Zhang M-J, Gu Y, Wang H, Zhu P-F, Liu X-Y, Wu J
Department of Cardiology, Wuhan Puai Hospital, Huazhong University of Science and Technology, Wuhan, China.
Eur Rev Med Pharmacol Sci. 2016;20(2):345-54.
Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a β-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model.
Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal.
Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment.
Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.
主动脉腔静脉瘘（AV）可导致伴有轻度肾功能不全（右肾切除：UNX）的大鼠出现慢性容量超负荷，进而模拟4型心肾综合征（CRS）：慢性肾心综合征。半乳糖凝集素-3是一种β-半乳糖苷结合凝集素，是心血管疾病和肾脏疾病中一种新兴的生物标志物。我们观察了缬沙坦对该模型中心脏和肾脏肥大以及半乳糖凝集素-3变化的影响。
将成年雄性Sprague-Dawley（SD）大鼠（200-250 g）分为S组（假手术组，n = 7）、M组（UNX+AV组，n = 7）和M+V组（UNX+AV+缬沙坦组，n = 7）。8周后，通过超声心动图测量心脏功能。通过肾小球滤过率、有效肾血浆流量、肾血流量和24小时蛋白尿来评估肾脏结局。采用免疫组织化学和实时PCR评估心脏和肾脏中半乳糖凝集素-3的表达。
在这种伴有轻度肾功能不全的AV分流诱导的慢性容量超负荷大鼠模型中，证实存在心脏肥大、肾脏肥大以及心脏扩大。心脏和肾脏肥大明显减轻，但缬沙坦对心脏扩大无影响，且与其降压作用无关。该模型中24小时尿白蛋白显著增加，而缬沙坦可使其显著降低。免疫组织化学和实时PCR证实心脏和肾脏中半乳糖凝集素-3表达显著上调，心肌Ⅰ型胶原表达略有增加，缬沙坦治疗后其表达趋于降低。
半乳糖凝集素-3信号上调可能也参与了该CRS模型的发病机制。缬沙坦在减轻该模型中心脏和肾脏肥大以及降低24小时白蛋白方面的有益作用可能部分是通过下调半乳糖凝集素-3信号通路介导的。
