摘要
目的 观察TGFβ-Smads传导通路在自发性高血压大鼠心肌纤维化形成中的作用机制及其卡托普利的调控作用.方法 取15周龄雄性自发性高血压大鼠20只,随机均分为模型组及卡托普利组;另取10只同龄健康雄性WKY大鼠作为正常对照组.卡托普利组给予45mg/kg卡托普利灌胃,模型组、正常对照组给予等量0.9%氯化钠溶液灌胃,2次/d,疗程为12周.12周后,采用ELISA法检测血清Ⅰ、Ⅲ型胶原;采用半定量RT-PCR法检测转化生长因子β1（TGFβ1）的表达;免疫组化检测Smad2/3及Smad7的表达.结果 与正常对照组比较,模型组大鼠心肌Ⅰ、Ⅲ型胶原及TGFβ1、Smad2/3的表达均明显升高（均P＜0.05）,Smad7的表达明显降低（P＜0.05）;与模型组比较,卡托普利组大鼠心肌Ⅰ、Ⅲ型胶原及TGFβ1、Smad2/3的表达均明显降低（均P＜0.05）,Smad7的表达明显升高（P＜0.05）.结论 自发性高血压大鼠TGFβ-Smad通路的激活可能是导致其心肌组织中Ⅰ、Ⅲ型胶原表达增高从而形成心肌纤维化的机制之一;卡托普利具有抑制高血压所导致的心肌纤维化的作用.
Objective To investigate the role that TGF β-smads signal transduction pathway in myocardial fibrosis （MF） of spontaneous hypertension rats （SHR） and the effect of captopril. Methods Twenty 15-week-old male SHR rats were divided into two groups randomly;model group （n= 10） and captopril group （n= 10）; other ten 15-week-old male Wistar Kyoto rats served as the controls. The rats of captopril group were treated with 45mg/kg captoprit by gastric gavage for 12 weeks; the rats in model group were given the same amount of normal saline. Serum PINP and PIIINP were measured by ELISA; TGF β1 gene expression were detected by RT-PCR; and the protein expression of smad2/3 and smad7 were detected by immunohistochemistry. Results Serum levels of PINP and PIIINP, the expression of TGFβ were increased in model group. The expression of smad2/3 in model group was higher than that in control group （P〈0.05）, but the expression of smad7 was lower than that in control group（P〈0.05 ）. Comparing to model group the PINP, PIIINP levels and expression of TGF β 1 and smad2/3 in captopril group were decreased （ all P 〈 0.05）, the expression of smad7 was increased （P 〈 0.05）. Conclusion The activation of TGF β -smads signal transduction pathway and increase of serum PINP and PIIINP levels may be associated with myocardial fibrosis in SHR. Captopril can lower the expression of the PINP and PilINP and restrain myocardial fibrosis.
出处
《浙江医学》
CAS
2011年第3期319-321,共3页
Zhejiang Medical Journal
