TGF-β_1/Smads和ERK表达异常在高盐饮食诱导的大鼠血管重构中的作用  

Role of TGF-β_1/Smads and ERK expression in vascular remodeling induced by high-salt diet in Wistar rats

作　　者：刘婵[1] 商黔惠[1,2] 闵晓强[1] 陈剑玲[2] 毛万姮[1] 

机构地区：[1]遵义医学院临床医学研究所,贵州遵义563000 [2]遵义医学院附属医院心内科,贵州遵义563000

出　　处：《中国病理生理杂志》2012年第10期1766-1772,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81160041);贵州省社会发展攻关计划项目和省高层次人才科研条件特助项目[No.黔科合SY字(2011)3047号;TZJF-2009年-42]

摘　　要：目的:研究转化生长因子β1(TGF-β1)/Smads和细胞外信号调节激酶(ERK)表达在高盐饮食诱导的大鼠血管重构中的作用及替米沙坦的干预效应。方法:雄性Wistar大鼠随机分为正常盐对照组(C组),8%高盐模型组和8%高盐+替米沙坦干预组(T组),每2周测量尾动脉压1次,根据尾动脉压又将8%高盐模型组分为模型高血压组(MH组)和模型正常血压组(MN组),喂养共24周。HE染色和Masson染色观察主动脉和肠系膜动脉重构。通过real-time PCR测定主动脉中膜TGF-β1、Smad2和Smad3和Smad7 mRNA表达,同时免疫组化法检测主动脉和肠系膜动脉中膜增殖细胞核抗原(PCNA)、TGF-β1、磷酸化Smad2/3(p-Smad2/3)、磷酸化ERK1/2(p-ERK1/2)及Smad7的蛋白表达和分布。结果:与C组相比,MH组大鼠血压升高(P<0.05),MH组和MN组主动脉和肠系膜动脉中膜胶原容积分数(CVF)和中膜厚度(MT)显著增加(P<0.01),主动脉TGF-β1、Smad2和Smad7 mRNA表达增高(P<0.05),主动脉和肠系膜动脉中膜PCNA、TGF-β1、p-Smad2/3和p-ERK 1/2蛋白表达显著升高(P<0.05),Smad7表达明显降低(P<0.05);经替米沙坦干预后,主动脉和肠系膜动脉中膜CVF和MT减小(P<0.01),PCNA、TGF-β1、p-Smad2/3和p-ERK1/2表达减少(P<0.05),Smad7表达上升(P<0.05)。结论:TGF-β1/Smads和ERK表达异常共同参与高盐饮食致主动脉和肠系膜动脉重构的机制;替米沙坦抗动脉重构的作用可能部分是通过阻断血管紧张素Ⅱ1型(AT1)受体影响TGF-β1/Smads和ERK表达实现的。AIM： To investigate the role of transforming growth factor β1 （TGF - β1 ）/Smads and extracellular signal - regulated kinase（ERK） expression in vascular remodeling induced by high - salt diet in Wistar rats. METHODS： Wistar rats were randomly divided into 3 groups： normal control group （n = 13）, high salt （8%） model group and high salt ＋ telmisartan group （n = 13）. Tail - cuff arterial pressure was determined every 2 weeks. After 24 weeks, the rats in high salt model group were divided into model animals with hypertension group （MH, n = 12） and model animals without hypertension group （MN, n = 12）. The remodeling of aorta and mesenteric artery was observed by HE and Masson stai- ning. In addition, the techniques of immunohistochemistry and real - time PCR were applied to detect the expression of proliferating cell nuclear antigen （ PCNA）, TGF- β1, P - Smad2/3, p - ERK1/2 and Smad7 at both protein and mRNA levels. RESULTS： Compared with normal control group, blood pressure in MH group was much higher, and media thick- ness （MT） and collagen volume fraction （CVF） of arteries in MH and MN groups were higher. The mRNA expression of TGF -β, Smad2 and Smad7 in the aorta was significantly increased, and the protein levels of PCNA, p - ERK1/2, TGF -β1 and p -Smad2/3 in the aorta and mesenteric artery media were elevated, but Smad7 decreased. After telmisartan treatment, MT and CVF were much lower, and the protein levels of PCNA, TGF -β1, P - Smad2/3 and p - ERK1/2 were significantly reduced, whereas Smad7 was increased. CONCLUSION： The abnormal expression of TGF- β1/Smads and ERK may be involved in the mechanism of remodeling of aorta and mesenteric artery induced by high - salt diet. Telmisartan prevents the vascular remodeling via regulating TGF - β1Smads and ERK signal pathways mediated by angiotensin II type 1 （AT1 ） receptor, at least in part.

关 键 词：高盐饮食 血管重构 转化生长因子β1 Smad蛋白类 细胞外信号调节激酶 

分 类 号：R363[医药卫生—病理学]