Evaluation of the protective effects of matrix metalloproteinases inhibitor on testicular ischemia-reperfusion injury by contrast-enhanced ultrasound

Objective To explore novel lipid microbubbles with matrix metalloproteinase-9(TMB-9) targeting in the radiography evaluation of the protective effects of doxycycline on testicular ischemia-reperfusion injury by contrast-enhanced ultrasound(CEUS). Methods Thirty-six rabbits were randomly divided into control groups (group S1 and group S2), ischemia reperfusion groups (group R1 and group R2) and doxy intervention groups (group D1 and group D2). In the control groups, threading without ligation was performed after the exposure of the spermatic cord. The establishment of ischemia-reperfusion model was performed in ischemia reperfusion groups and doxy intervention groups, followed by 1-day feeding for group R1 and D1 as well as 4-day feeding for group R2 and D2.Group D1, group D2 and group S1 were given intraperitoneal injection of doxy 20 mg·kg-1·d-1. Group R1, group R2 and group S2 were given intraperitoneal injection of equivalent normal saline. MB and TMB-9 CEUS were undertook preoperative and postoperative respectively in each group.And the changes of the contrast parameters were analyzed, including PI, TP, Slope, MTT, DT/2 and AUC.The testes were taken for pathological examination after operation. Results TMB-9 contrast parameters of the group D1 including PI and AUC were significantly decreased, MTT and DT/2 decreased(P<0.05), compared with Group R1.While compared with MB, TMB-9 contrast parameters of group D1 including PI and AUC were increased, MTT and DT/2 prolonged (P<0.05). TMB-9 contrast parameters of Group D2 including PI and AUC were significantly decreased, MTT and DT/2 decreased(P<0.01), compared with Group R2.TMB-9 contrast parameters of Group D2 only PI increased (P<0.01), while compared with MB.Compared with the ischemia reperfusion group, the expression of MMP-9 in the vascular basement membrane of doxy intervention groups was significantly decreased (P<0.01). Conclusions TMB-9 can sensitively and objectively evaluate testicular ischemia-reperfusion injury of testicular microvasculature at different reperfusion times before and after doxy intervention. Key words: Contrast-enhanced ultrasound; Reperfusion injury; Testicular; MMP-9; Doxycycline