甘肃陇西产蒙古属黄芪对代谢综合征患者外周血管保护作用及其机制的研究
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摘要
目的观察甘肃陇西产蒙古属黄芪对代谢综合征(MetS)伴高血压病患者外周血管的作用及其对血管紧张素转换酶/血管紧张素转换酶2(ACE/ACE2)蛋白表达水平及血清中8-羟基脱氧鸟苷(8-OHdG)的影响并探讨其可能机制。
     方法应用前瞻性随机对照平行试验设计,将入选148例MetS患者随机分为3组,分别给予内科基础药物治疗(对照组,n=50)、内科基础药物联合高剂量黄芪浸膏胶囊治疗(黄芪1组,10g/d,n=49)以及内科基础药物联合低剂量黄芪浸膏胶囊(黄芪2组,5g/d,n=49)治疗。本研究按试验设计样本量估算,计划纳入患者210例,随访时间为1年,现主要分析半年后部分患者的中期结果。运用高分辨率B型超声仪探查患者颈动脉内膜中层厚度(CIMT)的变化;采用血压脉搏测量仪评价治疗前后患者的心-踝血管指数(CAVI)及踝臂指数(ABI)的变化;应用Western-blot法及Elisa法分别测定治疗前后患者外周血淋巴细胞ACE/ACE2蛋白表达水平及血清中8-OHdG水平的变化;并运用SPSS17.0统计软件对各项数据进行统计学分析。
     结果①与对照组(n=29)比较,半年后黄芪1组(n=28)以及黄芪2组(n=29)ACE2表达水平升高(p=0.000), ACE表达水平降低(p=0.000),但黄芪1组与黄芪2组组间比较无统计学意义(p=0.972);②与基线水平比较,半年后患者CIMT并未得到有效改善(p=0.011);③与对照组比较,黄芪1组以及黄芪2组患者ABI、 CAVI及8-OHdG水平无统计学意义(p>0.05)。
     结论中期分析结果表明,甘肃陇西产蒙古属黄芪对MetS伴高血压病患者的外周血.管功能具有一定的保护作用,这种保护作用的可能机制为黄芪可以调节ACE/ACE2蛋白表达水平;黄芪对MetS患者ABI、CAVI及8-OHdG水平并无明显的影响,但由于上述结果仅为本研究的部分中期结果,病例数及观察时间还未能达到课题的设计要求,各指标的统计学意义仅供参考。因此,本研究仍有待于继续完成,观察其终期结果,以提供更可靠的证据。
     目的系统评价钙通道阻滞剂(CCBs)与血管紧张素转换酶抑制剂(ACE-Is)单一用药与联合治疗对中国高血压(EH)患者左室肥厚(LVH)的疗效和安全性。
     方法计算机检索Cochrane图书馆临床对照试验数据库(2011年第7期)、PubMed (1980~2011)、EMbase (1990~2011)、CBMdisc (1978~2011)、CNKI (1994~2011)、VIP (1989~2011)和WANFANG DATA (1998~2011),严格按照纳入与排除标准选择临床研究。对纳入的临床研究进行质量评价,并用RevMan5.1软件对数据进行Meta分析。
     结果最终纳入10篇临床随机对照试验(RCTs),共859例患者。Meta分析结果显示:CCBs与ACE-Is联合用药组在改善EH患者收缩压[MD=-6.49,95%CI(-10.55,-2.43)]、舒张压[MD=-4.48,95%CI(-6.76,-2.21)]、左室心肌重量指数(LVMI)[MD=-5.31,95%CI(-8.43,-2.19)]、舒张末室间隔厚度(IVST)[MD=-1.33,95%CI(-2.00,-0.66)]和左室后壁厚度(LVPWT)[MD=-0.87,95%CI (-1.41,-0.33)]方面均优于CCBs单药治疗组;此外,与ACE-Is单药治疗组相比,联合用药组在降低LVMI [MD=-11.54,95%CI (-15.06,-8.01)]、IVST [MD=-0.76,95%CI (-1.25,-0.27)]及LVPWT [MD=-0.80,95%CI (-1.01,-0.59)]方面具有明显的优越性;但在左室舒张末内径、左室短轴缩短率及左室射血分数等指标的改善方面,联合用药组与CCBs或ACE-Is单药治疗组的临床效果相当(P>0.05)
     结论联合用药组在逆转左室肥厚方面要优于CCBs或ACE-Is单药治疗组。由于所纳入研究的方法学质量较差,且样本量较少,有必要开展更多高质量、大样本,多中心的RCTs,以提供更可靠的证据。
Objective To study the effect and mechanism of Astragalus Mongholicus on protection of peripheral artery in hypertensive patients with metabolic syndrome (MetS).
     Methods In this prospective, randomized, controlled, parallel clinical trial, we assigned148MetS patients (totally210MetS patients were needed, and the period of follow-up examination were twelve months.) to three groups:Control group(n=50), Astragalus Mongholicus group1(10g/d, n=49) and Astragalus Mongholicus group2(5g/d, n=49), then performed different treatments respectively. We employed high-resolution ultrasonography, blood and pulse measuring instrument respectively to detect their carotid intima-media thickness (CIMT), cardio-ankle vascular index (CAVI) and ankle brachial index (ABI).Serum8-hydroxy-2'-deoxyguanosine (8-OHdG) level and angiotensin converting enzyme/angiotensin converting enzyme2(ACE/ACE2) protein expression levels of human peripheral blood lymphocyte were examined by Elisa and Western-blot. In this paper, intermediate period (six months) data was analyzed.The changes of these indexes were observed, SPSS17.0software was used to statistical analysis the data.
     Results1. Compared with control(n=29), expression level of ACE2in Astragalus Mongholicus group1(n=28) and Astragalus Mongholicus group2(n=29) were significantly upregulated (p=0.000), and the expression level of ACE were significantly downregulated (p=0.000) in six month later, but expression level of ACE and ACE2were similar between the Astragalus Mongholicus group1and the Astragalus Mongholicus group2(p=0.972);2. Compared with baseline, the Astragalus Mongholicus group1and Astragalus Mongholicus group2showed inferior effect to decreasing the CIMT (p=0.011);4.There was no statistically difference in level of ABI, CAVI and serum8-OHdG among these three groups(p>0.05).
     Conclusion The Astragalus Mongholicus of Longxi, Gansu Province, may protect the peripheral artery function partly in hypertensive patients with MetS, and its possible mechanism is that Astragalus Mongholicus might regulate the expression level of ACE and ACE2. Because these data are just middle term results, sample size and intervention time do not meet design requirements. Thus, whether Astragalus Mongholicus has function of vascular protection is still not definite. This study still needs improving the terminal results which should be observed to provide more reliable evidence.
     Purpose A meta-analysis was carried out to compare the effect of calcium channel blockers(CCBs) and angiotensin-converting enzyme inhibitors (ACE-Is) alone and their combination on the reversion of left ventricular hypertrophy(LVH) in Chinese hypertensive patients.
     Methods Retrieved relevant medical database, including Cochrane Library (the seventh issue of2011), PubMed (1980~2011), EMBASE (1980~2011), Chinese Biomedical Literature Database (1978~2011), Chinese Scientific Journals Full-text Database (1994~2011), Chinese Journal Full-text Database (1989~2011) and Wanfang Database (1998~2011). Selected clinical studies were according to predefined inclusion and exclusion criteria, evaluated the quality of included studies.The RevMan5.1software was used to analysis the data.
     Results Ten studies, total859patients were identified. There were statistically significant in SBP (MD=-6.49,95%CI:-10.55,-2.43),DBP (MD=-4.48,95%CI:-6.76,-2.21), left ventricular mass index (LVMI)(MD=-5.31,95%CI:-8.43,-2.19), interventricular septal thickness (IVST)(MD=-1.33,95%CI:-2.00,-0.66) and left ventricular posterior wall thickness (LVPWT)(MD=-0.87,95%CI:-1.41,-0.33) in CCBs and ACE-Is combination versus CCB monotherapy (P<0.05). In addition, compared with ACE-Is monotherapy, the combination treatment showed prior effect on the decreasing of LVMI (MD=-11.54,95%CI:-15.06,-8.01), IVST (MD=-0.76,95%CI:-1.25,-0.27). and LVPWT(MD=-0.80,95%CI:-1.01,-0.59)(P<0.05). The left ventricular end diastolic diameter (LVDd), fraction shortening (FS) and ejection fractions(EF) were no difference in CCBs or ACE-Is mono-therapy and their combination (P>0.05).
     Conclusion The combination therapy with CCBs and ACE-ls is more superior than individual agents in regression of left ventricular hypertrophy. Because of the low methodological quality, further high quality,large, multicenter, RCTs are required to explore the effects of CCBs and ACE-Is combination on LVH in Chinese hypertensive patients.
引文
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