动物造模,药效评价,肾动脉狭窄高血压 z-bio 2024-07-18 431

　　In addition to the DOCA hypertensive miniature pig model, experimental renal artery stenosis can also lead to the formation of renal hypertension. Renal artery stenosis promotes microvascular thinning and fibrosis, ultimately leading to irreversible kidney injury. Previous studies by Ebrahimi et al. have found that percutaneous renal angioplasty or endothelial progenitor cells can improve renal cortical hemodynamics and renal function after stenosis. The renal medulla is particularly sensitive to hypoxia, although little is currently known about whether the recovery of renal blood flow after medullary injury is reversible. This study aims to verify that percutaneous renal angioplasty, with or without the delivery of endothelial progenitor cells from narrowed kidneys, may enhance medullary remodeling and tubular function. The experiment induced renal artery stenosis by implanting stimulating coils in 21 miniature pigs, while using normal controls. Two groups with renal artery stenosis underwent percutaneous renal angioplasty or percutaneous renal angioplasty combined with endothelial progenitor cells after 6 weeks. After 4 weeks, the medullary hemodynamics, microvascular structure, and oxygen dependent tubular function of the narrowed kidney were detected by multi-slice computed tomography, microscopic computer-assisted tomography, and oxygen dependent MRI, respectively. The results showed that the medullary vascular density and blood flow were reduced in all renal artery stenosis groups. However, in small pigs with renal artery stenosis treated with percutaneous renal angioplasty combined with endothelial progenitor cells, endothelial progenitor cells were implanted into the tubular structure, and standardized oxygen dependent tubular function was reduced by fibrosis. This suggests that percutaneous angioplasty combined with endothelial progenitor cell input can restore medullary oxygen dependent tubular function, despite impaired medullary blood flow and oxygen supply. This result provides a basis for adjuvant cell therapy for future renal artery stenosis angiogenesis surgery.

　　Urbieta Caceres et al. found that reversing experimental renal vascular hypertension can restore coronary microvascular function and structure. Hypertension leads to left ventricular hypertrophy and vascular disorders, and causes poor prognosis in cardiovascular disease. In the study, the use of percutaneous renal angioplasty to lower blood pressure can improve the function and structure of coronary microvessels, alleviate inflammation and fibrosis. The experiment induced the establishment of a small pig model of renal vascular hypertension by placing locally stimulated coils in the renal artery. After percutaneous endovascular renal angioplasty treatment, blood pressure and left ventricular hypertrophy were significantly reduced, microvascular permeability and response to adenosine were improved. Reversing early renal vascular hypertension can improve coronary microvascular function and structure, reverse myocardial hypertrophy and diastolic dysfunction, reduce myocardial ischemia and inflammation, suggesting that adjusting blood pressure to normal can protect cardiovascular function and structure.

　　In addition to the DOCA hypertensive miniature pig model, experimental renal artery stenosis can also lead to the formation of renal hypertension. Renal artery stenosis promotes microvascular thinning and fibrosis, ultimately leading to irreversible kidney injury. Previous studies by Ebrahimi et al. have found that percutaneous renal angioplasty or endothelial progenitor cells can improve renal cortical hemodynamics and renal function after stenosis. The renal medulla is particularly sensitive to hypoxia, although little is currently known about whether the recovery of renal blood flow after medullary injury is reversible. This study aims to verify that percutaneous renal angioplasty, with or without the delivery of endothelial progenitor cells from narrowed kidneys, may enhance medullary remodeling and tubular function. The experiment induced renal artery stenosis by implanting stimulating coils in 21 miniature pigs, while using normal controls. Two groups with renal artery stenosis underwent percutaneous renal angioplasty or percutaneous renal angioplasty combined with endothelial progenitor cells after 6 weeks. After 4 weeks, the medullary hemodynamics, microvascular structure, and oxygen dependent tubular function of the narrowed kidney were detected by multi-slice computed tomography, microscopic computer-assisted tomography, and oxygen dependent MRI, respectively. The results showed that the medullary vascular density and blood flow were reduced in all renal artery stenosis groups. However, in small pigs with renal artery stenosis treated with percutaneous renal angioplasty combined with endothelial progenitor cells, endothelial progenitor cells were implanted into the tubular structure, and standardized oxygen dependent tubular function was reduced by fibrosis. This suggests that percutaneous angioplasty combined with endothelial progenitor cell input can restore medullary oxygen dependent tubular function, despite impaired medullary blood flow and oxygen supply. This result provides a basis for adjuvant cell therapy for future renal artery stenosis angiogenesis surgery.

　　Urbieta Caceres et al. found that reversing experimental renal vascular hypertension can restore coronary microvascular function and structure. Hypertension leads to left ventricular hypertrophy and vascular disorders, and causes poor prognosis in cardiovascular disease. In the study, the use of percutaneous renal angioplasty to lower blood pressure can improve the function and structure of coronary microvessels, alleviate inflammation and fibrosis. The experiment induced the establishment of a small pig model of renal vascular hypertension by placing locally stimulated coils in the renal artery. After percutaneous endovascular renal angioplasty treatment, blood pressure and left ventricular hypertrophy were significantly reduced, microvascular permeability and response to adenosine were improved. Reversing early renal vascular hypertension can improve coronary microvascular function and structure, reverse myocardial hypertrophy and diastolic dysfunction, reduce myocardial ischemia and inflammation, suggesting that adjusting blood pressure to normal can protect cardiovascular function and structure.

　　At the same time, Urbieta Caceres and others also found that selective improvement of renal function can protect the integrity and structure of myocardial microvessels at the middle and distal ends of experimental renal vascular disease by building a miniature pig model of atherosclerotic renal artery stenosis. Atherosclerotic renal artery stenosis may damage renal function and increase cardiovascular incidence rate and mortality. However, the mechanism by which atherosclerotic renal artery stenosis affects cardiovascular function is still unknown. The purpose of this study was to investigate whether protection of renal function could reverse cardiac dysfunction in atherosclerotic renal artery stenosis. In the experiment, a miniature pig model of atherosclerotic renal artery stenosis (complicated with hypercholesterolemia and renovascular hypertension) was established. Endothelial progenitor cells were injected into the kidney six weeks later. After four weeks, the response of unilateral renal function, myocardial blood flow and microvascular permeability to adenosine was evaluated by CT. The microvascular density of myocardium was evaluated by micro CT. Simultaneously set up normal miniature pigs as controls. The results showed that the blood pressure in the atherosclerotic renal vascular stenosis group was similar to that in the combined endothelial progenitor cell treatment group. Compared with the normal group, the atherosclerotic renal artery stenosis group showed a decrease in glomerular filtration rate, and an increase in renal vein and systemic oxidized low-density lipoprotein, aldosterone, uric acid, etc. Reminder: Increased levels of renal oxidative stress and fibrosis. In addition, atherosclerotic renal artery stenosis impairs the response of myocardial blood flow and myocardial microvascular permeability to adenosine, reduces microvessel density and leads to myocardial fibrosis. Selective improvement of renal function can reduce systemic oxidative stress and inflammation to protect the distal myocardium.

　　Eirin et al also used the atherosclerotic renal artery stenosis miniature pig model to prove that mesenchymal stem cells derived from adipose tissue can improve the prognosis of angioplasty for atherosclerotic renal artery stenosis miniature pigs and restore renal function. The study found that the combination of mesenchymal stem cells supplementation and percutaneous renal angioplasty can restore the integrity of renal cells and improve the renal function of atherosclerotic renal artery stenosis miniature pigs. However, percutaneous renal arterioplasty cannot consistently improve renal function in patients with atherosclerotic renal vascular disease. Eirin et al. further found that persistent renal dysfunction in small pigs with renal artery stenosis is associated with remodeling of cortical microvessels. After percutaneous renal artery angioplasty, microvascular loss and fibrosis degree affect renal function recovery, suggesting that renal parenchymal disease should be evaluated before percutaneous renal artery angioplasty.