[Protective effects of metanephric mesenchymal cells on acute renal tubular damage: experiment with rats].
OBJECTIVE
To study the protective effects of metanephric mesenchymal cells (MMCs) on acute renal tubular damage and explore its possible mechanism.


METHODS
MMCs were isolated and cultured from 13-day-old embryonic rats and labeled with 5-bromodeoxyuridine. Seventy-two male SD rats were randomly divided into 3 equal groups: MMC group, receiving MMC injection instantaneously when ischemia/reperfusion (I/R) renal injury was induced, I/R group, undergoing I/R to establish acute renal tubular damage models, and sham operation group. Six rats from each group were killed at different time points: 24 h, 48 h, 72 h, and 96 h later. Blood sample was collected from the vena cava inferior, to examine the serum creatinine (SCr) and blood urea nitrogen (BUN). Specimens of kidney underwent microscopy. Apoptosis was conformed by TUNEL assay. Immunohistochemistry was used to detect the protein expression of Bcl-2 and Bax. The distribution of MMCs labeled with 5-bromodeoxyuridine in kidney was observed by immunofluorescence technique.


RESULTS
The SCr and BUN levels in different time points of the MMC group were both significantly lower than those of the I/R group (both P <0.05), HE staining showed that pathological damage of the MMC group was less than that of the I/R group (P <0.05). TUNEL results investigated that the number of apoptosis renal tubular epithelial cells of the MMC group was (13.4 +/- 3.2/HPF), significantly less than that of the I/R group [(25.4 +/- 5.2/HPF)]. In comparison with the I/R group, there were more Bcl-2 positive cells and fewer Bax positive cells in the MMC group. BrdU-labeled MMCs began to occur in the renal tissue (60 +/- 6/HP) In the 72 h subgroup of MMC group, and number of BrdU-labeled MMCs, the 96 h subgroup was (143 +/- 8/HP), significantly higher than that of the 72 h subgroup (P<0.05).


CONCLUSIONS
MMCs have the ability to protect renal function in acute renal tubular damage in rats, migrate and repopulate in the I/R injured renal tubules, and inhibits renal tubular epithelial cell apoptosis. The mechanism may be involved in regulating the expression of Bcl-2 and Bax.
Zhou
Jian-feng
JF
Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. zhoujf1978@yahoo.com.cn
Yuan
Fa-Huan
FH
Li
Na
N
Yu
Jun
J
Zhang
Yao-Quan
YQ
Hou
Wei-Ping
WP
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D001806:Blood Urea Nitrogen; D017690:Cell Transplantation / Q000379:methods; D003404:Creatinine / Q000097:blood; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology / Q000601:surgery*; D007684:Kidney Tubules / Q000098:blood supply / Q000473:pathology / Q000601:surgery*; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D051028:bcl-2-Associated X Protein; D003404:Creatinine