Poisner Alan, Bass Devin, Fletcher Amanda, Jain Ashwin, England Janessa Pennington, Davis Mariah Gawlik, Arif Dauod, Molteni Agostino
a 1 Department of Pharmacology , University of Kansas Medical Center, Kansas City, KS, USA.
b Pharmacology , University of Kansas Medical Center , Kansas City , KS, USA.
Exp Lung Res. 2018 Sep;44(7):361-367. doi: 10.1080/01902148.2018.1552339. Epub 2019 Jan 13.
In a model of fat embolism using triolein-treated rats, we have reported that the acute pulmonary histopathological changes at 48 hrs were ameliorated by the angiotensin AT1 receptor blocker losartan, the angiotensin converting enzyme inhibitor captopril, and the direct renin inhibitor aliskiren. Although much of the pathology had declined by 3 weeks, the changes persisted at 6 weeks. The purpose of the study was to extends the time course investigation to 10 weeks and to examines whether the fat embolism effects continue to be blocked by losartan when given at a late time period.
Unanesthetized rats were challenged with i.v. triolein or saline. After 6 weeks, one group received saline or losartan i.p. and the losartan group also received losartan in the drinking water. At 10 weeks, the experiment was terminated.
Confirming previous results, the fat embolism group showed normal weight gain at 6 weeks without apparent distress and also appeared normal at 10 weeks. However, at 10 weeks the lungs showed inflammatory and fibrotic changes that were greater than those found at 6 weeks. These changes were reduced by losartan.
These findings show that the effects of fat embolism continue to progress to 10 weeks after the initial insult with triolein. The fact that the protective effects of losartan treatment started at 6 weeks supports the involvement of the renin-angiotensin system in late as well as early stages of the histopathological changes following fat embolism. It also supports the use of angiotensin blockade in clinical situations even long after an initial trauma where fat embolism is suspected.
在使用三油酸甘油酯处理大鼠的脂肪栓塞模型中，我们已报道血管紧张素AT1受体阻滞剂氯沙坦、血管紧张素转换酶抑制剂卡托普利和直接肾素抑制剂阿利吉仑可改善48小时时的急性肺组织病理学变化。尽管大部分病理变化在3周时已有所减轻，但在6周时这些变化仍持续存在。本研究的目的是将时间进程研究延长至10周，并检查在晚期给予氯沙坦时，脂肪栓塞的影响是否继续被其阻断。
对未麻醉的大鼠静脉注射三油酸甘油酯或生理盐水。6周后，一组腹腔注射生理盐水或氯沙坦，氯沙坦组还在饮用水中添加氯沙坦。10周时，终止实验。
证实先前的结果，脂肪栓塞组在6周时体重正常增加，无明显不适，10周时也看起来正常。然而，在10周时，肺显示出比6周时更严重的炎症和纤维化变化。这些变化被氯沙坦减轻。
这些发现表明，脂肪栓塞的影响在最初受到三油酸甘油酯损伤后持续发展至10周。氯沙坦治疗的保护作用在6周时开始这一事实支持肾素-血管紧张素系统参与脂肪栓塞后组织病理学变化的早期和晚期阶段。这也支持在怀疑有脂肪栓塞的初始创伤后很长时间的临床情况下使用血管紧张素阻断治疗。
