[Mesangial proliferative changes and mesangiolysis. Habu-snake venom induced glomerular lesions of the kidney]

Abstract

Proliferative changes of the glomerular mesangium of the kidney are generally considered to be a progressive inflammatory process of glomerulonephritis. There are several reports on experimental glomerulonephritis induced by snake venom which is known to cause demonstrable mesangiolytic changes in the glomerulus. The author investigated the sequential morphological changes of the renal glomerulus by light and electron microscopy after administration of 1.0 mg/kg of Habu (Trimeresurus flavoviridis) snake venom to 56 guinea-pigs via tail vein injection. In addition, an analysis of proliferated cells in the glomerulus was attempted by applying the immunostaining method for the antibody to BrdU as the marker of the dividing cells. Various degrees of mesangiolytic changes of the glomerulus were induced after Habu venom injection. In this model, however, the majority of mesangiolytic changes were mild. Subsequent segmental nodular proliferation of the mesangial cells was observed in mesangiolytic areas. Mitotic figures appeared from 24 hours to 7 days after the venom injection, as shown by BrdU staining. New capillary lumens were formed among the proliferated cells of the postmesangiolytic segment 4 to 5 days after the venom injection. Formation of capillary lumens and reconstruction of the glomerular loops had been gradually established through the time course. The histological structure of the glomeruli returned almost to normal 15 weeks after the venom injection, with occasional features of remolded-healing, although a small number of glomeruli still showed persisted mild segmental mesangial proliferation as well as mild increase of PAM-positive substance in the mesangial area. These results suggest that mesangial proliferation is related to the reconstruction of the glomerulus rather than the progression of the glomerular lesions, at least in this model. The author postulates that the mesangial cell has the functional ability to repair the injured glomerular structure. The application of the BrdU immunostaining method turns out to be a useful tool for analyzing the relationship between cell mitosis and cell proliferation. In the guinea-pig, the Habu-snake venom induced mesangiolytic lesions are milder than those in the rabbit and the rat and the degree of subsequent mesangial proliferative changes is less prominent.