Ahn Kyung Ohk, Lim Sun Woo, Yang Hyun Joo, Li Can, Sugawara Akira, Ito Sadayoshi, Choi Bum Soon, Kim Yong Soo, Kim Jin, Yang Chul Woo
Department of Internal Medicine, Kangnam St Mary's Hospital, 505 Banpo-Dong, Seocho-Gu, Seoul, Korea.
Yonsei Med J. 2007 Apr 30;48(2):308-16. doi: 10.3349/ymj.2007.48.2.308.
We recently reported that rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, has a protective effect against cyclosporine (CsA)- induced renal injury. Here we report the effect of RGTZ on peroxisome proliferator-activated receptor gamma (PPARgamma) expression in an experimental model of chronic cyclosporine (CsA) nephropathy.
Chronic CsA nephropathy was induced in Sprague-Dawley rats by administering CsA (15mg/kg per day) for 28 days, and control rats were treated with vehicle (VH group, olive oil 1mL/kg per day) for 28 days. RGTZ (3mg/kg) was concurrently administered via gavage to the CsA and VH groups. Expression of PPARgamma mRNA and protein was evaluated with RT-PCR, immunohistochemistry, and immunoblotting.
PPARgamma mRNA expression was similar to the level of PPARgamma protein constitutively expressed in the kidneys of the VH treated rats, with expression in the glomerular epithelial, distal tubular cells, and collecting tubular cells. PPARgamma protein expression in CsA-treated rat kidneys was significantly less than in the VH group. However, concomitant administration of RGTZ restored PPARgamma protein expression in the kidneys of the CsA- reated rats.
Exogenous administration of RGTZ treatment upregulates PPARgamma expression and that this mechanism may play a role in protecting against CsA-induced renal injury.
我们最近报道，罗格列酮（RGTZ），一种过氧化物酶体增殖物激活受体γ（PPARγ）激动剂，对环孢素（CsA）诱导的肾损伤具有保护作用。在此，我们报告RGTZ对慢性环孢素（CsA）肾病实验模型中过氧化物酶体增殖物激活受体γ（PPARγ）表达的影响。
通过给予CsA（每天15mg/kg）28天，在Sprague-Dawley大鼠中诱导慢性CsA肾病，对照大鼠用赋形剂处理（VH组，每天1mL/kg橄榄油）28天。RGTZ（3mg/kg）通过灌胃同时给予CsA组和VH组。用RT-PCR、免疫组织化学和免疫印迹法评估PPARγ mRNA和蛋白的表达。
PPARγ mRNA表达与VH处理大鼠肾脏中组成性表达的PPARγ蛋白水平相似，在肾小球上皮细胞、远曲小管细胞和集合小管细胞中均有表达。CsA处理的大鼠肾脏中PPARγ蛋白表达明显低于VH组。然而，同时给予RGTZ可恢复CsA处理大鼠肾脏中PPARγ蛋白的表达。
外源性给予RGTZ治疗可上调PPARγ表达，且该机制可能在预防CsA诱导的肾损伤中起作用。
