Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model.
Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model.
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肾素-血管紧张素-醛固酮系统抑制剂替米沙坦和丝氨酸蛋白酶抑制剂甲磺酸卡莫司他的联合治疗在大鼠慢性肾病模型中提供了进一步的肾脏保护作用。
DOI：
10.1016/j.jphs.2016.01.003
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发表时间：
2016
影响因子：
3.5
通讯作者：
Kenichiro Kitamu
中科院分区：
文献类型：
--
作者：
Yuki Narita;Miki Ueda;Kohei Uchimura;Yutaka Kakizoe;Yoshikazu Miyasato;Teruhiko Mizumoto;Jun Morinaga;Manabu Hayata;Terumasa Nakagawa;Masataka Adachi;Taku Miyoshi;Yoshiki Sakai;Daisuke Kadowaki;Sumio Hirata;Masashi Mukoyama;Kenichiro Kitamu
我们以前报道过甲磺酸卡莫司坦(CM)对CKD模型大鼠的肾脏保护和降压作用。在这项研究中，我们研究了CM是否与肾素-血管紧张素-醛固酮系统(RAS)抑制剂替米沙坦(TE)对CKD的进展有明显的肾脏保护作用。我们评价了中药(400 mg/kg/d)和/或TE(10 mg/kg/d)对腺嘌呤诱导的大鼠CKD模型肾功能、氧化应激、肾纤维化和RAS成分的影响。与单独用药相比，CM和TE联合治疗显著降低了腺嘌呤引起的血清肌酐水平的升高，尽管所有治疗组的血压都有类似的降低。类似地，腺嘌呤诱导的氧化应激标记物和肾纤维化标记物的升高通过联合治疗相对于单独治疗显著减少。此外，联合用药对血浆肾素活性(PRA)和血浆醛固酮浓度(PAC)的影响与TE单药相似，而CM对PRA和PAC均无影响，提示CM具有与RAS抑制作用不同的药理作用。我们的研究结果表明，CM可能成为接受RAS抑制剂治疗的CKD患者的附加治疗的候选药物。
We previously reported that camostat mesilate (CM) had renoprotective and antihypertensive effects in rat CKD models. In this study, we examined if CM has a distinct renoprotective effect from telmisartan (TE), a renin-angiotensin-aldosterone system (RAS) inhibitor, on the progression of CKD. We evaluated the effect of CM (400 mg/kg/day) and/or TE (10 mg/kg/day) on renal function, oxidative stress, renal fibrosis, and RAS components in the adenine-induced rat CKD model following 5-weeks treatment period. The combination therapy with CM and TE significantly decreased the adenine-induced increase in serum creatinine levels compared with each monotherapy, although all treatment groups showed similar reduction in blood pressure. Similarly, adenine-induced elevation in oxidative stress markers and renal fibrosis markers were significantly reduced by the combination therapy relative to each monotherapy. Furthermore, the effect of the combination therapy on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was similar to that of TE monotherapy, and CM had no effect on both PRA and PAC, suggesting that CM has a distinct pharmacological property from RAS inhibition. Our findings indicate that CM could be a candidate drug for an add-on therapy for CKD patients who had been treated with RAS inhibitors.