[Changes of tight junction and Cx43 expression in microvessel endothelial cells of mouse lung induced by bleomycin].
OBJECTIVE
To investigate the changes of expression of connexin-43 (Cx43) and the tight junction of microvessel endothelial cells (EC) to approach the effects in bleomycin (BLM) induced pulmonary fibrosis (PF).


METHODS
Forty healthy rats were equally and randomizedly divided into the control group and the experiment group. In both group, vWf in blood serum was measured with ELISA method on 3rd, 7th, 14th, 28th day after BLM treatment. Rats in each group were infused with lanthanum nitrate on 3rd, 7th, 14th, 28th day after BLM treatment. The lung samples were made and the tight junction and the distribution of the granules of lanthanum in the microvessel EC were observed with transmission electron microscopy in the control and experiment groups. The lung microvessel EC of the rats in each group were preserved by tissue culture methods at the same time, and the expression of Cx43 were observed by laser scanning confocal microscopy.


RESULTS
The serum vWf in the peripheral blood of the experiment group was significantly higher than that of the control group, and was the highest on 3rd day after BLM treatment (P < 0.01). The blood vessel EC of the control group were intact. The basement membrane was uninterrupted. Granules of lanthanum nitrate did not penetrate the tight junction of EC. The width of junction gap in the experimental group was increased and the lanthanum granules of high density were found deposited in the linear form in the gap junction. Low expression of Cx43 was observed in experiment group. The expression rate of Cx43 was 25%, 38%, 45% and 71% respectively on 3rd, 7th, 14th, 28th day, significantly less than those in the control group (P < 0.05).


CONCLUSIONS
It may be the important pathological basis for the BLM induced abnormality of the interstitial tissues in the lung that the tight junction of EC is continuously in the open state, which causes the effusions of inflammatory cells and the corresponding cytokine secretion, and thus initiates the overproliferation of fibroblasts.
Cui
Guang-bin
GB
Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Wei
Jing-guo
JG
Wang
Wei
W
Yin
Qian
Q
Wang
Chun-mei
CM
Wei
Long-xiao
LX
Yang
Hao
H
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D018031:Connexin 43 / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008168:Lung / Q000098:blood supply; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000187:drug effects*
D018031:Connexin 43; D001761:Bleomycin