充血性心力衰竭肾脏致纤维机制的研究

Study on possible mechanisms of renal fibrotic effect in experimental congestive heart failure

目的 观察不同程度充血性心力衰竭时肾脏转移生长因子 β1(TGF β1)和纤维结合素 (FN)的改变以及血管紧张素转换酶抑制剂福辛普利对其的影响。方法 将SD大鼠通过腹主动脉 下腔静脉穿刺造瘘和冠状动脉结扎的方法建成不同的心力衰竭模型 ,并对冠状动脉结扎大鼠予福辛普利治疗。通过Doppler超声心动图比较心功能的各项参数 ,并采用免疫组织化学和逆转录 聚合酶链式反应 (RT PCR)方法检测肾脏TGF β1和FN的基因和蛋白表达。结果 穿刺造瘘大鼠的心功能损害较轻。而冠状动脉结扎大鼠心功能严重失代偿。福辛普利可以部分缓解冠状动脉结扎大鼠的心肌肥厚和受损的心功能。两组心力衰竭大鼠肾脏TGF β1的基因和蛋白水平以及FN的蛋白表达明显增强 (P <0 .0 0 1)。福辛普利能显著改善冠状动脉结扎大鼠肾脏TGF β1和FN表达的异常。结论 充血性心力衰竭早期即出现肾脏TGF β1和FN的表达增加 ,福辛普利通过下调其表达 。

Objective To investigate the changes of renal expression of transforming growth factor β 1 (TGFβ 1) in rats with different degree of congestive heart failure(CHF) and the impact of angiotensin converting enzyme inhibitor Fosinopril at the same time. Methods To establish different degree of congestive heart failure animal models with abdominal aortocaval shunts (A) and ligature of the left coronary artery (L) respectively in SD rats. Fosinopril was given orally to the ligature rats at a dose of 25 mg·kg -1 ·d -1 since the next day of intervention (F). Cardiac function was detected with Doppler echocardiography. Gene expression of TGF β 1 in the kidney was detected by RT PCR. Simultaneously, protein expressions and distribution of TGF β 1 and fibronectin (FN) in the kidney were assessed with immunohistochemistry staining. Results Cardiac function of aortocaval shunt rats deteriorated to a lesser extent, whereas that of the ligature rats (L) was severely decompensated. Fosinopril could partially ameliorate the impaired cardiac function in ligature rats as well as reduce the myocardial hypertrophy and increase EF significantly. RT PCR and immunohistochemistry staining revealed a significant increase in TGF β 1 and FN expression in the two groups of CHF animals, even if their renal histologic examination still remained normal. Fosinopril could significantly improve these changes in ligature rats. Conclusion There is a significant increase in renal expression of TGF β 1 and FN in early CHF. Fosinopril may be helpful in preventing the onset and progression of nephropathy, probably through down regulating the expression of TGF β 1.