| Objective: To establish the experimental Masugi nephritis model in rabbits and to investigate the therapeutic effects of small molecular peptide CMSO 10,26 and its therapeutic mechanisms.Methods: The sheep was immunized with rabbit kidney cortex, and proper volume of the sheep anti-rabbit kidney cortex serum was decided and iv. injected into rabbits to reproduce the rabbit Masugi nephritis model. The rabbits were randomly divided into 5 groups: CMS010.26 high dose group(107.3ug/kg/d), low dose group(58.5ug/kg/d) . dexamethasone treated group(0.1mg/kg/d) saline control group and normal control group. Anti-rabbit kidney cortex serum was iv. injected into rabbits except the normal control group, 0.5ml each time, once every 30 minutes, all 4 times; the normal control group was iv. injected with equal volume normal sheep serum. From next day, the corresponding drugs were iv. administered daily; the normal control group remained untreated. All the animals were detected 24 hours urinary protein serum BUN, CR every week. The kidney specimen were collected 28 days later for morphological studies(including HE staining, immunofluorescence staining and electron microscopy examination), and serum and kidney cortex MDA, SOD content macrophage immunohistochemistry staining were detected and the effects of CMS010.26 on health mice immune function were evaluated.Results: (1) Masugi nephritis model establishing: 1.2ml anti-rabbit kidney cortex serum injected dose group urinary protein and serum BUNU CR increased lightly, and turned back soon; a few glomerular crescents were observed. 2.0ml dose group urinary protein and serum BUN > CR increased significantly; glomerular hypercellularity, crescents and protein casts were observed. High level of urinary protein and serum BUNK CR were observed in 3.2ml groups; most of the glomerular Bowman's capsule were blocked completely, even fibrosis, and had significant glomerular hypercellularity, more protein casts in tubular, more inflammatory cells infiltration,and this group had high mortality that one of three rabbits died before the experiment finished. 4.0ml dose group animals died in two weeks after injection of anti-serum. Immunofiuorescence staining in 1.2ml group revealed that only few sheep IgG , rabbit IgG deposited in a "liner" pattern alongwith the glomerular GBM. 2.0mh 3.2ml group had more sheep IgG-. rabbit IgG deposit along with the glomerular GBM. 4.0ml group had no immunofluorescence staining since the rabbits died early. Normal group had neither sheep IgG nor rabbit IgG depodit along with the glomerular GBM. Decided 2.0ml was the anti-rabbit kidney cortex serum dose for rabbit Masugi nephritis model reproducing. (2)Drug therapy: CMSO 10.26 was used to therapy rabbits Masugi nephritis(established model with 2.0ml anti-rabbit kidney cortex serum). The results indicated that urinary protein was lower than saline group from the first week,and more significant in the third and forth week. Serum BUN obviously lower than saline group during the whole experimental process. Serum CR in CMSO 10.26 high dose group and low dose group were increased slightly from the second week and evidently lower than saline group. HE staining indicated that in CMSO 10.26 high dose group and low dose group the level of glomerular crescents , glomerular swelling,cells in glomerular were all mild than saline group; sheep IgG > rabbit IgG deposited along with GBM were all less than saline group revealed by immunofluorescence staining. Electron microscopy examination indicated that the GBM swelling,thickening and protein depositing were .all obviously ameliorated than saline group. Kidney damages were mild than saline group. (3)Mechanisms: macrophage infiltration was lower than saline group, serum and kidney cortex MDA content decreased than saline group, SOD content elevated than saline group; CMSO 10.26 can inhibit health mice cellular immunity and humoral immunity.Conclusions: The proper volume of the sheep anti-rabbit kidney cortex serum in our laboratory to establish rabbit Masugi nephriti...
|
PDF Full Text Request