摘要
目的:研究替米沙坦对肝硬化患者门静脉的血流动力学及肝纤维化程度的影响及机制。方法:80例肝硬化患者随机分为对照组和治疗组各40例,对照组给予常规治疗,治疗组在此基础上加用替米沙坦80mg.d-1,疗程1个月。2组患者治疗前后应用彩色多普勒超声仪检测门、脾静脉的内径与流速,同时采用放免法检测血降钙素基因相关肽(CGRP)、透明质酸(HA)的水平,酶联免疫法测定血转化生长因子β1(TGFβ1)、血小板源性生长因子(PDGF)的水平,RT-PCR检测过氧化物酶体增生物活化受体γ(PPARγ)mRNA水平。结果:对照组患者治疗后血清PPARγmRNA、CGRP、HA、TGFβ1、PDGF水平以及门、脾静脉的内径与流速无显著性变化(P>0.05)。替米沙坦治疗后,患者血清PPARγmRNA水平升高(P<0.05),CGRP、TGFβ1、PDGF和HA水平下降(P<0.05),门、脾静脉的内径减小,平均流速增快(P<0.05)。结论:替米沙坦不仅可通过阻断血管紧张素Ⅱ的生物活性、上调PPARγ水平,抑制TGFβ1、PDGF表达而发挥抗肝纤维化作用,而且可通过降低血清CGRP水平及抗肝纤维化作用而降低门静脉压力。
OBJECTIVE To study the effects and mechanism of action of telmisartan on portal hemodynamics and degree of hepatic fibrosis in patients with hepatic cirrhosis, METHODS Eighty patients with hepatic cirrhosis were divided into control group and treatment group. Forty patients in control group received routine treatment for 1 month and forty patients in treat- ment group received telmisartan 80 mg/d based on routine treatment for the same time. Diameter of portal or splenic vein and their mean velocity were measured before and after treatment by color Doppler. Blood serum levels of calcitonin gene related peptide （CGRP） and hyaluronic acid （HA） were simuhaneously assessed by radioimmunoassay. Blood serum levels of transfor- ming growth factor β1（TGFβ1）and platelet-derived growth factor（PIXSF） were measured by ELISA. Blood serum level of peroxisome proliferator-activated receptor γ mRNA （PPARγ mRNA） was measured by RT PCR. RESULTS There was no difference on the expression of PPARγ mRNA, CGRP, HA,TGFI31 and PDGF before and after treatment in control group（P〉 0. 05）. The diameter of portal or splenic vein and the mean velocity of portal or splenic vein in control group had no significant diversity before and after treatment （P〉0. 05）. Telmisartan heighten the expression of PPAR）＇ mRNA and reduced the con- centrations of CGRP, HA, TGβ1 and PDGF（P〈0.05）. It also reduced the diameter of portal or splenic vein and increased the mean velocity of portal or splenic vein（P〈0. 05）. CONCLUSION Telmisartan has the effect of anti-hepatic fibrosis. Its mech- anism of action is telmisartan can activate PPARy as well as blocking the biological activity of angiotensin II and suppress the expression of TGFβ1, PDGF. It also may reduce portal hypertension through reducing the concentration of CGRP as well as the effect of anti-hepatic fibrosis.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2010年第21期1845-1848,共4页
Chinese Journal of Hospital Pharmacy
