This research aims to observe and compare the wound healing process of urethral bladder after transurethral
holmium laser resection of
bladder tumor (HoLRBT) and
transurethral resection of bladder tumor (TURBT) and explore the possible mechanism of wound healing and bladder re-epithelialization after HoLRBT. An animal model of canine achieving HoLRBT and TURBT was established. Cystoscopy was performed at different time points (3 days and 1, 2, 3, and 4 weeks) after operation to observe the wound healing and re-epithelialization of bladder epithelium. Bladder mucosa specimens were obtained and histopathological changes of the bladder epithelium were observed under light microscope after HE staining. Immunochemistry was used to determine the cell expression ofCK5, CK14,
EGF, EGFR;
microRNA expressions of CK5, CK14,
EGF, and EGFR were measured by qRT-PCR. The changes of urinary
EGF concentration were detected by ELISA. The bladder epithelial
wound was repaired and re-epithelialized at 1 week after HoLRBT. At the 4th week, the bladder
wound was basically completed and re-epithelialized; repair of bladder epithelial
wounds recapitulates the
wounds with the proliferation and migration of residual epithelial cells under the
wound and the bladder epithelium that proliferates alongside the
wound surface to complete re-epithelialization. The process begins at 1 week after surgery and basically completes at 4 weeks after surgery. CK5 and CK14 positive cells were detected in the basal cells of the bladder epithelium after HoLRBT, and the expression of CK5 and CK14
mRNA in the basal cells of the bladder epithelium under
hyperplasia was significantly higher than that of the normal bladder epithelial basal cells. Bladder epithelial
wound repair of TURBT group was performed by the proliferative differentiation of the peri-bladder epithelium adjacent to the
wound edge and crawled to the
wound surface to complete the re-epithelialization process. The
wound repair and re-epithelialization were significantly slower than HoLRBT group. The CK5 and CK14 positive cells can also be detected in the basal cells of marginal
hyperplasia of basal margin, and the expression of CK5 and CK14
mRNA in the basal cells of the peri-bladder
hyperplasia is obviously higher than that of the normal bladder epithelial basal cells. The expression of
EGF in bladder regenerating epithelium gradually increased with time after HoLRBT. Bladder basal cells and bladder regenerating epithelium express high levels of EGFR after HoLRBT. The concentration of
EGF in urine after HoLRBT and TURBT increased significantly after surgery, and peaked at 3 days after operation. The urinary
EGF concentration in HoLRBT group was higher than that in TURBT group at 3 and 4 weeks after operation. The re-epithelialization process can be seen 1 week after the
cystectomy with
holmium laser cystectomy, and the epithelialization rate is faster than the traditional transection surgery. This is because the residual bladder epithelial stem cells and
wound marginal epithelial cells are involved in the process of
wound repair and re-epithelialization following HoLRBT. But only the marginal epithelial tissue participates in the re-epithelialization process after TURBT, so the repair rate of TURBT is slower. The repair of bladder epithelium after HoLRBT is related to the stimulation of
tissue factor EGF. The regenerated bladder epithelium also participates in the
wound repair process by means of autocrine of
EGF.