Rumble J R, Gilbert R E, Cox A, Wu L, Cooper M E
Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Australia.
J Hypertens. 1998 Nov;16(11):1603-9. doi: 10.1097/00004872-199816110-00006.
The purpose of this study was to assess the role of transforming growth factor (TGF)-beta1 in the development of diabetes-associated mesenteric vascular hypertrophy and in the antitrophic effect of angiotensin converting enzyme inhibitors.
Streptozotocin-induced diabetic and control Sprague-Dawley rats were randomly allocated to treatment with the angiotensin converting enzyme inhibitor ramipril or to no treatment and were killed 1 or 3 weeks after the streptozotocin injection. Blood was collected and mesenteric vessels removed. Mesenteric vascular weight was measured and TGF-beta1 and alpha1 (type IV) collagen messenger (m)RNA levels were analysed by Northern analysis. Immunohistochemical analyses for TGF-beta1 and type IV collagen were also performed.
The diabetic rats had increased mesenteric vessel weight at 3 weeks but not at 1 week and a concomitant rise in mesenteric TGF-beta1 and in alpha1 (type IV) collagen mRNA levels. Ramipril treatment attenuated mesenteric vessel hypertrophy and prevented the increase in TGF-beta1 and alpha1 (type IV) collagen mRNA levels after 3 weeks of diabetes. The immunohistochemical analysis revealed that diabetes was associated with increased TGF-beta1 and type IV collagen protein and extracellular matrix accumulation in mesenteric vessels, and this increase was reduced by ramipril treatment.
These results support the concept that TGF-beta is involved in the changes associated with diabetic vascular disease, and suggest a mechanism by which angiotensin converting enzyme inhibitors exert their antitrophic effects.
本研究旨在评估转化生长因子（TGF）-β1在糖尿病相关肠系膜血管肥大发展过程中的作用以及血管紧张素转换酶抑制剂的抗肥大作用。
将链脲佐菌素诱导的糖尿病大鼠和对照Sprague-Dawley大鼠随机分为接受血管紧张素转换酶抑制剂雷米普利治疗组或不治疗组，并在注射链脲佐菌素后1周或3周处死。采集血液并取出肠系膜血管。测量肠系膜血管重量，通过Northern印迹分析检测TGF-β1和α1（IV型）胶原信使（m）RNA水平。还进行了TGF-β1和IV型胶原的免疫组织化学分析。
糖尿病大鼠在3周时肠系膜血管重量增加，但1周时未增加，同时肠系膜TGF-β1和α1（IV型）胶原mRNA水平升高。雷米普利治疗减轻了肠系膜血管肥大，并阻止了糖尿病3周后TGF-β1和α1（IV型）胶原mRNA水平的升高。免疫组织化学分析显示，糖尿病与肠系膜血管中TGF-β1和IV型胶原蛋白增加以及细胞外基质积聚有关，而雷米普利治疗可减少这种增加。
这些结果支持TGF-β参与糖尿病血管疾病相关变化的观点，并提示血管紧张素转换酶抑制剂发挥其抗肥大作用的机制。
