Publications
Detailed Information
Effects of fimasartan, one of angiotensin receptor blockers, on tissue damages and inflammation after focal ischemia in rat brain : 안지오텐신 수용체 차단제의 하나인 피마살탄이 백서의 국소 뇌허혈에 의한 조직손상과 염증반응에 미치는 영향
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 윤병우 | - |
dc.contributor.author | 김치경 | - |
dc.date.accessioned | 2017-07-14T01:33:17Z | - |
dc.date.available | 2017-07-14T01:33:17Z | - |
dc.date.issued | 2016-02 | - |
dc.identifier.other | 000000131848 | - |
dc.identifier.uri | https://hdl.handle.net/10371/122093 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과 뇌신경과학전공, 2016. 2. 윤병우. | - |
dc.description.abstract | Background and Purpose: Fimasartan is a newly developed angiotensin receptor blocker (ARB), and evidences suggests that fimasartan may have protective effects during myocardial infarction or atherosclerosis. However, the application of regular-dose ARBs during ischemic stroke should be used cautiously (due to lessons learned from other ARBs). In this context, we investigated the effects of low-dose fimasartan on tissue damage and inflammation after focal ischemia in rat brain.
Materials and Methods: To evaluate anti-inflammatory effects of fimasartan, oxygen-glucose deprivation (OGD) was applied in cultured astrocytes and fimasartan was treated. In in vivo experiments, noninvasive blood pressure monitoring was performed in Sprague-Dawley rats which fimasartan or phosphate-buffered saline (PBS) were administered for 4 weeks. A low-dose (0.5 mg/kg) and regular doses (1 or 3 mg/kg) of fimasartan was administered intraorally for 4 weeks, and we induced ischemia-reperfusion injury in rats. Infarct volume and the number of TUNEL-positive apoptotic cells were measured at 7 days. Functional outcomes were evaluated by modified limb placing test. To identify the anti-inflammatory effect of fimasartan, the number of inflammatory cells (OX6-positive cells) was measured. To evaluate inflmmatory makers, IkB and cyclooxygenase-2 (COX-2) were measured via Western blot analyses at 48 hours. Especially for low-dose fimasartan (0.5 mg/kg), the effects of post-treated fimasartan on infarct volume was also evaluated. Results: During OGD, fimasartan reduced the inflammatory markers in astrocytes: nuclear translocation of NF-κB, degradation of IκB, and expression of COX-2. After the administration of low-dose (0.5 mg/kg) fimasartan, blood pressure did not decrease compared to the phosphate-buffered saline (PBS)-control with MCA occlusion (MCAO) group. The infarct volume and ischemic cell death were reduced in the low-dose fimasartan-treated group (46 ± 41 for 0.5 mg/kg and 153 ± 47 mm3 for PBS-control with MCAO | - |
dc.description.abstract | P < 0.01) but not in the regular-dose groups. Low-dose fimasartan treatment improved functional recovery after ischemia and significantly decreased mortality. In our study, fimasartan reduced the degradation of IκB (whose degradation is a marker for NF-κB activation) and the formation of an inflammatory end-product, COX-2. As a result, the recruitment of inflammatory cells in the peri-infarct area decreased after low-dose, long-term treatment. After induction of transient MCAO, low dose fimasartan (0.5 mg/kg) was administerd for 3 days per oral route. The infarct volume at 3 days after MCAO decreased significantly in low-dose post-treated group compare to PBS-control with MCAO (110.8 ± 46.1 versus 162.7 ± 42.3 mm3 | - |
dc.description.abstract | P < 0.05).
Conclusion: We have demonstrated that low-dose, long-term fimasartan pre-treatment improved outcomes after focal ischemia in the brain via a reduction of inflammation. These low-dose fimasartan may have beneficial effects on tissue damage in post-treatment after MCAO. | - |
dc.description.tableofcontents | Introduction 1
Materials and Methods 4 Results 13 Discussion 27 References 31 Abstract in Korean 38 | - |
dc.format | application/pdf | - |
dc.format.extent | 1024715 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | 뇌졸중 | - |
dc.subject | 염증 | - |
dc.subject | 안지오텐신 수용체 차단제 | - |
dc.subject.ddc | 610 | - |
dc.title | Effects of fimasartan, one of angiotensin receptor blockers, on tissue damages and inflammation after focal ischemia in rat brain | - |
dc.title.alternative | 안지오텐신 수용체 차단제의 하나인 피마살탄이 백서의 국소 뇌허혈에 의한 조직손상과 염증반응에 미치는 영향 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Chi Kyung Kim | - |
dc.description.degree | Doctor | - |
dc.citation.pages | 47 | - |
dc.contributor.affiliation | 의과대학 의학과 | - |
dc.date.awarded | 2016-02 | - |
- Appears in Collections:
- Files in This Item:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.