自发性高血压大鼠血浆代谢组学研究及人参总皂苷作用机制初探

Investigations into Metabonomic Profiling of Spontaneously Hypertensive Rat (SHR) and Metabolic Effects of Total Ginsenoside on SHR Using GC/MS

目的:探讨自发性高血压大鼠(SHR)和正常大鼠(WKY)血浆代谢组差异,确证高血压模型,在此基础上探讨人参总皂苷对SHR血压及代谢组的影响。方法:15只12周龄的雄性SHR和15只同龄WKY大鼠经2周适应性饲养后测量大鼠尾动脉收缩压(SBP)、舒张压(DBP),同时收集血浆应用GC/MS测定内源性代谢物,用主成分分析(PCA)和偏最小二乘方判别分析(PLS-DA)分析两组动物的代谢谱及引起高血压的生物标记物。将SHR随机分成3组,人参总皂苷组:100mg.kg.d-1;卡托普利组:100mg.kg.d-1;SHR模型组:等量0.5%CMC-Na及WKY组等量0.5%CMC-Na,连续灌胃4周,SHR模型组和人参总皂苷组继续给药至8周后,测量大鼠尾动脉SBP、DBP及血浆内源性代谢物。结果:与WKY组相比,SHR组的SBP、DBP及血浆代谢组均有显著差异,SHR组内源性代谢物中十六酸、吡喃半乳糖、十八碳二烯酸、羟基丁酸等化合物的浓度显著增高。给药后,卡托普利组能显著降低SBP(P<0.01)和SBP(P<0.01);尽管人参总皂苷组对血压的作用不如卡托普利组明显,但前者的代谢谱较后者向正常组代谢谱靠近的趋势更加明显。结论:SHR组和WKY组血浆代谢组有显著差异,这将为进一步探讨高血压病相关的致病基因提供物质基础。长期应用人参治疗,能改善血浆代谢组,使机体的功能趋于正常。

AIM： To investigate the metabolic profiling of SHR and fifteen WKY as well as metabolic effects of total ginsenoside （TG） on SHR using GC/MS. METHODS： Fifteen male SHR and WKY aged 12 weeks were housed to fit the new environment for 2 weeks. After that, blood pressures were measured using a tail-cuff method just before plasma collection. Metabolic profiles for SHR and WKY were acquired using GC/MS. Principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） were applied to these complex GC/MS data to facilitate differentiation and determine metabolic differences between plasma samples collected from hypertensive and normotensive rats. Consequently, 15 SHR were randomly divided into 3 groups with 5 SHR each, which were treated with TG, 0.5 % CMC, for 8 weeks and with Captopril （CAP） （ 100 mg· kg· d^-1 ） for 4 weeks. Then blood pressures were measured and metabolic profiles were acquired using GC/MS. RESULTS：The Systolic blood pressure （SBP） and Diastolic blood pressure （DBP） of SHR were significantly higher than those of WKY. Using PCA and PLS-DA, it is also possible to distinguish them in the principal components score plot. In SHR, the plasma levels of hexadecanoic acid, galactapyranoside, octadecadienoic acid and butanoic acid were found to be higher. Compared with control SHR, the SBP and DBP were significantly reduced in CAP treated SHR （ P 〈 0.01 ）, and slightly reduced in TG treated SHR. But the metabolic profiles of SHR treated with TG were becoming normal. CONCLUSION： GC/MS is a promising approach to provide the information on metabolic changes related to the pathophysiological processes of the spontaneously hypertensive rats. Treated with TG for a long period, the pathophysiological processes of SHRs could be partially improved.