Nejvíce citovaný článek - PubMed ID 35344670
Pathophysiological analysis of uninephrectomized db/db mice as a model of severe diabetic kidney disease
UNLABELLED: This study aims to explore the correlation between renal blood perfusion (RBP) and diabetic nephropathy (DN). METHODS: A total of 72 mice included db/db and db/m mice at the ages of 6, 14, and 22 weeks, forming six groups. RBP was assessed using Laser Speckle Contrast Imaging (LSCI). Kidney function markers and the extent of pathological damage were evaluated. Pearson correlation analysis was employed to predict the relationship between RBP and various indicators of kidney damage. RESULTS: Compared to db/m mice of all ages, 6-week-old db/db mice showed no significant difference in kidney function markers and had no apparent pathological damage. However, db/db mice at other ages showed deteriorating kidney functions and evident pathological damage, which worsened with age. The RBP in db/m mice of all ages and 6-week-old db/db mice showed no significant difference; however, RBP in db/db mice demonstrated a significant declining trend with age. The correlation between RBP and kidney damage indicators was as follows: 24 h urinary microalbumin (r=-0.728), urinary transferrin (r=-0.834), urinary beta2-microglobulin (r=-0.755), urinary monocyte chemoattractant protein-1 (r=-0.786), Masson's trichrome staining (r=-0.872), and Periodic Acid-Schiff staining (r=-0.908). CONCLUSION: RBP is strongly correlated with the extent of diabetic kidney damage.
- MeSH
- diabetes mellitus 2. typu * komplikace patofyziologie MeSH
- diabetické nefropatie * patofyziologie patologie etiologie MeSH
- experimentální diabetes mellitus komplikace patofyziologie MeSH
- ledviny patologie krevní zásobení MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- renální oběh * MeSH
- stárnutí patologie MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In patients with diabetic kidney disease (DKD), the estimated glomerular filtration rate (eGFR) or creatinine clearance rate (Ccr) is always used as an index of decline in renal function. However, there are few animal models of DKD that could be used to evaluate renal function based on GFR or Ccr. For this reason, it is desirable to develop animal models to assess renal function, which could also be used for the evaluation of novel therapeutic agents for DKD. Therefore, we aimed to develop such animal model of DKD by using spontaneously hypertensive rat (SHR)/NDmcr-cp (cp/cp) rats with the characteristics of obese type 2 diabetes and metabolic syndrome. As a result, we have found that unilateral nephrectomy (UNx) caused a chronic Ccr decline, development of glomerular sclerosis, tubular lesions, and tubulointerstitial fibrosis, accompanied by renal anemia. Moreover, losartan-mixed diet suppressed the Ccr decline in UNx-performed SHR/NDmcr-cp rats (UNx-SHR/cp rats), with improvement in renal anemia and histopathological changes. These results suggest that UNx-SHR/cp rats could be used as a DKD model for evaluating the efficacy of therapeutic agents based on suppression of renal function decline.
- MeSH
- diabetes mellitus 2. typu * MeSH
- diabetické nefropatie * MeSH
- krysa rodu Rattus MeSH
- losartan MeSH
- metabolický syndrom * MeSH
- potkani inbrední SHR MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- losartan MeSH