Moriguchi Yoshiyuki, Yogo Kenji, Aizawa Ken, Serizawa Ken-Ichi, Tashiro Yoshihito, Yorozu Keigo, Ishizuka Nobuhiko, Iwabuchi Sadahiro, Kitamura Hidemitsu, Nishimura Takashi
Product Research Department, Chugai Pharmaceutical Co., LTD.
Biomed Res. 2011 Apr;32(2):83-90. doi: 10.2220/biomedres.32.83.
The pathological influences of inflammation on left ventricular hypertrophy (LVH) were studied in subtotal nephrectomized (SNx) rats after 0.3% NaCl loading for 5 weeks. We found that mild hypertension, increased plasma levels of creatinine, inorganic phosphate, asymmetric dimethylarginine (ADMA), and parathyroid hormone (PTH) were observed in the present SNx rats without LVH. In the present study, the NaCl-loaded SNx (SNx + NaCl) rats were characterized by significant LVH and hypertension with aggravated values of all the parameters. We further confirmed that glomerular sclerosis, tubulointerstitial fibrosis, and inflammatory cell infiltration into the tubulointerstitial area, observed in the SNx rats, were more severely caused in the SNx + NaCl rats. In addition, plasma interleukin-6 (IL-6) levels in the SNx + NaCl rats were significantly increased compared to those in the SNx rats. These findings indicated that NaCl-loaded SNx rats developed LVH and hypertension, which were accompanied with increased plasma levels of PTH, creatinine, inorganic phosphorus, ADMA, and IL-6. Thus, these results suggest that inflammation as well as endothelial dysfunction would be correlated with LVH as non-traditional risk factors at the early stage in the present renal failure model.
在接受0.3%氯化钠负荷5周的次全肾切除(SNx)大鼠中,研究了炎症对左心室肥厚(LVH)的病理影响。我们发现,在本研究的无LVH的SNx大鼠中观察到轻度高血压、血浆肌酐、无机磷酸盐、不对称二甲基精氨酸(ADMA)和甲状旁腺激素(PTH)水平升高。在本研究中,氯化钠负荷的SNx(SNx + NaCl)大鼠的特征是显著的LVH和高血压,所有参数值均加重。我们进一步证实,在SNx大鼠中观察到的肾小球硬化、肾小管间质纤维化以及炎症细胞浸润到肾小管间质区域,在SNx + NaCl大鼠中更为严重。此外,与SNx大鼠相比,SNx + NaCl大鼠的血浆白细胞介素-6(IL-6)水平显著升高。这些发现表明,氯化钠负荷的SNx大鼠出现了LVH和高血压,同时伴有血浆PTH、肌酐、无机磷、ADMA和IL-6水平升高。因此,这些结果表明,在本肾衰竭模型的早期阶段,炎症以及内皮功能障碍可能作为非传统危险因素与LVH相关。