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实验用白色家兔,体重2.5~3.5公斤,以7mg/kg 体重的大肠杆菌内毒素静脉注入形成内毒素休克模型。观察了注内毒素后血浆β-葡萄糖醛酸苷酶(β—g)的动态变化及654—2对其影响。结果表明,注内毒素后1小时家兔血浆β—g 明显增高,2~4小时达高峰。内毒素休克犬和大鼠的测定也得到类似结果。设想在内毒素休克时溶酶体酶大量释放入血,可能在休克发病学中起着重要作用。654—2可明显抑制家兔血浆β—g,减轻内毒素所致的低血压,并使动物存活时间明显延长。设想,654—2抑制β—g可能是其抗休克作用的一个环节。体外实验还表明,654—2可抑制 Zymosan 刺激 PMNs 释放β—g。且呈剂量反应关系。654—2的这个作用,可被 H_2受体阻断剂所拮抗。设想,654—2的这个作用可能与 H_2 受体有关。溶酶体在循环休克中的作用,巳引起广泛注意。近来有人认为,内毒素休克早期血液动力学变化是由组胺介导的。而后期不可逆休克则与溶酶体酶的大量释放及心肌抑制因子(MDF)产生有关。654—2对感染性休克有明显抗休克作用,这种抗休克作用是否与其对溶酶体的影响有关呢?为此,我们观察了654—2对内毒素休克家兔血压和血浆溶酶体酶活力的影响,并观察654—2对 Zymosan 所致多形核白细胞(PMNs)释放β—g 的影响。试图进一步阐明654—2抗休克作用原理。
Experimental white rabbits weighing 2.5-3.5 kg were injected intravenously with E. coli endotoxin of 7 mg / kg body weight to form an endotoxic shock model. The dynamic changes of plasma β-glucuronidase (β-g) after endotoxin injection and the effect of 654-2 on it were observed. The results showed that 1 hour after injection of endotoxin in rabbits plasma β-g was significantly increased, 2 to 4 hours reached its peak. Similar results were obtained with endotoxin shock dogs and rats. It is hypothesized that the release of lysosomal enzymes into the bloodstream during endotoxic shock may play an important role in the pathogenesis of shock. 654-2 can significantly inhibit the rabbit plasma β-g, reduce endotoxin-induced hypotension, and significantly prolonged animal survival. It is hypothesized that inhibition of β-g by 654-2 may be a link in its anti-shock effect. In vitro experiments also showed that 654-2 can inhibit Zymosan stimulated PMNs release β-g. And dose-response relationship. This effect of 654-2 can be antagonized by H 2 receptor blockers. It is hypothesized that this effect of 654-2 may be related to H 2 receptors. The role of lysosomes in circulating shock has drawn wide attention. It has recently been suggested that early hemodynamic changes in endotoxic shock are mediated by histamine. The late irreversible shock is associated with the release of massive amounts of lysosomal enzymes and the production of cardiac myostatin (MDF). 654-2 has a significant anti-shock effect on septic shock. Is this anti-shock effect related to its effect on lysosomes? To this end, we observed the effects of 654-2 on endotoxin shock in rabbits with blood pressure and plasma lysosomes The effect of 654-2 on the release of β-g from Zymosan-induced polymorphonuclear leukocytes (PMNs) was observed. Trying to further clarify the principle of anti-shock effect of 654-2.