Liu Bin, Chen Ming, Peng Hong-xia, Zhang Chao, Ou San-tao
Department of Nephrology, the Affiliated Hospital of Luzhou Medical College, Luzhou 646000, Sichuan, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007 Dec;19(12):739-41.
To observe the expression of peroxisome proliferation activated receptor gamma (PPAR gamma) at different periods in renal interstitium and to study the effect of atorvastatin on the protein expression of PPAR gamma in unilateral ureteral obstruction (UUO) in a rat model.
Forty-five female Sprague-Dawley (SD) rats were divided into three groups: the sham operation group, the model group and the atorvastatin group. The latter two groups underwent UUO and then received vehicle only or atorvastatin (10 mg.kg(-1).d(-1)) by daily gastric gavage, from three days before the UUO operation to the day of sacrifice . The sham operation rats received vehicle. Five rats of each group were sacrificed respectively at 5, 10 and 15 days after surgery. Histological changes in renal tissue were observed by hematoxylin and eosin (HE) and Masson stain. Immunohistochemistry for PPAR gamma was performed in renal interstitium at each time point.
Interstitial expansion and fibrosis in ureter obstructed kidney was prominent in the model group. Atorvastatin seemed to have ameliorated interstitial expansion and fibrosis in atorvastatin group. Detectable basic PPAR gamma expression was observed in renal inner medulla of rats in sham operation group, and it was mainly concentrated in collecting tubules. In UUO rats, PPAR gamma expression was found increased and extended to renal tubular epithelial cells. Increased PPAR gamma expression was found on the 5th day after UUO, and significant PPAR gamma expression was found on the 10 th day after UUO. The increased PPAR gamma expression was found to be downregulated on the 15 th day after UUO, but still significantly increased compared with that of the model group at the same time point (all P<0.01). Atorvastatin could significantly increase the expression of PPAR gamma as compared with the model group at each time point (all P<0.01).
PPAR gamma expression was found increased, and it appeared in renal tubular epithelial cells in UUO rats, Atorvastatin may play a protective role in the kidney by activating PPAR gamma, thus alleviating renal interstitial fibrosis following UUO in rats.
观察过氧化物酶体增殖物激活受体γ（PPARγ）在肾间质不同时期的表达情况，并研究阿托伐他汀对单侧输尿管梗阻（UUO）大鼠模型中PPARγ蛋白表达的影响。
45只雌性Sprague-Dawley（SD）大鼠分为三组：假手术组、模型组和阿托伐他汀组。后两组进行UUO手术，然后从UUO手术前3天至处死当天，仅给予溶剂或通过每日灌胃给予阿托伐他汀（10 mg·kg⁻¹·d⁻¹）。假手术大鼠给予溶剂。每组分别在术后5、10和15天处死5只大鼠。用苏木精-伊红（HE）和Masson染色观察肾组织的组织学变化。在每个时间点对肾间质进行PPARγ免疫组织化学检测。
模型组输尿管梗阻肾间质扩张和纤维化明显。阿托伐他汀似乎改善了阿托伐他汀组的间质扩张和纤维化。在假手术组大鼠的肾内髓质中观察到可检测到的基础PPARγ表达，且主要集中在集合小管。在UUO大鼠中，发现PPARγ表达增加并扩展至肾小管上皮细胞。UUO术后第5天发现PPARγ表达增加，UUO术后第10天发现PPARγ表达显著增加。发现UUO术后第15天PPARγ表达增加下调，但与同一时间点的模型组相比仍显著增加（均P<0.01）。与模型组相比，阿托伐他汀在每个时间点均可显著增加PPARγ的表达（均P<0.01）。
在UUO大鼠中发现PPARγ表达增加，且出现在肾小管上皮细胞中，阿托伐他汀可能通过激活PPARγ对肾脏发挥保护作用，从而减轻大鼠UUO后的肾间质纤维化。
