（P< 0.05）。咪唑和7-IHA预处理可防止内毒素休克中溶酶体的不稳定性，如血清酸性磷酸酶和figlucuronidase的升高显著降低所示。同样，通过血清谷草转氨酶和谷丙转氨酶升高降低评估，肝细胞损伤明显减轻。这些结果与TxA 2在内毒素休克发病机制中起重要作用的假设一致。CircRes 46：854-859，1980
SUMMARY To evaluate the pathogenic role of thromoboxane (Tx) in endotoxic shock, the potential protective effects of the Tx synthetase inhibitor, 7-(l-imidazolyl)-heptanoic acid (7-IHA) was assessed and compared to that of imidazole in the rat. 7-IHA (30 mg/kg) administered iv 30 minutes prior to Salmonella enteritidis endotoxin (20 mg/kg, iv) improved the survival rate from 42% (n = 24) at 5 hours in the vehicle-treated rats to 100% (n = 11). By 24 hours, only 8% of the vehicle-treated rats survived, whereas 80% of the treated group survived. Venous plasma thromboxane B2 elevation did not occur if 7-IHA (30 mg/kg) was administered iv 30 minutes prior to endotoxin (20 mg/kg, iv). However, 7-IHA did not inhibit endotoxin-induced elevations in plasma prostaglandin E. Endotoxin induced a significant reduction in the platelet counts in vehicle-treated rats from 780 ± 64 x 10 3 /mm 3 to 179 ± 18 x 10 3 /mm 3 (n = 6, P< 0.01) by 15 minutes, whereas, in imidazole-pretreated rats, the platelet count fell significantly less to 402 ± 55 x 10 3 /mm 3 (n = 6, P < 0.05), and in the 7-IHA-pretreated rats, the platelet count fell to 541 ± 91 x 10 3 /mm 3 (n = 5, P < 0.05). Fibrinogen/fibrin degradation products were significantly increased (P < 0.01) in response to endotoxic shock, but both imidazole and 7-IHA significantly decreased (P< 0.05) this elevation. Imidazole and 7-IHA pretreatment prevented lysosomal labilization in endotoxic shock as denoted by significantly decreased elevations in serum acid phosphatase and figlucuronidase. Similarly, reduction in hepatic cellular damage, as assessed by decreased elevations of serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase, was apparent. These results are consistent with the hypothesis that TxA2 plays a significant role in the pathogenesis of endotoxic shock. Circ Res 46: 854-859, 1980