脱毒菜籽多肽大鼠降血压试验及机理研究
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摘要
研究了脱毒菜籽多肽一次性灌胃对原发性高血压大鼠(SHR)的降血压效果。分别对空白对照组、卡托普利阳性对照组、脱毒菜籽多肽组和脱毒菜籽蛋白组的大鼠进行一次性灌胃和30 d灌胃实验,通过测定大鼠收缩压(SBP)和舒张压(DBP)变化、大鼠脏器组织ACE酶活及血清中相关生化指标含量,探究脱毒菜籽多肽的降压效果、作用器官及其降压机理。试验结果表明:一次性灌胃脱毒菜籽多肽4～12 h大鼠SBP都有显著降低(P<0.05),最大降幅24.4 mmHg出现在灌胃6 h后,对DBP仅在灌胃4～8 h时降低效果显著(P<0.05),30 d灌胃实验中血压测定于灌胃前,灌胃脱毒菜籽多肽1周能显著降低大鼠SBP和DBP(P<0.05),第4周出现最大降幅13.3 mmHg。脱毒菜籽多肽灌胃后主要作用于SHR的肺、肾和动脉抑制其ACE酶活。血清指标测定进一步表明脱毒菜籽多肽主要通过降低内皮素、肾素、血管紧张素II含量,提高NO、eNOS含量发挥降压功效。
This paper studied the reducing blood pressure activity of detoxic rapeseed peptides and the mechanism of it in mice.Control group,positive group,detoxic rapeseed peptides group and detoxic rapeseed protein group were set.The rats in each group were gavaged with captopril,detoxic rapeseed peptides and detoxic rapeseed protein in single gavaged test and 30 days gavaged test.The effect of detoxic rapeseed peptides on reducing blood pressure,its effect organs and its mechanism were detected through measuring blood pressure,measuring ACE activity in organs and content of related biochemical index in rats' serum.The maximum decrease quantity are 24.4 mm Hg and 13.3 mm Hg respectively.The results showed that gavaging detoxic rapeseed peptides could significantly reduce SBP in 2-12 h after gavageing(P<0.05),while DBP was only significantly reduced in 4-8 h during the single gavaged test(P<0.05).Detoxic rapeseed peptides can also significantly reduce rats' SBP and DBP in one week during 30 days gavaged test(P<0.05).Effect organs of detoxic rapeseed peptides are lung,kidney and artery in SHR and detoxic rapeseed peptides could decline the activity of ACE in these organs.Indexes content in serum of SHR indicated that reducing ET-1,Renin,ANG II and increasing NO,eNOS content are mainly ways for reducing blood pressure.
This paper studied the reducing blood pressure activity of detoxic rapeseed peptides and the mechanism of it in mice.Control group,positive group,detoxic rapeseed peptides group and detoxic rapeseed protein group were set.The rats in each group were gavaged with captopril,detoxic rapeseed peptides and detoxic rapeseed protein in single gavaged test and 30 days gavaged test.The effect of detoxic rapeseed peptides on reducing blood pressure,its effect organs and its mechanism were detected through measuring blood pressure,measuring ACE activity in organs and content of related biochemical index in rats' serum.The maximum decrease quantity are 24.4 mm Hg and 13.3 mm Hg respectively.The results showed that gavaging detoxic rapeseed peptides could significantly reduce SBP in 2-12 h after gavageing(P<0.05),while DBP was only significantly reduced in 4-8 h during the single gavaged test(P<0.05).Detoxic rapeseed peptides can also significantly reduce rats' SBP and DBP in one week during 30 days gavaged test(P<0.05).Effect organs of detoxic rapeseed peptides are lung,kidney and artery in SHR and detoxic rapeseed peptides could decline the activity of ACE in these organs.Indexes content in serum of SHR indicated that reducing ET-1,Renin,ANG II and increasing NO,eNOS content are mainly ways for reducing blood pressure.
引文
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[22]YU W,GAO J,XUE Z,et al.Radical-scavenging activity,ACE-inhibiting capability and identification of rapeseed albumin hydrolysate[J].Food Science&Human Wellness,2013,2(2):93-98.
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[24]孟馥芬,张建龙,马琪.脓毒血症过程中大鼠心功能及心肌酶指标的动态变化[J].新疆医科大学学报,2005,28(2):128-130.
[25]雷安平,陈欢,黎双飞,等.谷胱甘肽S-转移酶的功能、应用及克隆表达[J].环境科学与技术,2009,32(12):85-91.
[2]王文.中国高血压基层管理指南(2014年修订版)[J]中国医学前沿杂志电子版,2015,30(7):18-40.
[3]JULIUS S,KJELDSEN S E,WEBER M,et al Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine:The VALUE randomised trial[J].Lancet,2004,363(9426):2022-2031.
[4]吴兆苏,霍勇,王文,等.中国高血压患者教育指南[J].中华高血压杂志,2013,6(12):78-110.
[5]冯晶晶,王小万,王增武,等.高血压管理的国际经验及启示[J].中国药房,2014,25(18):1711-1714.
[6]MIGUELCARRASCO J L,MONSERRAT M T,MATE A,et al.Comparative effects of captopril and L-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats[J].European Journal of Pharmacology,2010,632(1/2/3):65-72.
[7]FAROOQ A,TOSHEVA L,AZZAWI M,et al Real-time observation of aortic vessel dilation through delivery of sodium nitroprusside via slow release mesoporous nanoparticles[J].Journal of Colloid&Interface Science,2016,478(15):127-135.
[8]滕超.酶解-膜分离耦合制备米糠ACEI肽的研究[D]镇江:江苏大学,2007.
[9]LEO F D,PANARESE S,GALLERANI R,et al Angiotensin converting enzyme(ACE)inhibitory peptides:Production and implementation of functional food[J].Current Pharmaceutical Design,2009,15(31):3622-3643.
[10]任欢.菜籽蛋白ACE抑制肽的制备及分离纯化研究[D].长沙:湖南农业大学,2011.
[11]何荣,鞠兴荣.菜籽蛋白水解物及其膜分离组分的降血压相关活性[J].食品科学,2013,34(15):57-61.
[12]MIGUEL M,ALEIXANDRE A.Antihypertensive peptides derived from egg proteins[J].J Nutr,2006,136(6):1457-1460.
[13]SAITO T,NAKAMURA T,KITAZAWA H,et al Isolation and structural analysis of antihypertensive peptides that exist naturally in Gouda cheese[J].JDairy Sci,2000,83(7):1434-1440.
[14]刘大川,周俊梅,张寒俊,等.低植酸、低单宁“双低”菜籽分离蛋白制备工艺的研究[J].中国油脂,2005,30(8):38-41.
[15]李云亮.金枪鱼降血压肽的基因设计、克隆表达和活性评价[D].无锡:江苏大学,2015.
[16]PORTER A J,PILLIDGE K,GRABOWSKA E M,et al.The angiotensin converting enzyme inhibitor,captopril,prevents the hyperactivity and impulsivity of neurokinin-1 receptor gene‘knockout’mice:Sex differences and implications for the treatment of attention deficit hyperactivity disorder[J].European Neuropsychopharmacology,2015,25(4):512-521.
[17]LI G H,LE G W,SHI Y H,et al.Angiotensin I-converting enzyme inhibitory peptides derived from food proteins and their physiological and pharmacological effects[J].Nutrition Research,2004,24(7):469-486.
[18]唐蕊,李海涛,马文君,等.正常高值血压患者血清内皮素、一氧化氮与炎性因子水平变化及其意义[J].中国循环杂志,2009,24(3):210-212.
[19]陈国阳,张清平,苏松森,等.肿瘤坏死因子拮抗剂对强直性脊柱炎患者血清相关细胞因子变化的影响及其机制研究[J].现代生物医学进展,2014,14(28):5486-5490.
[20]张珂.内皮素受体在人食管下括约肌的表达及调节机制的研究[D].石家庄:河北医科大学,2014.
[21]DEMIRALAY E,SAGLAM I Y,OZDAMAR E N,et al.nNOS expression in the brain of rats after burn and the effect of the ACE inhibitor captopril[J].Burns Journal of the International Society for Burn Injuries,2013,39(5):897-904.
[22]YU W,GAO J,XUE Z,et al.Radical-scavenging activity,ACE-inhibiting capability and identification of rapeseed albumin hydrolysate[J].Food Science&Human Wellness,2013,2(2):93-98.
[23]唐坤裕.大鼠脑缺血后适应的PI3K/Akt-eNOS-NO信号通路的实验研究[D].昆明:昆明医科大学,2013.
[24]孟馥芬,张建龙,马琪.脓毒血症过程中大鼠心功能及心肌酶指标的动态变化[J].新疆医科大学学报,2005,28(2):128-130.
[25]雷安平,陈欢,黎双飞,等.谷胱甘肽S-转移酶的功能、应用及克隆表达[J].环境科学与技术,2009,32(12):85-91.