高血压大鼠模型的建立及抗高血压药效评价指标体系研究
|
摘要
高血压是一种以动脉血压升高为特征的疾病。建立高血压动物模型及抗高血压药效评价指标体系有助于高血压预防和治疗研究。
本研究通过每天给大鼠灌喂定量的一氧化氮合酶抑制剂N~G-Nitro-L-arginine Methyl Ester(L-NAME)建立了高血压模型，通过应用生理参数遥测系统记录和分析高血压形成及抗高血压治疗中血压、心电等生理信号，建立了一套血压评价指标体系，并首次提出了评价血压下降平稳程度的新指标——每小时平滑指数和24h平滑指数趋势图。
本研究建立的高血压大鼠模型，方法简单、对动物的人为影响小、稳定且复制率高。血压评价指标体系不仅从血压负荷、昼夜节律等各个方面而且从每小时、白昼、夜间、全天等各个时段评价了抗高血压药物的疗效。每小时平滑指数和24h平滑指数趋势图克服了谷峰比时常与实际情况不符及全天平滑指数反映药物降压情况太笼统的缺点，更准确、具体地评价了抗高血压药物的疗效。
本研究建立的高血压大鼠模型及抗高血压药效评价血压指标体系，为评价及筛选抗高血压药物提供了有效工具。
Hypertension is a disease whose character is high arterial blood pressure. Hypetensive animal models and Hypetensive medication evaluating indexes redound to hypertensive treating and preventing study.
Quantificational NG-Nitro-L-arginine Methyl Ester (L-NAME) was oral administrated daily in Sprague-Dawley rats to come into being hypertension. Ambulatory blood pressure, ECG etc physiologic signals were collected and recorded by telemetry physiologic system, based which blood pressure evaluating indexes system was set up. The new indexes to estimating blood pressure descending degree, smoothness index of each hour and 24h smoothness index chart, were firstly brought forward by this study.
The model made by this study is a good hypertensive animal model with simple and convenient manipulation, stable hypertension, high replication ratio and little factitious influence. Hypertensive medicaments were evaluated not only from blood pressure load, day and night rhythm etc diverse angles but also from each hour, daytime, nighttime, the whole day etc diverse periods by the series of blood pressure indexes. Smoothness index of each hour and 24h smoothness index chart could overcome those shortcomings that trough-to-peak ratio was opposite to actual results sometimes and smoothness index of the whole day reflected the blood pressure descending state cursorily and appraise medication more exactly and more concretely.
The hypertensive animal model and the antihypetensive medication evaluating indexes system made by this study offer effective tools for appraising and filtrating antihypetensive medication.
本研究通过每天给大鼠灌喂定量的一氧化氮合酶抑制剂N~G-Nitro-L-arginine Methyl Ester(L-NAME)建立了高血压模型，通过应用生理参数遥测系统记录和分析高血压形成及抗高血压治疗中血压、心电等生理信号，建立了一套血压评价指标体系，并首次提出了评价血压下降平稳程度的新指标——每小时平滑指数和24h平滑指数趋势图。
本研究建立的高血压大鼠模型，方法简单、对动物的人为影响小、稳定且复制率高。血压评价指标体系不仅从血压负荷、昼夜节律等各个方面而且从每小时、白昼、夜间、全天等各个时段评价了抗高血压药物的疗效。每小时平滑指数和24h平滑指数趋势图克服了谷峰比时常与实际情况不符及全天平滑指数反映药物降压情况太笼统的缺点，更准确、具体地评价了抗高血压药物的疗效。
本研究建立的高血压大鼠模型及抗高血压药效评价血压指标体系，为评价及筛选抗高血压药物提供了有效工具。
Hypertension is a disease whose character is high arterial blood pressure. Hypetensive animal models and Hypetensive medication evaluating indexes redound to hypertensive treating and preventing study.
Quantificational NG-Nitro-L-arginine Methyl Ester (L-NAME) was oral administrated daily in Sprague-Dawley rats to come into being hypertension. Ambulatory blood pressure, ECG etc physiologic signals were collected and recorded by telemetry physiologic system, based which blood pressure evaluating indexes system was set up. The new indexes to estimating blood pressure descending degree, smoothness index of each hour and 24h smoothness index chart, were firstly brought forward by this study.
The model made by this study is a good hypertensive animal model with simple and convenient manipulation, stable hypertension, high replication ratio and little factitious influence. Hypertensive medicaments were evaluated not only from blood pressure load, day and night rhythm etc diverse angles but also from each hour, daytime, nighttime, the whole day etc diverse periods by the series of blood pressure indexes. Smoothness index of each hour and 24h smoothness index chart could overcome those shortcomings that trough-to-peak ratio was opposite to actual results sometimes and smoothness index of the whole day reflected the blood pressure descending state cursorily and appraise medication more exactly and more concretely.
The hypertensive animal model and the antihypetensive medication evaluating indexes system made by this study offer effective tools for appraising and filtrating antihypetensive medication.
引文
1 Guidelines Subcommittee. 1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. J Hypertension, 1999. 17: 151～183
2 全国血压抽样调查协作组．中国人群高血压患病率及其变化趋势．高血压杂志．1995，3(Suppl)：7～13
3 Lowenstein CJ, Solomon HS. Nitric oxide: a novel biologic messenger. Cell, 1992, 70: 705～707
4 Dananberg J, Richard S. Sustained hypertension induced by orally administered Nitro-L-arginine. Hypertension, 1993, 21: 356～363
5 Moncada S, Palmer RMJ, Higgs EA et al. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev, 1991, 43: 109～110
6 Dzau VJ, Gibbons GH. Vascular remodeling: mechanisms and implication. J Cardiovasc Pharmacol, 1993, 21 (Suppl): S1～S6
7 Grimes PA, Mokashi A, Stone RA et al. Nitric oxide synthase in autonomic innervation of the cat carotid body. J Auton Nerv Syst, 1995, 54: 80～86
8 Jimbo M, Suzuk H, Tchilawa M et al. Role of nitric oxide in regulation of baroreceptor reflex. J Auton Nerv Syst, 1994, 50: 209～212
9 Lowenstein CJ, Dinerman JL, Snyder SH. Nitric oxide: a physiologic messenger. Ann Inter Med, 1994, 120: 227～237
10 Rossi MA, Ramos SG, Prado CM. Chronic inhibition of nitric oxide synthase induces hypertension and cardiomyocyte mitochondrial and myocardial collagen remodelling in the absence of hypertrophy. J Hypertens, 2003, 21: 993～1001
11 张维忠．美国和欧洲高血压治疗新指南评析。中华心血管病杂志，2003，31：650～652
12 张维忠，施海明，王瑞冬等．动态血压参数正常参照值协作研究。中华心血管病杂志，1995，10(23)：325～328
13 张维忠，施海明，王瑞冬等．动态血压参数正常参照值协作研究．中华心血
管病杂志，1995，10(23)：325～328
14 Zanchtti PK, Sumner WE. The clinical utility of blood pressure load in hypertension. Am J Hypertens, 1993, 6(6Pt2): 194S
15 黄泰康．常用中药成分与药理手册．北京：中国医药科技出版社。1994，328～352
16 刘昭前，周宏．一氧化氮合酶抑制剂的研究进展．中国药理学通报，1999，15(1)：11～13
17 Pedraza-Chaverri J, Tapia E, Medina-Campos ON et al. Garlic prevents hypertension induced by chronic inhibition of nitric oxide synthesis. Life Sci. 1998, 62(6): PL 71～77
18 Das I, Hirani J, Sooranna S. Arginine is not responsible for the activation of nitric oxide synthase by garlic. J Ethnopharmacol. 1996, 53(1): 5～9
19 Morihara N, Sumioka I, Moriguchi T et al. Aged garlic extract enhances production of nitric oxide. Life Sci. 2002, 71(5): 509～517
20 Qidwai W, Qureshi R, Hasan SN et at. Effect of dietary garlic (Allium Sativum) on the blood pressure in humans-apilot study [J]. J Pak Med Assoc, 2000, 50 (6): 204～207
2 全国血压抽样调查协作组．中国人群高血压患病率及其变化趋势．高血压杂志．1995，3(Suppl)：7～13
3 Lowenstein CJ, Solomon HS. Nitric oxide: a novel biologic messenger. Cell, 1992, 70: 705～707
4 Dananberg J, Richard S. Sustained hypertension induced by orally administered Nitro-L-arginine. Hypertension, 1993, 21: 356～363
5 Moncada S, Palmer RMJ, Higgs EA et al. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev, 1991, 43: 109～110
6 Dzau VJ, Gibbons GH. Vascular remodeling: mechanisms and implication. J Cardiovasc Pharmacol, 1993, 21 (Suppl): S1～S6
7 Grimes PA, Mokashi A, Stone RA et al. Nitric oxide synthase in autonomic innervation of the cat carotid body. J Auton Nerv Syst, 1995, 54: 80～86
8 Jimbo M, Suzuk H, Tchilawa M et al. Role of nitric oxide in regulation of baroreceptor reflex. J Auton Nerv Syst, 1994, 50: 209～212
9 Lowenstein CJ, Dinerman JL, Snyder SH. Nitric oxide: a physiologic messenger. Ann Inter Med, 1994, 120: 227～237
10 Rossi MA, Ramos SG, Prado CM. Chronic inhibition of nitric oxide synthase induces hypertension and cardiomyocyte mitochondrial and myocardial collagen remodelling in the absence of hypertrophy. J Hypertens, 2003, 21: 993～1001
11 张维忠．美国和欧洲高血压治疗新指南评析。中华心血管病杂志，2003，31：650～652
12 张维忠，施海明，王瑞冬等．动态血压参数正常参照值协作研究。中华心血管病杂志，1995，10(23)：325～328
13 张维忠，施海明，王瑞冬等．动态血压参数正常参照值协作研究．中华心血
管病杂志，1995，10(23)：325～328
14 Zanchtti PK, Sumner WE. The clinical utility of blood pressure load in hypertension. Am J Hypertens, 1993, 6(6Pt2): 194S
15 黄泰康．常用中药成分与药理手册．北京：中国医药科技出版社。1994，328～352
16 刘昭前，周宏．一氧化氮合酶抑制剂的研究进展．中国药理学通报，1999，15(1)：11～13
17 Pedraza-Chaverri J, Tapia E, Medina-Campos ON et al. Garlic prevents hypertension induced by chronic inhibition of nitric oxide synthesis. Life Sci. 1998, 62(6): PL 71～77
18 Das I, Hirani J, Sooranna S. Arginine is not responsible for the activation of nitric oxide synthase by garlic. J Ethnopharmacol. 1996, 53(1): 5～9
19 Morihara N, Sumioka I, Moriguchi T et al. Aged garlic extract enhances production of nitric oxide. Life Sci. 2002, 71(5): 509～517
20 Qidwai W, Qureshi R, Hasan SN et at. Effect of dietary garlic (Allium Sativum) on the blood pressure in humans-apilot study [J]. J Pak Med Assoc, 2000, 50 (6): 204～207