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杜仲抗高血压有效部位的制备及降压效应研究

Preparation of Antihypertensive Effective Fractions of Eucommia Ulmoides Oliv. and Its Hypotensive Effect Study

【作者】 吴卫华

【导师】 欧阳冬生;

【作者基本信息】 中南大学 , 药理学, 2007, 硕士

【摘要】 目的:从杜仲中制备木脂素和环烯醚萜两个部位,分别考察二者的降压效应和协同作用,以确定杜仲降压的主要部位。方法:采用醇提,大孔树脂吸附,水、醇洗脱的方法富集杜仲中的木脂素类和环烯醚萜类成分,并利用Sephadex LH-20、RPC-C18分离纯化松脂醇二糖苷(PDG)单体。用UV、HPLC的方法分别测定有效部位及单体成分含量。将不同剂量的杜仲木脂素部位、杜仲环烯醚萜部位以及两者合并后的提取物通过静脉注射及灌胃的方式考察他们的对正常SD大鼠及SHR大鼠血压的影响。通过颈动脉直接测量静脉注射时正常SD大鼠血压的变化,通过尾动脉测量灌胃给药后SHR大鼠血压的变化。结果:分离得到的PDG单体纯度达到98.8%。制备的杜仲木脂素有效部位木脂素的含量为71%,杜仲环烯醚萜有效部位环烯醚萜含量为60%,均达到中药5类新药标准。静脉给药实验表明:不同剂量杜仲木脂素(30,60 mg·kg-1)对SD大鼠血压具有下降作用(与阴性对照组比较,P<0.05),且不同剂量之间也存在显著性差异(P<0.05),30,60 mg·kg-1杜仲木脂素的最大降压幅分别为37±9、57±4 mmHg,两者存在显著性差异(P<0.05);杜仲环烯醚萜(15~60 mg·kg-1)对SD大鼠血压的影响与阴性对照组无差别(P>0.05);杜仲木脂素与环烯醚萜合用与单用杜仲木脂素的降压效果无差别(P>0.05)。灌胃给药实验表明:不同剂量杜仲木脂素(150,300 mg·kg-1·d-1)可使SHR大鼠血压下降(与阴性对照组比较,P<0.05),一天给药两次能产生较好的降压效果,给药后第4天可产生稳定的降压作用,150、300 mg·kg-1·d-1杜仲木脂素产生的最大降压效应分别为15±6、36±9 mmHg,两者存在显著性差异(P<0.05);杜仲环烯醚萜(125mg·kg-1·d-1)对SHR大鼠血压无影响(P>0.05);杜仲木脂素与环烯醚萜合用与单用杜仲木脂素的降压效果无差别(P>0.05)。结论:我们制备的杜仲木脂素和环烯醚萜两个有效部位,含量分别为71%和60%,达到中药5类新药标准;杜仲木脂素具有剂量依赖性降压作用,杜仲环烯醚萜无降压作用,两者合用无协同作用,杜仲木脂素是杜仲的主要降压部位。

【Abstract】 Aim: To prepare lignans fraction and iridoids fraction from Eucommiaulmoides Oliv., and to evaluate their hypotensive effect single and together, tofind out the main fractions for antihypertension.Method: Using ethanol extracting, macroporous resin sticking, water orethanol eluotropic method to enrich lignans and iridoids components inEucommia ulmoides Oliv. To isolate pinoresinol glucoside (PDG) monomer bySephadex LH-20, RPC-C18. To determine the content of effective fractionand monomer using UV and HPLC method. To investigate their hypotensiveeffect on norrnotensive SD rats and SHRs after they were administrated byintravenous injection or intragastfic gavage. Blood pressure was measureddirectly in carotid artery or by the tail-cuff method.Results: The purity of PDG monomer we isolated was 98.8%. Thecontent of the lignans and the iridoids prepared from Eucomrnia ulmoides Oliv.were 70%and 60%respectively, reach the standard of Chinese traditionalnew medicine type 5. Our pharmacodynamic experiment show thatintravenous administration of 30, 60 mg·kg-1Eucommia ulrnoides Oliv. lignansdecreased SD rats blood pressure dose-dependently (P<0.05), the maximaleffects produced by 30, 60 mg/kg were 37±9, 57±4 mmHg respectively andthere were significant difference between them (P<0.05) ; but there is noeffect with 15~60 mg·kg-1Eucommia ulmoides Oliv. iridoids. The hypotensiveeffect produced by the lignans and the iridoids together have no significantdifference with the single lignans (P>0.05). Oral administration of 150, 300mg·kg-1·d-1Eucommia ulmoides Oliv. lignans also decreased SHRs bloodpressure dose-dependently (P<0.05). The regimen of twice a day has agood hypotensive effect and a steady effect was reached at d 4 afteradministration. The maximal effects produced by 150, 300 mg·kg-1·d-1were 15±6、36±9 mmHg respectively and there were significant difference betweenthem (P<0.05); and there is no effect with 125 mg·kg-1·d-1 Eucommiaulmoides Oliv. iridoids; and the hypotensive effect produced by the lignansand the iridoids together have no significant difference with the single lignans(P>0.05) Conclusion: The content of the lignans and the iridoids prepared fromEucommia ulmoides Oliv. were 70%and 60%respectively, reach the standardof Chinese traditional new medicine type 5. Eucommia ulmoides Oliv. lignanshave dose-dependently hypotensive effect. Eucommia ulmoides Oliv. iridoidshave no hypotensive effect. The combination of them produces no synergisticeffect. Eucommia ulmoides Oliv. lignans is the main effective fractions forantihypertension.

  • 【网络出版投稿人】 中南大学
  • 【网络出版年期】2007年 06期
  • 【分类号】TQ461;R285
  • 【被引频次】15
  • 【下载频次】812
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