Ultrasound-mediated microbubble destruction increases renal interstitial capillary permeability in early diabetic nephropathy rats.
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.
['Zhang|Yi|Y|', 'Ye|Chuan|C|', 'Xu|Yali|Y|', 'Dong|Xuexin|X|', 'Li|Jianping|J|', 'Liu|Rong|R|', 'Gao|Yunhua|Y|']
D000818:Animals D015153:Blotting, Western D002199:Capillary Permeability D003921:Diabetes Mellitus, Experimental D003928:Diabetic Nephropathies D005070:Evans Blue 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
Microbubble Capillary permeability Diabetic nephropathy Ultrasound