Combined Microencapsulated Islet Transplantation and Revascularization of Aortorenal Bypass in a Diabetic Nephropathy Rat Model

Abstract

Objective. Revascularization of aortorenal bypass is a preferred technique for renal artery stenosis (RAS) in diabetic nephropathy (DN) patients. Restenosis of graft vessels also should be considered in patients lacking good control of blood glucose. In this study, we explored a combined strategy to prevent the recurrence of RAS in the DN rat model. Methods. A model of DN was established by intraperitoneal injection of streptozotocin. Rats were divided into 4 groups: SR group, MIT group, Com group, and the untreated group. The levels of blood glucose and urine protein were measured, and changes in renal pathology were observed. The expression of monocyte chemoattractant protein-1 (MCP-1) in graft vessels was assessed by immunohistochemical staining. Histopathological staining was performed to assess the pathological changes of glomeruli and tubules. Results. The levels of urine protein and the expression of MCP-1 in graft vessels were decreased after islet transplantation. The injury of glomerular basement membrane and podocytes was significantly ameliorated. Conclusions. The combined strategy of revascularization and microencapsulated islet transplantation had multiple protective effects on diabetic nephropathy, including preventing atherosclerosis in the graft vessels and alleviating injury to the glomerular filtration barrier. This combined strategy may be helpful for DN patients with RAS.

Combination CTLA-4 immunoglobulin treatment and ultrasound microbubble-mediated exposure improve renal function in a rat model of diabetic nephropathy

“…In total we utilized 75 rats that were randomized into 5 groups (n=15/group): Control rats that were fed regular food and water without treatment (Group A); an untreated model group in which DN was established based on prior approaches [ 63 ], with rats being maintained on a high-far high-sugar diet for 8 additional weeks without any treatment (Group B); a CTLA-4-Ig group in which DN was established as above, and rats were fed a high-fat high-sugar diet for 8 weeks during which time they were intravenously administered 0.5 mg/kg CTLA-4-Ig per week via tail vein injection (Group C); A microbubble exposure group in which DN was established as above, rats were maintained on a high-fat high-sugar diet for 8 weeks during which they SonoVue tail vein injections (1 ml/kg/week) with simultaneous ultrasound exposure to the kidneys (Group D); A combination CTLA-4-Ig + ultrasound microbubble exposition group wherein rats were treated as in Group D, but were injected with both CTLA-4-Ig (0.5 mg/kg/w) and SonoVue (1 ml/kg/w) while undergoing ultrasound exposure (Group E). The rats’ kidneys were exposed to 1 MHz ultrasound waves for 4 minutes per exposure twice per week with the following settings: 100 Hz pulse repetition frequency, 1.5 W/cm 2 output intensity, 0.2 MPa peak negative acoustic pressure and 60% duty cycle [ 64 ].…”