Changes Of Calcitonin Gene-related Peptide And Endothelin-land Their Effects In Rats With Acute Renal Failure

[Objective] To study changes of CGRP and ET-1 and their effects in the process of ARF, and then provide the theoretic basis for the mechanism, prevention and treatment of ARF.[Methods] 122 male Wister rats, 180-200 grams, were randomly divided into normal and 1h, 3h, 6h, 12h, 24h, 48h, 72h and 7d groups after glycerol intramuscular injection and CGRP intravenous injection. CGRP was injected 5-10 minutes after glycerol injection in treatment group. We observed dynamically renal function indexes and histopathological changes by light microscope. We detected and analyzed the changes of the content of CGRP and ET-1 in serum, urine and renal homogenization of ARF rats by radioimmunoassay, and also utilized immunohistochemistry method in the study of the distribution and content of CGRP and ET-1.[Results] 1. In rat ARF model by glycerol intramuscular injection, renal function changes occurred early and pathological morphology changes were serious, so it is a typical ARF model. 2. Pathological morphology changes: (1) at early stage (lh-12h)of ARF, major changes were hemodynamic abnormality and injury of glomerulus's capillary endothelium cells;(2)at middle phase(24h-48h), there were serious renal tubule necrosis;(3) at late phase (72h-7d), renal tubule epithelial cells' proliferation and compensative dilation were obvious. In CGRP treatment group, the important changes were hyaline degeneration, but no obvious necrosis of renal tubule. 3. CGRP was mainly distributed in the epithelium cells of the distal convoluted tubule, collecting tubule and glomerulus's capillary endothelium cells in kidney using immunohistochemistry method. And ET-1 was mainly distributed in proximal convoluted tubule, distal convoluted tubule and collecting tubule. 4. In ARF rats, ET-1 of renal tissue, serum and urine increased in 1h-3h group, but decreased in 72h group, and were approximately normal in 7dgroup. In early stage of ARF, CGRP of serum increased, but CGRP of urine and renal tissue decreased obviously and were lowest in 24h group and began to increase from 7d. CGRP related negatively with ET-1. 5. Renal function changes and pathological injury were obviously relieved and ET-1 of serum reduced in CGRP treatment group compared with glycerol injury group. [Conclusions] 1. In ARF , CGRP related negatively with ET-1 in serum and urine and CGRP was decreased along with the serious extent of ARF. 2. The content of CGRP and ET-1 in serum and urine could reflect the renal function state and clinical course of ARF, so it could be a sensitive biochemistry index of ARF. 3. In early phase of ARF, enhancing the level of CGRP in vivo may be one of the ways to prevent and treat ARF. 4. Immunohistochemistry showed that CGRP was distributed in renal tubule and vessel endothelium, especially in the distal convoluted tubule and collecting tubule.