title: Ultrasound-mediated microbubble destruction increases renal interstitial capillary permeability in early diabetic nephropathy rats.
abstract: Diabetic nephropathy (DN) is defined as persistent proteinuria corresponding to a urinary albumin excretion rate >300 μg/mg in the absence of other non-diabetic renal diseases. The aim of this study was to determine if ultrasound (US)-mediated microbubble (MB) destruction could increase renal interstitial capillary permeability in early DN rats. Diabetes was induced with streptozotocin. DN rats presented with mild micro-albuminuria 30 d after onset of diabetes. DN rats (N = 120) were divided into four groups that received Evans blue (EB) followed by: (i) no treatment (control group); (ii) continuous ultrasonic irradiation for 5 min (frequency = 7.00 MHz, mechanical index = 0.9, peak rarefactional pressure = 2.38 MPa: US group); (iii) microbubble injection (0.05 mL/kg: MB group); and (iv) both ultrasound and microbubble injection (US + MB group). Another 8 DN rats were subjected to ultrasound and microbubbles and then injected with EB after 24 h (recovery group). EB content, EB extravasation and E-selectin mRNA and protein expression significantly increased, and interstitial capillary walls became discontinuous in the US + MB group. Neither hemorrhage nor necrosis was observed on renal histology. Urine samples were collected 24 h post-treatment. There was no hematuria, and the urinary albumin excretion rate did not increase after ultrasound-microbubble interaction detected by urinalysis. EB content returned to the control group level after 24 h, as assessed for the recovery group. In conclusion, ultrasound-mediated microbubble destruction locally increased renal interstitial capillary permeability in DN rats, and should be considered a therapy for enhancing drug and gene delivery to the kidney in the future.
authors.affiliation: Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, Chongqing, China; Department of Ultrasound, Forty-Fourth Military Hospital, Guiyang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Guiyang Medical College, Guiyang, China; Center for Tissue Engineering and Stem Cells, Guiyang Medical College, Guiyang, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Ye
authors.affiliation: Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, Chongqing, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Ultrasound, Forty-Fourth Military Hospital, Guiyang, China.
authors.forename: Xuexin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Ultrasound, Forty-Fourth Military Hospital, Guiyang, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Forty-Fourth Military Hospital, Guiyang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, Chongqing, China. Electronic address: gyh755631@163.com.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000000981:diagnostic imaging / Q000628:therapy*; D005070:Evans Blue / Q000494:pharmacology; D008297:Male; D045423:Microbubbles; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014464:Ultrasonic Therapy; D014463:Ultrasonography; D016482:Urinalysis
chemical_list: D005070:Evans Blue
keywords: Capillary permeability; Diabetic nephropathy; Microbubble; Ultrasound