转化生长因子βⅡ型受体在糖尿病大鼠血管损伤后的表达及氯沙坦对其调节作用  

Expression of transformation growth factor-β type Ⅱreceptor in injured vessels in diabetic rats and the modulation of losartan

作　　者：郑丽丽[1] 李成光[2] 傅向华[3] 王建功 蒋晓钦 王筠[2] 叶启霞[2] 华海婴[2] 

机构地区：[1]郑州大学第一附属医院内分泌科,450052 [2]郑州大学医学院 [3]河北医科大学第二医院干部病房 [4]解放军460医院心内科

出　　处：《中华心血管病杂志》2003年第4期285-288,共4页Chinese Journal of Cardiology

摘　　要：目的　观察转化生长因子 βⅡ型受体 (TGF βⅡR)在糖尿病鼠血管损伤后血管平滑肌细胞 (VSMCs)和血管壁中的表达及血管紧张素Ⅱ 1型受体拮抗剂氯沙坦对其调节作用。方法　 ( 1)Wistar大鼠单次腹腔注射链脲佐菌素成糖尿病模型后被随机分为糖尿病组和氯沙坦组 ,每组 8只。16只正常鼠随机分为正常对照组和手术对照组。除正常对照组外 ,全部动物均行胸主动脉至左髂总动脉球囊损伤 ,氯沙坦组用氯沙坦 2 0mg·kg- 1 ·d- 1 灌胃 ,余两组均用等量蒸馏水灌胃。 ( 2 )观察实验前、后各组血糖变化和测定动脉壁血管紧张素Ⅱ (AngⅡ )含量。 ( 3)用RT PCR及Northern印迹杂交测定VSMCsTGF βⅡR和Ⅰα(Ⅳ )前胶原mRNA的表达。 ( 4)用免疫组化检测TGF βⅡR和Ⅰα(Ⅳ )前胶原在血管壁的表达。结果　 ( 1)与手术对照组相比 ,糖尿病组AngⅡ含量、TGF βⅡR和Ⅰα(Ⅳ )前胶原mRNA和蛋白水平表达均增高 (P <0 0 1) ,而手术对照组又明显高于正常对照组 (P <0 0 1)。 ( 2 )与手术对照组相比 ,氯沙坦治疗后可明显降低动脉壁AngⅡ含量 ,TGF βⅡR和Ⅰα(Ⅳ )前胶原mRNA、蛋白水平的表达分别被抑制达 6 0 %、5 7%、6 2 %、46 %。结论　糖尿病血管损伤后再狭窄的形成与TGF βⅡRmRNA和蛋白的过度表达有关 ,氯沙坦对其有抑制作?Objective To investigate the expression of transformation growth factor-β type Ⅱreceptor (TGF-βⅡR) in injured vessels in diabetic rats and the modulation of losartan. Methods Sixteen Wistar rats were served with stretozotocin (STZ) 60 mg/kg each rat by intraperitoneal injection. After that, they were randomly divided into diabetic + angioplasty group (diabetic group) and diabetic+angioplasty +losartan therapy group (losartan group), 8 rats in each group. Another 16 rats were randomly divided into normal control group and angioplasty control group. All rats were treated with balloon denudation from thoracic to left iliac aorta. Losartan was administrated by gavage with a dose of 20 mg·kg -1·d -1 during the period of 7 days before operation to 14 days after operation in losartan group. Thoracic aortae were collected to detect:(1) Vascular smooth muscle cells (VSMCs) TGF-βⅡR,Ⅰα(Ⅳ)procollagen mRNA expression with RT-PCR and Northern blot; (2) aortae wall AngⅡconcentration; (3) the protein expression of VSMCs TGF-βⅡR, Ⅰα(Ⅳ)procollagen with immunohistochemistry. Results (1) AngⅡconcentration, TGF-βⅡR and Ⅰα(Ⅳ)procollagen mRNA as well as protein expression were significantly higher in diabetes group than that in angioplasty control group,which was markedly higher in angioplasty control group than that in normal control group (P<0.01). (2)Administration of losartan could reduce AngⅡconcentration, it also could suppress TGF-βⅡR, Ⅰα(Ⅳ)procollagen mRNA and protein expression by 60%, 57%, 62%,46% respectively.Conclusion These findings indicated that there was an interaction between TGF-βⅡR and the pathogenesis of restenosis in injured vessels in diabetic group. Losartan can inhibit the expression of TGF-βⅡR in vascular wall.

关 键 词：转化生长因子βⅡ型受体 糖尿病 大鼠 血管损伤 血管平滑肌细胞 氯沙坦 

分 类 号：R587.1[医药卫生—内分泌] R977.15[医药卫生—内科学]