Morphometric Analysis of Glomeruli in the Experimental Rat Models of Hyperglycemia and Hyperfiltration

Shim, Young Woong; Sol, Mee Young; Lee, Kyeong Min; Choi, Kyung Un; Kim, Jee Yeon; Lee, Jin Sook; Park, Do Youn; Lee, Chang Hoon; Suh, Kang Suek

Abstract

OBJECTIVE
Diabetic nephropathy and ablation nephropathy are characterized by sclerotic processes in the glomeruli. To elucidate the site, degree and time-honored changes of glomerular sclerosis, morphometric analysis was performed using the experimental animals models.
METHODS
The animals used were male Sprague Dowley rats and separated into 4 groups as young normal control, old control, streptozotocin-injected group, and right nephrectomized group. Chronologically kidney specimens were obtained after each treatment and processed to evaluated histologic changes. To evaluated the glomerular area, interstitial fibrosis and glomerular tuft fibrosis, the kidney specimens were fixed in Buin's solution, paraffin-embedded and 2 micrometer sections were Sirius red stained. To study the mesangial area, mesangial matrix area, glomerular basement membrane, and tubu lar basement membrane, the specimens were fixed in 2.5% glutaraldehyde, epon-embedded, double-stained and examined under the transmission electron microscope. All the specimens were analyzed morphometrically using the Image Pro Plus software. The obtained morphometric data were statistically analyzed to evaluate the differences of fibrotic processes and degree between experimental groups.
RESULTS
Diabetic group revealed statistically significant increase of glomerular area from 8th week after streptozotocin injection to 24th week of experimental date. The parenchymal fibrosis and glomerular tuft fibrosis was prominent from the 2nd week of injection and steadily increased until the end of experimental date. The thickness of glomerular basement membrane was significantly increased even at the first week of injection and the tubular basement membrane also increased in thickness at the 3rd week of experiment. Ablation nephropathy model made by right nephrectomy showed increased glo merular area at the 7th week of ablation and the degree were intensified after 16th week of experimental date. The amount of stainable collagen in the renal parenchyme and glomerular tuft increased in the second week kidney sample and steadily increased thereafter until the end of experimental date. The increase of thickness of GBM and TBM also started to appear at the second week of operation. The old control also revealed fibrosis but the degree was less than the diabetic and ablation groups. Both diabetic and ablation nephropathy groups exhibited extensive increase of glomerular area, stainable colla gen, thickness of GBM and TBM at the end of experimental date and the ablation group revealed more extensive evidences of fibrosis without statistical significance. Comparison between the experimental groups were meaningless because the duration of the experimental manipulation was not the same.
CONCLUSION
Glomerular and renal interstitial sclerosis and thickening of GBM and TBM are not the specific lesions of the diabetic glomerulopathy and are the common histologic changes occur in the kidney of partial parenchymal loss of any etiology. And it is suggested by this study that the common hemodynamic change involving the diabetic nephropathy, ablation nephropathy and physiologic aging is one of the important pathogenetic factors of glomerular sclerosis.