莱菔子水溶性生物碱对自发性高血压大鼠降压和早期肾保护作用的实验研究
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摘要
目的：本文在中医理论指导下，结合现代研究，观察探讨莱菔子水溶性生物碱降压作用及保护自发性高血压大鼠(SHR)早期肾损害的机理。方法：将40只SHR随机分为5组：空白对照组、莱菔子水溶性生物碱高、中、低剂量组、卡托普利组，每组8只。采用尾动脉测压法每两周测一次血压，于给药8周后，摘取肾脏，制作肾组织石蜡切片，HE染色，光镜下观察大鼠肾小动脉的变化，并测量每张切片肾小动脉壁厚／腔径的比值，取均值。结果：给药8周后，莱菔子水溶性生物碱明显降低了SHR的血压，其中高、中剂量组的降压幅度与卡托普利组比较无显著性差异，同时莱菔子各组和卡托普利组均使SHR的肾动脉得到了一定程度的改善。结论：高血压早期肾损害主要发病机制为肝阳上亢，痰浊阻肾。因此立“降气化痰，通腑泻浊”作为主要治法。研究证实莱菔子水溶性生物碱具有明显的降压作用，同时对高血压引起的早期肾损害具有保护作用。
Objective:under the direction of traditional Chinese medicine(TCM),combining modern research,to observe and discuss the mechanism of raphani soluble alkaloid on depressurization and protection for early-stage kidney damage of spontaneous hypertensive rat(SHR).Method : 40 SHR were randomly divided into 5 groups: control group, raphani soluble alkaloid groups with high,middle or low dosage respectively, captopril group. correspondingly 8 SHR for each group. blood pressure was tested every two weeks by caudal artery manometry, 8weeks after administration, animals were fasted for 12 hours,then their abdomens were opened, furthermore they were put to death by haemospasia and their kidney artery were cut and put into fixative solution containing 10% formaldehyde .24 hours after fixation, wax section and HE dying were prepared for observing the change of kidney arteriole under light microscope, at the same time , the ratio of thickness to cavity diameter for each section was measured and mean value was calculated. Result: 8weeks after administration, raphani soluble alkaloid could lower the blood pressure of SHE obviously, among which high and middle dosage groups manifested no significant difference from captopril group, while each group of raphani soluble alkaloid showed improvement on kidney arteriole of SHE to some extent .Conclusion : the main mechanism of early-stage kidney damage along with hypertension is hyperactivity of liver-YANG, muddy sputum hindering kidney. So "lowering adverse-rising energy and dissipating phlegm, FU-organ smoothness and turbidity evacuation" should be applied as major treatment method .research has proved that raphani soluble alkaloid has conspicuous depressurization and give protection role to early-stage kidney damage aroused by hypertension.
Objective:under the direction of traditional Chinese medicine(TCM),combining modern research,to observe and discuss the mechanism of raphani soluble alkaloid on depressurization and protection for early-stage kidney damage of spontaneous hypertensive rat(SHR).Method : 40 SHR were randomly divided into 5 groups: control group, raphani soluble alkaloid groups with high,middle or low dosage respectively, captopril group. correspondingly 8 SHR for each group. blood pressure was tested every two weeks by caudal artery manometry, 8weeks after administration, animals were fasted for 12 hours,then their abdomens were opened, furthermore they were put to death by haemospasia and their kidney artery were cut and put into fixative solution containing 10% formaldehyde .24 hours after fixation, wax section and HE dying were prepared for observing the change of kidney arteriole under light microscope, at the same time , the ratio of thickness to cavity diameter for each section was measured and mean value was calculated. Result: 8weeks after administration, raphani soluble alkaloid could lower the blood pressure of SHE obviously, among which high and middle dosage groups manifested no significant difference from captopril group, while each group of raphani soluble alkaloid showed improvement on kidney arteriole of SHE to some extent .Conclusion : the main mechanism of early-stage kidney damage along with hypertension is hyperactivity of liver-YANG, muddy sputum hindering kidney. So "lowering adverse-rising energy and dissipating phlegm, FU-organ smoothness and turbidity evacuation" should be applied as major treatment method .research has proved that raphani soluble alkaloid has conspicuous depressurization and give protection role to early-stage kidney damage aroused by hypertension.
引文
[1] 程广书．高血压肾损害的中医药治疗思路．河南中医，2001；21(1)：31．
[2] 严冬，蒋卫民，唐蜀华．降压益肾颗粒治疗高血压病早期肾损害35例疗效观察．中医药研究[J]．1999；15(1)6-7．
[3] 唐树德，王崇行，刘国明．首乌治疗早期肾脏损害血癖型高血压患者28例．中国中西医结合杂志，1994；14 (5)：302-303．
[4] 王清海，卢桂梅，李爱华，等．血压健胶囊治疗气虚痰浊型高血压的临床研究．新中医，1998；30(1)：35-36．
[5] 吴云霞，李云善，张国欣，等．早期肾损害的检测及氨杞精口服液对其疗效观察．中国中医药科技，1998；5(2)：115-116．
[6] 张琪，朱建军．观察保元灌肠液治疗原发性高血压患者早期肾损害的疗效60例．南京中医药大学学报[J]．自然科学版2001；17(3)：189-190．
[7] 陈政光．固本降压合剂治疗中老年高血压临床研究．山东中医杂志，2002；21(2)：72-73．
[8] 方企扬等．补肾活血方治疗高血压病80例．江苏中医[J]．1998；19(11)：22-23．
[9] 朱遵贤．利水解毒法治疗高血压肾病52例．陕西中医[J]．1999；20(8)：345．
[10] 周建忠等．灯盏细辛注射液对自发高血压大鼠心室及血管重构的影响冲国中西医结合杂志[J]．2002；22(2)：122．
[11] 吴伟，刘煜德．补肾益心片对肾血管性高血压大鼠的降压作用及保护靶器官的研究．广州中医药大学学报[J]．2001；18(1)：63-66．
[12] 严冬等．降压益肾颗粒对SHR循环系统及组织中NO、NOS的影响．江苏中医[J]．2001；22(6)：40-42．
[13] 袁成民等．八物降压冲剂治疗原发性高血压．山东中医药大学学报[J]．1999；23(3)：189-193．
[14] 唐树德等．首乌治疗早期肾脏损害血瘀型高血压患者28例．中国中西医结合杂志[J]．1994；5：302-303．
[15] 张琪，朱建军．观察保元灌肠液治疗原发性高血压(EH)患者早期肾损害的疗效南京中医药大学学报[J]．自然科学版2001；17(3)：189-190．
[16] 赵光胜．现代高血压学．北京：人民军医出版社，1999；第一版：340-341．[17]Pomsh JG.Hypertension and chronic renal failure:the use of ACEinhibitors. Am J Kidney Dis, 1998;31:177.
[18] 林善琐．肾脏与高血压．临床心血管杂志，1996；12(9)：39．
[19] MogeusenCE,DasoprdEM.FrolandAetal.Microalbuminuria .InNoninsulin-dependent Diabetes. Clin Nephrol, 1992;38(Suppl): 28.
[20] 陆菊明．02-MG的临床意义．国外医学《内科学分册》，1984；10：4752．
[21] 刘力兰，龚兰生，孔华宁主编．临床高血压病学．天津：科学技术出版社，1990；第1版，112-113．
[22] Helsuchen U Effects of Hypertension on Renal Vasculature and Structure.In: Cameron S, Davlson AM. Oxford Textbook of Clinical Nephrology .Vol. 1st ed.Oxford: Oxford University Press: 1992;2075.
[23] Sommers SC, Mclaughlin RJ. Patblogy of diastolic hypertension as ageneralized vascutar disease. Am J Cardiol, 1962;9: 653.
[24] Hollenberg NK, Adams DF. Renal vascular tone in essemlaland secondavhypertenson.Medicine, 1975;54: 29.
[25] Fogo AB.Glomerular hypertension,abnormal glomerular growth, and progesssio of renal diseases [J]. Kidney Int Suppl,2000;75:s15.
[26] Salvetti A,Mattei P,Sudano I.Renal protection and antihypertensive drug [J]. Drug, 1999;57(5):665.
[27] Peters H,Border WA,Noble NA.Targeting TGF-beta overexpression in renal disease:maximizing the antifibroticaction of angiotensin blockade[J]. Kidney Int,1998; 54(5):1570.
[28] Klahr S Morrissey JJ. The role of vasoactive compounds,growthfactors ang cytokines in the progression of renal disease [J]. Kidney Int,2000;57(175):s7.
[29] Griffin KA,P icken MM,Bidani AK.Class difference in the effects of calcium channel blockade in the remnant kidney model[J]. Kidney llint, 1999;55:1849
[30] Cain AE,khalil R Pathophysiology of essential hypertension:Role of the pump,the vessel and the kidney [J].Seminars in Nephrology,2003;22(1):3
[31] Churchill PC,Churchill MC,Bidanr AK, etal.Genetic susceptibisity to hypertension in duced renal damage in the mt. Evrdence based on kidney specific genome transfer[J]. JClin in vest, 1977; 100(6):1373.
[32] Maschio G,Alberti D,Janin G,Et ai. Effect of Angiotensin-converting engyme inbibitor benagepril on the progression of chronic ienalinsufficiency [J]. N Eng J Med,1996;334:939.
[33] Giatrras I,Laeo J,Levey AS,etal.Effect of angiotensin-converting-engyme inhiditor I on the progression of non-diabeticrenal disease:a meta-analysis of randomized trials[J].Ann Intern Med, 1997; 127:337.
[34] Ruggenenti P,Pema A,Gherardi G,etal.Renoprotective properties of ACE-inhibition in non-diabetic nephropathies withnon-aephrotic proteinuria[J].Lancet, 1999;3 54:359.
[35] Agodoa LY,Appel L,Bakris GL,Etal.Effect of ramipril vs amlodipiae on renal outcomes in hypertensive nephrosclerosis[J]. JAMA,2001 ;285(21):2719.
[36] Giffin KA,Picken M,Bidanr ak,etal. Deleterious effects of calcium channel blockade on pressure transmission and glomerular in jury in rat remmant kidneys [J].J Clin Invest, 1995 ;96:793.
[37] Wright JT Jr, Bakris G,Greene T,Etal.Effect of blood pressure lowering and antihvpertensive drug class on progression of hypertensive kidney disease:results from theAASK trial[J]. JA-MA,2002;288(19):2421.
[38] 王维兰，朱进，李钟大等．莱菔子降压活性成分的研究．中草药，1987；18(8)：5．
[39] 张永和，等．莱菔子注射液降压作用的实验研究．吉林中医药，1996；(5)：41．
[40] 施波，宋爱英，隋明，等．莱菔子对家兔急性缺氧性肺动脉高压的降压作用研究．中草药，1990；21(10)：25-27．
[41] 于晓风，睢大员，曲绍春．莱葛冲剂对自发性高血压大鼠的降压作用研究．人参研究2000；12(4)：19．
[42] 莱萌．治疗高血压病性新药—莱菔子降压片的研究．医学研究通讯，1986；15(6)：185-186．
[43] 宋爱英，等．莱菔子对麻醉犬心脏血流动力学的作用研究．中医药学报1990；(1)：48．
[44] 睢大员．莱葛冲剂对麻醉开胸犬血流动力学的影响．中草药，1996；27(4)：220．
[45] 刘继增．莱菔子治疗高血压疗效观察．中西医结合杂志，1986；6(2)：110．
[46] 马群，马健．莱菔子降血压效佳[J]．中医杂志，1998；39(8)：454．
[47] 翟瑞庆，崔迎春．莱菔子善治高血压[J]．中医杂志，1998；39(8)：454．
[48] 罗伟，苏海，程小曙等．尼群地平与卡托普利对高血压靶器官结构及功能损害的影响．江西医学院学报．1999；40(3)：107．
[2] 严冬，蒋卫民，唐蜀华．降压益肾颗粒治疗高血压病早期肾损害35例疗效观察．中医药研究[J]．1999；15(1)6-7．
[3] 唐树德，王崇行，刘国明．首乌治疗早期肾脏损害血癖型高血压患者28例．中国中西医结合杂志，1994；14 (5)：302-303．
[4] 王清海，卢桂梅，李爱华，等．血压健胶囊治疗气虚痰浊型高血压的临床研究．新中医，1998；30(1)：35-36．
[5] 吴云霞，李云善，张国欣，等．早期肾损害的检测及氨杞精口服液对其疗效观察．中国中医药科技，1998；5(2)：115-116．
[6] 张琪，朱建军．观察保元灌肠液治疗原发性高血压患者早期肾损害的疗效60例．南京中医药大学学报[J]．自然科学版2001；17(3)：189-190．
[7] 陈政光．固本降压合剂治疗中老年高血压临床研究．山东中医杂志，2002；21(2)：72-73．
[8] 方企扬等．补肾活血方治疗高血压病80例．江苏中医[J]．1998；19(11)：22-23．
[9] 朱遵贤．利水解毒法治疗高血压肾病52例．陕西中医[J]．1999；20(8)：345．
[10] 周建忠等．灯盏细辛注射液对自发高血压大鼠心室及血管重构的影响冲国中西医结合杂志[J]．2002；22(2)：122．
[11] 吴伟，刘煜德．补肾益心片对肾血管性高血压大鼠的降压作用及保护靶器官的研究．广州中医药大学学报[J]．2001；18(1)：63-66．
[12] 严冬等．降压益肾颗粒对SHR循环系统及组织中NO、NOS的影响．江苏中医[J]．2001；22(6)：40-42．
[13] 袁成民等．八物降压冲剂治疗原发性高血压．山东中医药大学学报[J]．1999；23(3)：189-193．
[14] 唐树德等．首乌治疗早期肾脏损害血瘀型高血压患者28例．中国中西医结合杂志[J]．1994；5：302-303．
[15] 张琪，朱建军．观察保元灌肠液治疗原发性高血压(EH)患者早期肾损害的疗效南京中医药大学学报[J]．自然科学版2001；17(3)：189-190．
[16] 赵光胜．现代高血压学．北京：人民军医出版社，1999；第一版：340-341．[17]Pomsh JG.Hypertension and chronic renal failure:the use of ACEinhibitors. Am J Kidney Dis, 1998;31:177.
[18] 林善琐．肾脏与高血压．临床心血管杂志，1996；12(9)：39．
[19] MogeusenCE,DasoprdEM.FrolandAetal.Microalbuminuria .InNoninsulin-dependent Diabetes. Clin Nephrol, 1992;38(Suppl): 28.
[20] 陆菊明．02-MG的临床意义．国外医学《内科学分册》，1984；10：4752．
[21] 刘力兰，龚兰生，孔华宁主编．临床高血压病学．天津：科学技术出版社，1990；第1版，112-113．
[22] Helsuchen U Effects of Hypertension on Renal Vasculature and Structure.In: Cameron S, Davlson AM. Oxford Textbook of Clinical Nephrology .Vol. 1st ed.Oxford: Oxford University Press: 1992;2075.
[23] Sommers SC, Mclaughlin RJ. Patblogy of diastolic hypertension as ageneralized vascutar disease. Am J Cardiol, 1962;9: 653.
[24] Hollenberg NK, Adams DF. Renal vascular tone in essemlaland secondavhypertenson.Medicine, 1975;54: 29.
[25] Fogo AB.Glomerular hypertension,abnormal glomerular growth, and progesssio of renal diseases [J]. Kidney Int Suppl,2000;75:s15.
[26] Salvetti A,Mattei P,Sudano I.Renal protection and antihypertensive drug [J]. Drug, 1999;57(5):665.
[27] Peters H,Border WA,Noble NA.Targeting TGF-beta overexpression in renal disease:maximizing the antifibroticaction of angiotensin blockade[J]. Kidney Int,1998; 54(5):1570.
[28] Klahr S Morrissey JJ. The role of vasoactive compounds,growthfactors ang cytokines in the progression of renal disease [J]. Kidney Int,2000;57(175):s7.
[29] Griffin KA,P icken MM,Bidani AK.Class difference in the effects of calcium channel blockade in the remnant kidney model[J]. Kidney llint, 1999;55:1849
[30] Cain AE,khalil R Pathophysiology of essential hypertension:Role of the pump,the vessel and the kidney [J].Seminars in Nephrology,2003;22(1):3
[31] Churchill PC,Churchill MC,Bidanr AK, etal.Genetic susceptibisity to hypertension in duced renal damage in the mt. Evrdence based on kidney specific genome transfer[J]. JClin in vest, 1977; 100(6):1373.
[32] Maschio G,Alberti D,Janin G,Et ai. Effect of Angiotensin-converting engyme inbibitor benagepril on the progression of chronic ienalinsufficiency [J]. N Eng J Med,1996;334:939.
[33] Giatrras I,Laeo J,Levey AS,etal.Effect of angiotensin-converting-engyme inhiditor I on the progression of non-diabeticrenal disease:a meta-analysis of randomized trials[J].Ann Intern Med, 1997; 127:337.
[34] Ruggenenti P,Pema A,Gherardi G,etal.Renoprotective properties of ACE-inhibition in non-diabetic nephropathies withnon-aephrotic proteinuria[J].Lancet, 1999;3 54:359.
[35] Agodoa LY,Appel L,Bakris GL,Etal.Effect of ramipril vs amlodipiae on renal outcomes in hypertensive nephrosclerosis[J]. JAMA,2001 ;285(21):2719.
[36] Giffin KA,Picken M,Bidanr ak,etal. Deleterious effects of calcium channel blockade on pressure transmission and glomerular in jury in rat remmant kidneys [J].J Clin Invest, 1995 ;96:793.
[37] Wright JT Jr, Bakris G,Greene T,Etal.Effect of blood pressure lowering and antihvpertensive drug class on progression of hypertensive kidney disease:results from theAASK trial[J]. JA-MA,2002;288(19):2421.
[38] 王维兰，朱进，李钟大等．莱菔子降压活性成分的研究．中草药，1987；18(8)：5．
[39] 张永和，等．莱菔子注射液降压作用的实验研究．吉林中医药，1996；(5)：41．
[40] 施波，宋爱英，隋明，等．莱菔子对家兔急性缺氧性肺动脉高压的降压作用研究．中草药，1990；21(10)：25-27．
[41] 于晓风，睢大员，曲绍春．莱葛冲剂对自发性高血压大鼠的降压作用研究．人参研究2000；12(4)：19．
[42] 莱萌．治疗高血压病性新药—莱菔子降压片的研究．医学研究通讯，1986；15(6)：185-186．
[43] 宋爱英，等．莱菔子对麻醉犬心脏血流动力学的作用研究．中医药学报1990；(1)：48．
[44] 睢大员．莱葛冲剂对麻醉开胸犬血流动力学的影响．中草药，1996；27(4)：220．
[45] 刘继增．莱菔子治疗高血压疗效观察．中西医结合杂志，1986；6(2)：110．
[46] 马群，马健．莱菔子降血压效佳[J]．中医杂志，1998；39(8)：454．
[47] 翟瑞庆，崔迎春．莱菔子善治高血压[J]．中医杂志，1998；39(8)：454．
[48] 罗伟，苏海，程小曙等．尼群地平与卡托普利对高血压靶器官结构及功能损害的影响．江西医学院学报．1999；40(3)：107．