氯沙坦对华法林诱导的大鼠血管钙化的作用研究  

Effects of losartan on warfarin-induced vascular calcification in rats

作　　者：邵娟[1] 李敏才[1] 吴基良[1] 

机构地区：[1]湖北科技学院糖尿病及心脑血管病重点实验室,咸宁437100

出　　处：《中国心血管杂志》2016年第4期300-305,共6页Chinese Journal of Cardiovascular Medicine

基　　金：国家自然科学基金项目(81270355);湖北省自然科学基金项目(2014CFB211)~~

摘　　要：目的观察氯沙坦对华法林诱导的大鼠血管钙化模型的影响,并探讨其可能的作用机制。方法 28只5周龄雄性SD大鼠按随机数字表法分为4组:对照组(C)、模型组(M)、模型+低剂量氯沙坦组(M+L)、模型+高剂量氯沙坦组(M+H)(每组7只)。造模成功后取各组大鼠主动脉进行HE染色和茜素红染色,观察血管壁形态学变化和钙盐沉积情况。实时荧光定量PCR检测缝隙连接蛋白(Cx43)mRNA表达,Western blot检测丝裂原活化蛋白激酶(MAPK)、Cx43和基质Gla蛋白(MGP)表达情况。结果华法林能够诱导大鼠血管钙化模型。与对照组比较,模型组Cx43 mRNA和蛋白表达显著上调(3.98±0.65比1.06±0.31,P<0.01;1.91±0.45比1.03±0.07,P=0.029),MAPK家族中细胞外信号调节激酶(ERK)活性显著增加(1.40±0.19比1.04±0.04,P=0.032),MGP表达显著下降(0.19±0.07比1.00±0.02,P<0.01)。与模型组比较,两种剂量氯沙坦干预组Cx43 mRNA和蛋白表达均显著下调(2.28±0.47比3.98±0.65,P=0.021;1.07±0.24和0.64±0.24比1.91±0.45,P=0.047和0.013),ERK活性显著降低(0.76±0.04和0.69±0.09比1.40±0.19,均为P<0.01),MGP表达显著增加(0.45±0.08和0.83±0.10比0.19±0.07,P=0.013和P<0.01)。结论氯沙坦可以抑制华法林诱导的大鼠血管钙化,可能与下调Cx43表达及ERK活性,增加MGP表达有关。Objective To investigate the effects and mechanism of losartan regulating vascular calcification in rat vascular calcification models induced by warfarin. Methods Twenty eight 5-week-old male Sprague-Dawley （SD） rats were randomly divided into 4 groups：Control （C）,Model （M）,Model＋Low losartan （M ＋L）,Model＋High losartan （M ＋H）. Vascular calcification was confirmed by HE and Alizarin Red staining to observe morphology and calcium deposition of vascular wall. The expression of Connexin43 （Cx43） mRNA was detected by real-time quantitative PCR. The expression of mitogen-activated protein kinase （ MAPK） ,Cx43 and Matrix Gla Protein （ MGP） were analyzed by western blot. Results The vascular calcification could be induced by warfarin in rats. Compared with C group,The expressions of Cx43 mRNA and protein in aorta in model group were up-regulated significantly （3. 98 ± 0. 65 vs. 1. 06 ± 0. 31, P＆lt;0. 01;1. 91 ± 0. 45 vs. 1. 03 ± 0. 07, P =0. 029 ） . Meanwhile, the extracellular signal-regulated kinase （ ERK） activity was significantly increased （1. 40 ± 0. 19 vs. 1. 04 ± 0. 04,P=0. 032） and the expression of MGP was significantly decreased （0. 19 ± 0. 07 vs. 1. 00 ± 0. 02,P〈0. 01）. Compared with M group,The expression of Cx43 mRNA and protein of aorta in M＋L and M＋H group were down-regulated significantly （2. 28 ± 0. 47 vs. 3. 98 ± 0. 65,P=0. 021;1. 07 ± 0. 24 and 0. 64 ± 0. 24 vs. 1. 91 ± 0. 45,P =0. 047 and 0. 013） and ERK activity was significantly decreased （0. 76 ± 0. 04 and 0. 69 ± 0. 09 vs. 1. 40 ± 0. 19,both P〈0. 01 ） . Meanwhile, the expression of MGP was significantly increased （ 0. 45 ± 0. 08 and 0. 83 ± 0. 10 vs. 0. 19 ± 0. 07,P=0. 013 and P〈0. 01）. Conclusions Warfarin-induced vascular calcification in rats could be suppressed by losartan. The mechanism may be related with inhibition of Cx43 expression and ERK activation,and increased MGP expression.

关 键 词：氯沙坦 血管钙化 缝隙连接蛋白43 细胞外信号调节MAP激酶类 基质GLA蛋白 CONNEXIN 43 

分 类 号：R54[医药卫生—心血管疾病]