실험적 국소 뇌허혈에서 독시싸이클린의 효과

Abstract

Background: Doxycycline, one of the tetracycline analogs, can inhibit matrix metalloproteinases as well as the leukocyte function, release of oxygen radicals from neutrophils, and inducible nitric oxide synthase, which are involved in tissue damage following cerebral ischemia. It has been reported that tetracycline analogs are effective in patients with rheumatoid arthritis and aortic aneurysm. Considering this previous evidence, doxycycline may have beneficial effects on ischemic stroke.

Methods: Adult male spontaneous hypertensive rats were anesthetized with isoflurane and subjected to 2 hour middle cerebral artery(MCA) occlusion by retrograde insertion of a nylon suture through the internal carotid artery. Animals received either intraperitoneal doxycycline(45㎎/㎏)(N=9) or normal saline(N=9) one hour before occlusion and followed by every 2 hours twice. After three hours of reperfusion, animals were decapitated and 2㎜-thick coronal slices of the brain were strained with 2,3,5 triphenyltetrazolium chloride(TTC) solution to define the area of ischemia damage. The volume of infarction was measured using the computer-assisted scannet.

Results: All subjects showed neurologic deficits after MCA occlusion. The infarcted area could be visualized well by TTC staining after three hours of reperfusion. The total infarction volume was significantly reduced in the doxycycline treatment group(12.2±2.58% of whole brain volume) than in the control group(19.5±2.13% of whole brain volume, p＜0.05).

Conclusions: Doxycycline showed a protective effect against ischemic insults in experimental MCA occlusion and reperfusion model of rats.