摘要
目的观察吡格列酮对糖尿病大鼠肾组织骨桥蛋白表达的影响。方法 SD大鼠随机分为正常对照组和造模组。链脲佐菌素诱导糖尿病大鼠。造模成功的大鼠随机分为糖尿病组、吡格列酮3,15 mg·kg-1·d-1组。8周末测大鼠24 h尿微量白蛋白、血糖,血肌酐。HE染色观察肾组织形态,免疫组织化学法及逆转录-聚合酶链反应法分别测大鼠肾组织骨桥蛋白及骨桥蛋白mRNA的表达。结果吡格列酮3 mg·kg-1·d-1组、吡格列酮15 mg·kg-1·d-1组血肌酐、微量白蛋白、肾质量/体质量较糖尿病组明显下降(P<0.05)。与糖尿病组比较,吡格列酮15 mg·kg-1·d-1组血糖明显降低(P<0.05),吡格列酮3mg·kg-1·d-1组血糖无明显改善,差异无统计学意义(P>0.05)。糖尿病组肾组织骨桥蛋白及骨桥蛋白mRNA表达水平较正常对照组明显升高(P<0.05)。吡格列酮3,15 mg·kg-1·d-1组肾组织骨桥蛋白、骨桥蛋白mRNA表达水平较糖尿病组均明显下降(P<0.05)。结论糖尿病大鼠肾组织骨桥蛋白表达增加,提示骨桥蛋白可能参与糖尿病肾脏病变的发病过程。吡格列酮干预可以减少糖尿病大鼠尿微量白蛋白,对肾脏有保护作用。吡格列酮对肾脏的保护作用部分可能与吡格列酮抑制肾脏骨桥蛋白的表达有关。
OBJECTIVE To investigate the effect of pioglitazone on renal osteopontin expression in diabetic rats. METHODS Sprague Dawlry rats were randomly divided into the normal control group and the model group. Diabetes was induced by streptozotoein （STZ） in the model group rats. After diabetes was confirmed, diabetic rats were assigned randomly into three subgroups ： the diabetic rats without treatment, 3 and 15 mg·k^-1·d^-1 pioglitazone treated diabetic rats. At the end of the 8^th week, 24 h urine samples were collected to examine mieroalbuminuria （mAlb）. At the same time, blood glucose levels and serum creatinine （Ser） were measured. Stained kidney sections were observed under light microscope. The expressions of OPN protein and OPN mRNA were detected by immuuohistochemistry and reverse transcription-polymerase chain reaction（RT-PCR） , respectively. RESULTS Treatment with 3 and 15 mg ·k^-1·d^-1 pioglitazone could decrease Scr, mAlb and RKW in diabetic rats. Compared with diabetic rats, blood glucose level was lower in diabetic rats treated with 15 mg ·k^-1·d^-1 pioglitazone; however, no significant change was observed at the 3 mg ·k^-1·d^-1dose. Compared with normal control rats, the OPN protein and mRNA expressions of the whole nephritic kidney in diabetic rats were upregulated （P 〈 0. 05 ）. After treatment with 3 and 15 mg ·k^-1·d^-1 pioglitazone, the expressions of OPN protein and mRNA reduced compared with diabetic rats （P 〈 0.05）. CONCLUSION The OPN expression in renal tissues is increased in diabetic rats, suggesting that OPN has emerged as a potential key pathophysiologic contributor in diabetic nephropathy （ DN）. Pioglitazone can reduce microalbuminuria in diabetic rats. The renal protective effect of pioglitazone in DN may involve the suppression of increased OPN.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2013年第6期441-445,共5页
Chinese Pharmaceutical Journal
关键词
吡格列酮
糖尿病肾病
骨桥蛋白
炎症
pioglitazone
diabetic nephropathy
osteopontin
inflammation
