| Chronic renal disease(CRF)refers to a decrease in glomerular filtration rate(GFR)caused by chronic kidney disease and a related syndrome of metabolic disorders and clinical symptoms.Various renal functions are completely lost at the end,which is known as end stage renal disease(ESRD).The disease ranks top ten in the main causes of human death,which seriously threatens people's health.The incidence of chronic kidney disease has risen in the past 30 years.The prevalence of chronic kidney disease in the United States is as high as 10.9%,and the prevalence of chronic renal failure is 7.6%.The prevalence of chronic kidney disease in China is as high as 8%-10%.The causes of chronic renal failure are complex,mainly including diabetic nephropathy,hypertensive glomerular atherosclerosis,primary and secondary glomerulonephritis,tubulointerstitial lesions(chronic pyelonephritis,chronic uric acid nephropathy,obstructive kidney disease,drug-induced kidney disease,etc.),renal vascular disease,hereditary nephropathy(such as polycystic kidney,hereditary nephritis),etc.Among them,drug-induced nephropathy is often caused by nephrotoxic drugs.Adriamycin is a common nephrotoxic drug that can cause severe kidney disease and even ESRD.For ESRD,the current clinical main treatment methods include dialysis and kidney transplantation.However,as the increasing in the number of patients,the disadvantages of both treatment methods mentioned above are becoming more apparent.Dialysis can only partially replace kidney function,and it can lead to a series of complications such as hypotension,heart failure,and arrhythmia.In addition,the cost of dialysis is high and it will bring serious economic burden to the patient's family.Although kidney transplant is the best treatment for CRF by far,it's limited due to the serious shortage of kidney sources and the long-term need for immunosuppressive drugs after surgery.As the increasing of the number of ESRD patients year by year,the donor kidney source becomes more seriously lacking.There is an urgent need to seek another effective kidney replacement therapy.In recent years,researchers have made remarkable achievements in the field of kidney regeneration,and it is hoped that a method for effectively replacing renal function can be found through engineering technology of kidney regeneration tissue.At present,kidney regeneration studies are mainly divided into renal decellularization scaffolds,iPS cell induced differentiation,blastocyst complementation,and metanephros transplantation.Among them,kidney transplantation can be developed into the structure with partial or completed renal functions by transplanting the metanephros into the proper environment of the host,further effectively improving the damaged kidney function of host,which is a promising alternative for ESRD.In recent years,studies on metanephros transplantation have mostly been conducted on the basis of a normal renal environment or a compensated renalenvironment after unilateral nephrectomy,and there are no studies on metanephros transplantation in the injured kidney environment.With the deepening of research,it's discovered that it is necessary to carry out the intervention of metanephros urinary system in order to get a better developed kidney,but the specific intervention time is not clear.This article intends to explore the metanephros development after transplantation in the environment of chronic renal faiolure and to assess the most appropriate time of metanephros urinary system intervention.Objectives:To investigate the development of metanephros after transplantation in the microenvironment of chronic renal failure and to assess the most appropriate time of metanephros urinary system intervention.Methods:Thirty male Wistar rats(250 g)were randomly divided into experimental group(n=25)and control group(n=5).Anesthesia was performed one week after the adaptive culture.The rats in the experimental group received a single tail vein injection of adriamycin(7.5 g/kg),meanwhile the rats in the control group were intravenously injected with the same volume of saline.All the rats were fed under the standard experimental animal feeding environment(room temperature 20±2° C.,relative humidity 55%±10%,day and night cycle of 12 h).All the rats were given enough food and water.After four weeks,the rats in the experimental group were further divided into adriamycin drug group(n=5),metanephros 1w group(n=5),metanephros 2w group(n=5),and metanephros 3w group(n = 5)and metanephros 4w group(n=5).The prepared metanephros were transplanted under the renal capsule of rats in the corresponding experimental group,and 24-hour urine and blood samples were collected from each group of rats weekly to detect serum creatinine(SCr),blood urea nitrogen(BUN),and 24-hour urine protein.In addition,metanephros samples of each group were collected for morphological observation and HE staining.Results:After transplantation,the metanephros developed relatively mature nephron structure.After 2 weeks of transplantation,the length of metanephros was 7-9 mm.Within 2 weeks of transplantation,the visual color of metanephros was close to that of normal kidney.After 3 weeks of transplantation,the color of metanephros was becoming while.After 4 weeks of transplantation,the metanephros color completely turned white.HE staining showed that the transplanted metanephros developed mature glomeruli and tubular structures at 2 weeks of transplantation,but tubular and glomerular atrophy occurred at 3 weeks of transplantation,coupled with interstitial fibrosis.After 4 weeks of transplantation,the metanephros condition further deteriorated,tubular and glomerular atrophy became more serious,and interstitial fibrosis was more severe.Blood biochemical tests revealed SCr(control group:4.4110.05 mg/dl,adriamycin drug group:4.20±0.05 mg/dl,metanephros transplantation group:4.36±0.05 mg/dl)and BUN(control group:17.60 mg/dl,adriamycin drug group:18.09mg/dl,metanephros transplantation group:18.72 mg/dl)showed no significant difference.24 h urinary protein(control group:25.62 mg,adrianycin drug group:183.89 mg,metanephros transplantation group:24.82 mg)showed significant differences(p<0.05).The results of immunohistochemistry showed the expression of glomerular marker NPSH2 and Pax2 was highest at the second weeks after metanephros transplantation,while the expression of NPSH2 and Pax2 was decreased at the third weeks after transplantation.Conclusions:Transplanted metanephros can develop mature glomerular and tubular structures under the microenvironment of chronic renal failure.The most appropriate time of urination system intervention is 2 weeks after metanephros transplantation. |
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