| Objectives：To compare the pathological difference of murine habu snake venom-inducedglomerulonephritis between C57BL/6and FVB/Nmice，and to provide researcherswith scientific standards for selecting better animal model.Methods：Comparative research of murine habu snake venom-induced glomeru-lonephritis between C57BL/6and FVB/N mice:8weeks old male C57BL/6mice(n=33) and FVB/N mice(n=52) were used to induce mesangial proliferativeglomerulonephritis after a singleintravenous injection ofhabu toxin(2.5mg per kgbody weight).Mice were sacrificed1,3,7,14or21days after injection and kidneyswere harvested for histologic and immunohistochemical studies. PAS staining, thenumber counting of nucleated cells in the glomeruli and pathological evaluationwere used to evaluate the renal biopsy pathology. PCNA immunohistochemistry wasused to observe cell proliferation.Results：After the model-making, the survival rate of FVB/N mice was lower thanC57BL/6mice. The renal pathological results showed typical and significantmesangial dissolution or capillarectasia on1and3days after injection. At day7,after acute mesangial injury, the lesions of glomeruli in the C57BL/6micegroupbegan with obvious cluster aggregative proliferation, mainly showed focalmoderate tosevere proliferationwith matrix accumulation, and the glomerularcapillary loop disappeared due to the expanded matrix, segmental sclerosis, globalsclerosis and balloon adhesion could be found in some glomeruli. On14days afterinjection, there were still residual matrix accumulation in some glomeruli, most ofthe glomeruli back to normal on21days. No obvious mesangiolysis was observedthroughout the experimental period in the FVB/N mice group after themodel-making. On7days after injection, the mainly changes of the glomeruli were focal mild to moderate proliferation with matrix accumulation, segmental sclerosiscould be found in very few glomeruli. Compared to controls, semiquantitativeassessment of mesangiolysis revealed a significant increase at day1and3afterinjection, on the other side, the mesangiolysis index score did not change throughoutthe experimental period in FVB/N mice groupafter the model-making. At day1and3after injection, the mesangiolysis index score was remarkablely higher in C57BL/6mice group compared to FVB/N mice group. The glomerulosclerosis index score ofC57BL/6and FVB/N mice was significantly elevated compared to controls at day7，and it was more higher in the former group.The result of the number counting ofnucleated cells in the glomeruli revealed a significant decrease at day1afterinjection and a maximal increase at day7with a subsequent decline but still elevatedmean cell count in glomeruli at day14, reaching the basal level of control animals atday21in C57BL/6mice group. The number counting of nucleated cells in theglomeruli result of FVB/N mice group showed no obvious change in other timepoint but a significant increase at day7after injection.At day7and14，the nucleatedcell count in the glomeruli of C57BL/6mice was higher than FVB/N mice.Compared to controls，a statistically significant increase in the PCNA positive ratewas observed at day3and7in both C57BL/6and FVB/N mice groups, and PCNAexpression of C57BL/6mice were significantly higher than FVB/N mice at day3.ConclusionC57BL/6mice were much more sensitive than FVB/N mice in habu snakevenom-induced glomerulonephritis, they could developed typical pathologicalevolution of the self-limited mesangial proliferative glomerulonephritis whenreceived2.5mg/kg habu toxin intravenously via the tail vein. With the samemodeling approaches for the same period, FVB/N mice did not show obviousmesangiolysis lesion in the early phase. Although there was a proliferation phase inthe later period in FVB/N model group, the pathological degree of proliferationdamage in FVB/N mice was lower than C57BL/6mice in the same period. Inaddition, FVB/N mice exhibited poorer tolerance to habu toxin with lower survivalrate after snake venom injection. |
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