Anti-hypertensive Effect of Shark Liver Oil in Spontaneously Hypertensive Rats and Platelet Activated Rats

Abstract

본 연구에서는 상어간유(Shark liver oil)의 혈압증가억제 효과를 본태성 고혈압 동물 모델 (Spontaneously hypertensive rats, SHRs)을 통해 확인하였고, 그 기전을 혈소판 활성 모델 (Platelet activation model)을 통하여 규명하였다. 수컷 본태성 고혈압 흰쥐 (SHR)와 정상혈압 대조군 흰쥐(WKY)를 초기혈압수치에 따라 난괴법으로 정상혈압군 (WCON), 고혈압군 (SCON), 고혈압-상어간유 (스쿠알렌 40%) 400mg/kg B.W. (SR), 고혈압-상어간유 (스쿠알렌 98%) 400mg/kg B.W. (SEL) 그리고 고혈압-상어간유 (스쿠알렌 98%) 1,020mg/kg B.W. (SEH) 총 5그룹으로 나누었다. 8주간 경구투여로 공급하였고, 매주 수축기 혈압 변화를 관찰하였다. 상어간유 투여 6주 후부터 고용량군 (SEH)에서 혈압이 유의적으로 낮아지기 시작하여 8주까지 지속되었다. IL-1β, IL-6, TNF-α, IL-10의 염증지표가 WCON군에 비해 SCON군에서 유의적으로 증가했고, SEH군은 Model군에 비해 모든 지표에서 유의적으로 감소하였다. 이를 바탕으로 콜라겐과 에피네프린을 투여한 혈소판 활성 모델을 이용하여 결과의 경향의 유사함을 관찰하였다. 정상군 (CON), 혈소판 활성군 (Model), 혈소판 활성-상어간유 (스쿠알렌 40%) 400mg/kg B.W. (SR), 혈소판 활성-상어간유 (스쿠알렌 98%) 400mg/kg B.W. (SEL), 혈소판 활성-상어간유 (스쿠알렌 98%) 1,020mg/kg B.W. (SEH) 5그룹으로 나누었다. 4주간 경구투여로 공급하였다. IL-1β, IL-6 , TNF-α의 mRNA 발현이 CON군에 비해 Model군에서 유의적으로 증가하였고, SEH군이 Model군에 비해 유의적으로 감소하였다. 항산화 지표인 ROS 수치 또한 CON군에 비해 Model군에서 유의적으로 증가하였고, 모든 시료군에서 Model군에 비해 유의적으로 감소하였다. 이러한 결과에서, 스쿠알렌은 혈압을 낮추어 고혈압을 개선시킬 가능성이 있는 것으로 나타났는데, 이는 항염증 반응에 의한 것으로 사료된다. 따라서, 스쿠알렌 섭취에 따른 혈압 저하 효과는 고혈압 예방 및 혈압 조절을 위한 식품소재로서의 기능을 보여주었다. 그러나 항염증-항산화 관련 기전에 대한 추가연구가 필요하며, 더 나아가 사람을 대상으로 한 임상시험도 수행되어야 할 것이다.;Hypertension is one of the most important variable risk factor for coronary heart disease, congestive heart failure, stroke, chronic kidney disease, and peripheral vascular disease. Many emerging signal might have a potential to regulate blood pressure by numerous mechanisms. This study examined the antihypertensive effects of Squalene in in vivo and in vitro study. In first study, male spontaneously hypertensive rats (SHRs; six-week old, n=40) and normotensive Wistar-Kyoto rats (WKYs; six-week old, n=10) were randomly divided in 5 groups (n=10/group); untreated control group, SL treatment group (400 mg/kg body weight); and SH treatment groups (400 and 1,020 mg/kg body weight). WKY rats (n=10) were used as an untreated control group. They were given by oral gavage for 8 weeks and their blood pressure was recorded weekly. Blood pressure was significantly reduced in SEH group compared to the SCON group from 6 weeks to 8 weeks (p<0.05). Inflammation level (IL-1β, IL-6, TNF-α and IL-10) of SCON group was found to be significantly increased compared with WCON group. SR, SEH groups were significantly decreased compared with SCON group in some markers. SEL groups were significantly decreased compared with SCON group in all markers. In second study, male Sprague Dawley (SD, four-week old) rats were randomly assigned into six groups to treat as follows for four weeks (n=8 per group): saline/saline (normal control), saline/collagen-epinephrine (CE) (platelet activated control), SL (400 mg/kg body weight)/CE, SH (400 and 1,020 mg/kg body weight)/CE. The mRNA expression of inflammation level (IL-1β, IL-6 and TNF-α) of Model group was found to be significantly increased compared with CON group. SHE group were significantly decreased compared with Model group in all markers. In IL-1β, all treatment groups were significantly decreased compared with Model group. ROS level in Model group was significantly higher than CON group. The ROS level showed significantly decreased in all treatment groups compared with the Model group. Taken together, the results provide a basis for the use of SLO in regulating blood pressure in inflammatory mechanism.