实验性糖尿病鼠大血管病变TGF-β1和 CTGF的表达及中药的干预作用

Expression of TGF-β1 and CTGF in rats with experimental diabetic macroangiopathy and intervention role of traditional Chinese medicine

关键词:  2型糖尿病  大血管病变  纤维化  中药  结缔组织生长因子  转化生长因子-β1  免疫组化

Key words:  diabetes mellitus 2 macroangiopathy  macroangiopathy fibrosis  traditional Chinese medicine  CTGF  TGF-β1  immunohistochemistry

摘要:

[目的] 通过观测实验性糖尿病鼠大血管病变中转化生长因子(TGF-β1)和结缔组织生长因子(CTGF)相关表达,揭示糖尿病大血管病变的发病机制。并通过中药干预的观察,明确中药在预防和治疗糖尿病大血管病变的靶点。[方法] 雄性SD大鼠80只,其中正常对照组10只,70只造糖尿病模型并随机分为5组:模型组(n=14),中药高、中、低剂量组(n=14),二甲双胍组(n=14).6组大鼠均予普通饲料加干预喂养12周后,取股动脉,应用免疫组化法观察糖尿病(DM)大鼠大血管中CTGF、TGF-β1表达的部位及其变化。[结果] TGF-β1主要在胞浆中表达。模型组TGF-β1表达呈强阳性反应,中药干预组TGF-β1表达明显下降 (P<0.01),二甲双胍对TGF-β1表达有影响,但与中药高剂量组比较差异具有统计学意义(P<0.05).CTGF在模型组血管管壁下层细胞浆可见大量棕黄色物质表达呈强阳性反应,各药物干预组血管细胞CTGF表达都明显下降(P<0.01),中药高剂量组与西药对照组表达比较差异有统计学意义。[结论] 1)糖尿病大血管病变可能与纤维化有关。2)中药组方加味桃核承气汤能有效降低致纤维化因子TGF-β1、CTGF在实验性糖尿病鼠大血管病变中的表达。其对DM大血管病变有改善作用,并存在剂量依赖关系。

Abstract:

[Objective] To explore the pathogenesis mechanism of macroangiopathy in diabetic patients trough observing the expression of TGF-β1 and CTGF in rats with experimental diabetic macroangiopathy and decide the target in preventing and treating the macroangiopathy in patients with diabetes through observing the preventing effect of TCM. [Methods] Among eighty male SD rats seventy were induced with diabetes (DM). They were divided into 5 groups: model group (n=14), high, medium and low dose of traditional Chinese medicine groups (n=14), melbine group (n=14). All rats in these six groups were giving with ordinary feed for 12 weeks. After that, arteria cruralis was obtained and the site and change of expression of CTGF and TGF-β1 in which were observed. [Results] TGF-β1 was mainly expressed in the cytoplasm. It is strong positive in model group. In Chinese medicine intervention groups the expression of TGF-β1 was declined obviously (P<0.01). Melbine has influence on the expression of TGF-β1, but the comparison with high dose of traditional Chinese medicine group has significant difference (P<0.05). A large of brown-1yellow material with strong positive reaction (CTGF) could be seen in cytochylema in submucosa of blood vessels of model group. But the CTGF expression was all significantly lowered in cell of blood vessels in drug intervention groups (P<0.01). The difference of expression between high dose group and Western medicine control group was statistically different. [Conclusion] 1)The onset of diabetic angiopathy may be concerned with fibrosis. 2)Modified Taohe Chengqi Decoction can reduce the expression of Fibrosis factor TGF-β1 and CTGF in rats with experimental diabetic macroangiopathy. It can improve macroangiopathy in DM and has a dose-1dependent relationship.