自发性高血压大鼠心肌组织microRNA-133a与TGF-β1蛋白表达的改变及意义

 目的：观察microRNA-133a（miR-133a）与转化生长因子-β1（transforming growth factor β1，TGF-β1）蛋白在自发性高血压大鼠（spontaneously hypertensive rats，SHR）心肌组织中的表达改变和关系。方法：取12只18周龄雄性自发性高血压大鼠为SHR组，12只18周龄雄性Wistar-Kyoto （WKY）大鼠为对照组，通过无创血压测量分析系统测大鼠尾动脉血压，Masson染色检测心肌胶原容积分数（collagen volume fraction，CVF）和血管周围胶原面积比率（perivascular collagen area ratio， PVCA），实时荧光定量PCR检测miR-133a表达水平，免疫组化和Western blotting法检测心肌TGF-β1蛋白表达。结果：与对照组比较，SHR组的收缩压和舒张压明显升高（P<0.01），心肌CVF和PVCA明显升高（P<0.01），TGF-β1蛋白表达水平明显升高（P＜0.01），miR-133a表达水平明显降低（P<0.01），SHR组心肌miR-133a表达水平为对照组的（23.9±4.6）%；SHR组心肌组织miR-133a与TGF-β1蛋白表达水平呈负相关（r=-0.791， P<0.01）。结论：SHR心肌组织miR-133a表达下调，伴随TGF-β1蛋白表达升高和胶原合成增加。miR-133a与TGF-β1可能参与SHR大鼠的心肌纤维化。

Relationship of microRNA-133a and TGF-β1 protein in myocardial tissues of spontaneously hypertensive rats

AIM：To observe the changes of microRNA-133a and transforming growth factor β1 (TGF-β1) protein in the myocardium of spontaneously hypertensive rats (SHR). METHODS：Male SHR (18 weeks old, n=12) and male Wistar-Kyoto rats (WKY, 18 weeks old, n=12) served as SHR group and control group, respectively. Caudal arterial blood pressure was detected by a noninvasive blood pressure measurement and analysis system. Myocardial collagen volume fraction (CVF) and perivascular collagen area ratio (PVCA) were determined by Masson staining. The level of miR-133a in the heart was detected by real-time quantitative PCR. The protein level of TGF-β1 in the heart was also analyzed by the methods of immunohistochemisty and Western blotting. RESULTS：Compared with control group, systolic and diastolic blood pressure, CVF and PVCA significantly increased, the expression of TGF-β1 protein was significantly up-regulated, and the level of miR-133a was significantly reduced  in SHR group. In SHR group, the expression of miR-133a was decreased to (23.9±4.6)% in control group. A negative correlation between the levels of miR-133a and TGF-β1 protein in SHR group was observed (r=-0.791, P<0.01). CONCLUSION：The level of miR-133a is down-regulated along with the up-regulation of TGF-β1 protein expression and collagen synthesis in the myocardial tissues of SHR. miR-133a and TGF-β1 may be involved in myocardial fibrosis in SHR.