The therapeutic effects of bosentan and valsartan on renal interstitial fibrosis of chronic aristolochic acid nephropathy

	The therapeutic effects of bosentan and valsartan on renal interstitial fibrosis of chronic aristolochic acid nephropathy
	ZHANG Cong; CHEN Yipu; DONG Hongrui; QIU Changbin
刊名	National Medical Journal of China
	2005
卷号	85 期号:37 页码:2601-2606
关键词	Aristolochic acid Angiotensin Ⅱ Endothelin-1 Nephritis interstitial
ISSN号	0376-2491
其他题名	波生坦及缬沙坦对马兜铃酸肾病大鼠肾间质纤维化的影响
文献子类	Article
英文摘要	Objective To investigate the therapeutic effects of endothelin receptor antogonist （bosentan） and angiotensin Ⅱ type 1 receptor antagonist （valsartan） on renal interstitial fibrosis of rats with chronic aristolochic acid nephropathy （CAAN）. Methods A rat model of CAAN was established by gavage with extract of Aristolochia manshuriensis Kom intermittently, and then they were divided into the following three groups, i.e. model group, bosentan group （ 100 mg· kg^-1· d^-1 by gavage） and valsartan group （30 mg · kg^-1· d^-1 by gavage）. Control group （CTR） only received tap water by gavage. Each group consisted of 6 rats. At the end of 1st, 4 th, 8 th, 12 th and 16 th week, urinary protein excretion, urinary beta2 microglobumin （beta2-mG） and serum creatinine （SCr） were measured. Afterwards the rats were sacrificed. The relative area of renal interstitial fibrosis on pathological section was semi-quantitatively determined. The mRNA and the protein expression of transforming growth factor-beta1 （ TGF-beta1 ） , connective tissue growth factor （CTGF）, plasminogen activator inhibitor-1 （PAI-1）, tissue inhibitor of metalloproteinase-1 （TIMP-1） and collagen Ⅰ （Col Ⅰ ） in kidney tissue was semi-quantitatively determined with reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemical staining, respectively. Results Compared with CTR, urinary protein excretion, urinary beta2-mG and Scr were significantly increased （ P 〈 0. 05 or 0.01 ） and relative area of interstitial fibrosis was also significantly enlarged in the model group （3. 964 0. 739% ,CTR 0. 158 0. 059% ,P 〈0. 01 ）. Compared with CTR, the expression of TGF-beta1, CTGF, PAI-1, TIMP-1 and Col Ⅰ mRNA and protein was significantly upregulated in the model group （ P 〈 0.01 ）. After intervention with bosentan or valsartan the up-regulating abovementioned parameters were all significantly inhibited （ P 〈 0. 05 or 0. 01 ）. However, there was no difference between bosentan group and valsartan group. Conclusion Bosentan and valsartan both can ameliorate renal interstitial fibrosis and improve renal function in rats with CAAN. These responses may result from the inhibition effects on the promoting factors of ECM synthesis （TGF-beta1, CTGF）and the antagonistic factors of ECM degradation（ PAI-1 ,TIMP-1 ）.
资助项目	国家自然科学基金资助项目[00000000] ; 卫生部部属（管）医疗机构临床学科重点项目[00000000]
WOS研究方向	Surgery (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:2148643
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/268284]
专题	中国科学院上海药物研究所
作者单位	Center of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China.
推荐引用方式 GB/T 7714	ZHANG Cong,CHEN Yipu,DONG Hongrui,et al. The therapeutic effects of bosentan and valsartan on renal interstitial fibrosis of chronic aristolochic acid nephropathy[J]. National Medical Journal of China,2005,85(37):2601-2606.
APA	ZHANG Cong,CHEN Yipu,DONG Hongrui,&QIU Changbin.(2005).The therapeutic effects of bosentan and valsartan on renal interstitial fibrosis of chronic aristolochic acid nephropathy.National Medical Journal of China,85(37),2601-2606.
MLA	ZHANG Cong,et al."The therapeutic effects of bosentan and valsartan on renal interstitial fibrosis of chronic aristolochic acid nephropathy".National Medical Journal of China 85.37(2005):2601-2606.