Abstract:

Abstract： Objective To study the expressions of Ki67 and mTOR in Thy-1 nephritis model of rat who were given
1
,25-dihydroxyvitamin D3[1,25(OH)2D3] and to explore its mechanism. Methods Healthy male SD rats (n=90) were random⁃
ly divided into three groups: control group, model group, 1,25(OH)2D3 treatment group (n=30 in each group). Model group
and 1,25(OH)2D3 treatment group were intravenously injected with anti-Thy1 monoclonal antibody once via tail vein while
the control group were administrated with same volume of normal saline through the same route. 1,25(OH)2D3 were adminis⁃
trated at 0.5 μg per day intra-gastrically for consecutive 21 days in 1,25(OH)2D3 treatment group while equal volume of pea⁃
nut oil were given in control group and model group. Six rats were randomly selected from each group and sacrificed at the
1st , 3rd , 7th , 14th and 21st after drug intervention. Twenty four hour urine sample were collected in each rat just before it was
culled to detect 24-hour urinary protein excretion. Renal tissue samples were harvested and stained with hematoxylin & eo⁃
sin (H&E) and PAS to determine the renal pathological variation and the expressions of mTOR and Ki67 were assessed by
immunohistochemistry. Results Urine protein begin to be detected at the first day after model was established, peaked at
the 3rd days then started dropping until the 14th day when urine sample turned to normal. Urine protein levels were lower in 1,
25(OH)2D3 treatment group at the 1st,3rd,7th day after model establishment than those in model group(P < 0.05). Compared with
model group, the pathological damage of renal tissue in 1,25(OH)2D3 treatment group were alleviated at the 3rd and 7th day after
model establishment (P < 0.05). Expressions of Ki67 and mTOR in 1, 25(OH)2D3 treatment group were reduced compared
with those in model group (P < 0.05). Twenty four hour urinary protein and expressions of Ki67 and mTOR as well as renal
pathological damage were all positively correlated with each other. Conclusion 1,25(OH)2D3 can inhibit the proliferation of
glomerular mesangial cells in Thy-1 nephritis model of rat. And its therapeutic mechanism may be associated with down reg⁃ulating expressions of Ki67 and mTOR.

Key words: vitamin D, proteinuria, mTOR, Ki67, 1,25(OH)2D3, Thy-1 nephritis