机构:[1]Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China,中山大学附属第一医院[2]Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, Guangdong, China[3]Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China深圳市康宁医院深圳医学信息中心
The proximal tubular epithelial cells (PTECs) are the primary target of aristolochic acids and especially vulnerable to mitochondrial injury from insults of toxic xenobiotics.
This study aimed to investigate the possible role of mitochondrial injury in Caulis Aristolochia manshuriensis (CAM)-induced aristolochic acid nephropathy (AAN).
Male Sprague-Dawley rats were gavaged with CAM extract every other week for 1, 4, 8 and 12 weeks, respectively.
The rats in the model group showed chronic AAN as evidenced by worsening kidney function evaluated by blood urea nitrogen, creatinine and proteinuria levels, and severe tubulointerstitial injury marked by massive tubular atrophy and interstitial fibrosis in kidney tissues. Moreover, overt apoptosis and impaired regeneration of PTECs were observed in AAN rats. Furthermore, the study revealed that mitochondria in PTECs were fragmented into small, punctuate suborganelles in AAN rats. Two mitochondrial respiratory chain proteins, mitochondrial DNA (mtDNA)-encoded cytochrome c oxidase subunit І (COX-І) and nuclear DNA-encoded nicotinamide adenine dinucleotide dehydrogenase (ubiquinone)-1β subcomplex 8 (NDUFβ8), were both down-regulated after one week of CAM treatment. However, with AAN progression, NDUFβ8 level restored, while COX-І level maintained low. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), master regulator of mitochondrial biogenesis, was significantly down-regulated at week 4 and week 8, but significantly up-regulated at week 12. In addition, mtDNA copy number reduced markedly along with AAN progression.
A rat model of chronic AAN was successfully reproduced by gavage with CAM extract. Dynamic changes of mitochondrial injury induced by CAM might contribute to the AAN progression.
基金:
This research was supported by the Natural Science
Foundation of China (Grant No. 81073138 and 81570614),
the National Basic Research Program of China (Grant No.
2012CB517700–2012CB517706), the National Science Fund
for Distinguished Young Scholars of China (Grant No.
30925019), Key Project of Chinese National Programs for
Fundamental Research and Development (973 Program)
(Grant No. 2012CB517701) and Guangdong Natural
Science Foundation of China (Grant No 2014A030313139
and 2015A030310252).
第一作者机构:[1]Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China,[2]Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, Guangdong, China[3]Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
共同第一作者:
通讯作者:
通讯机构:[1]Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China,[2]Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, Guangdong, China[*1]Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
推荐引用方式(GB/T 7714):
Xinhui Liu,Juan Wu,Juan Wang,et al.Possible role of mitochondrial injury in Caulis Aristolochia manshuriensis-induced chronic aristolochic acid nephropathy.[J].DRUG AND CHEMICAL TOXICOLOGY.2017,40(1):115-124.doi:10.1080/01480545.2016.1188303.
APA:
Xinhui Liu,Juan Wu,Juan Wang,Jinjin Fan,Xiaoran Feng...&Xiao Yang.(2017).Possible role of mitochondrial injury in Caulis Aristolochia manshuriensis-induced chronic aristolochic acid nephropathy..DRUG AND CHEMICAL TOXICOLOGY,40,(1)
MLA:
Xinhui Liu,et al."Possible role of mitochondrial injury in Caulis Aristolochia manshuriensis-induced chronic aristolochic acid nephropathy.".DRUG AND CHEMICAL TOXICOLOGY 40..1(2017):115-124