Analysis of apoptosis and cell proliferation after high intensity-focused ultrasound ablation combined with microbubbles in rabbit livers.
OBJECTIVE
To analyze apoptosis and expression of proliferating cell nuclear antigen (PCNA) sequentially in the rabbit liver tissue after high-intensity focused ultrasound (HIFU) ablation combined with microbubbles.


METHODS
Fifty rabbits were divided into two groups randomly. Rabbits in group I received injections with ultrasound contrast agent Sonovue, before HIFU ablation, on their livers and those in group II were ablated by a single HIFU exposure without microbubbles. Rabbits were killed on days 0, 1, 3, 7 and 14 after HIFU ablation. The livers were excised for light microscopic examination with hematoxylin and eosin staining, immunohistochemical staining for PCNA expression and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling (TUNEL) staining for apoptosis.


RESULTS
A fibra tissue band composed of fibrocytes and capillary vessels, which was detected by light microscope in the rim of the targeted area after 3 days in group I, was wider than that in group II. The apoptosis index (the number of apoptotic events divided by the total cell number in the same field) and PCNA-positive index (the number of PCNA-positive cells divided by the total cell number in the same field) in group I on days 0, 1, 3, 7 and14 after HIFU ablation were higher than those in group II.


CONCLUSIONS
Microbubbles can improve the apoptosis and cell proliferation in zones surrounding coagulated necrosis areas after HIFU ablation, which may be explored to benefit enhanced HIFU treatment.
Department of Ultrasound in Xijing Hospital, Fourth Military Medical University, 17th Changle Xilu, Xi'an, China.
Wen
W
Luo
Xiaodong
X
Zhou
Jun
J
Zhang
Yunqiu
Y
Qian
Minjuan
M
Zheng
Ming
M
Yu
Xiaoyin
X
Gong
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D049109:Cell Proliferation; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy; D045423:Microbubbles; D023421:Models, Animal; D010743:Phospholipids / Q000008:administration & dosage*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011817:Rabbits; D011897:Random Allocation; D013459:Sulfur Hexafluoride / Q000008:administration & dosage*; D014464:Ultrasonic Therapy / Q000379:methods*; D014463:Ultrasonography
D015415:Biomarkers; D010743:Phospholipids; D018809:Proliferating Cell Nuclear Antigen; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride