| Objective To explore the intervention effect and it's mechanism of spironolactone on tubulointerstilial fibrosis of the mouse with adenine nephropathyMethods Divide the Wistar mouse into three groups: spironolactone group, adenine model group and the normal group. (1)Observe the NAG, urine protein, hematoglobulin (HGB), serum creatinine (Scr) and the changes of the disease feature of the kidney.(2)By immunohistochemistry staining, observe the expression of the CTGF, MMP-9, TIMP-1, CD14+,α-SMA, Col IV of the mouse.(3)In situ hybridization staining, observe the changes of the CTGFmRNA activity of the mouse.Results ①Compared with the normal group, the NGF activity on the other two groups is obviously on the rise and the difference is apparent. Compared with the adenine model group, the activity of the NAG in the urine of the spironolactone mouse group does not has obvious decline and the difference is quite unclear. ②In the adenine model group, the TBM of the mouse becomes thicker and the amount of matrix in the tubuloinertitium increase, the amount of the HGB decreases, and the difference is clear compared with the normal group. In the spironolactone group, except that the renal tubule is expanded, all the other marker decreased greatly. ③Compared with the normal group, the level of serum K+ other two groups is obviously on the rise and the difference is apparent ;compared with adenine model group ,the level of the serum K+ of spironolactone mouse group does not has obvious decline and the difference is quite unclear.④Compared with the normal group, the density of positive expression of CTGF, TIMP-1 increases sharply in the other two groups, which the rate of MMP-9/TIMP-1 declined greatly. Compared with the adenine model group, the expression of the CTGF, TIMP-1 greatly declined in the renal tubulointerstitium in the spironolactone group, and the rate of MMP-9/TIMP-1 rises considerably. ⑤ Compared with the normal group, in the other two groups, the positive staining area of α-SMA and Col IV in the renal tubulointerstitium rises obviously and the difference is great. Compared with the pan model group, the positive staining area of α-SMA and Col IV in the renal tubulointerstitium in the spironolactone group declines greatly. ⑥Compared with the normal group, the number of the CD14+ cells grows greatly in the other two groups and the difference is great. Compared with the pan model group, the number of the CD14+ cells declines considerably in the spironolactone group. ⑦Compared with the normal group, in the other two groups the activity of the CFGFmRNA obviously soars and compared with the adenine model group, the activity of the CFGFmRNA in the renal tubulointerstitium in the mouse falls in the spironolactone group, and the difference is great. ⑧In adenine model group and spironolactone group, there was a positive line-correlation between the expression of CTGF of the renal tubulointerstitium and the pathological lesion in kidney tissue of rats. ⑨Certain,there was a negative line-correlation between the rate of MMP-9/TIMP-1 in renal tubulointerstitium and the expression of CTGF in kidney tissue of the rats in adenine model group and spironolactone group. Conclusion: ①The expression of CTGFmRNA and CTGF protein in the renal tubulointerstitium of the rats with adenine nephropathy increases significantly, which may induce the tubulointerstital fibrosis. ②CTGF may induced the increasing of α-SMA positive cells and infiltration of CD14+ cells in renal tubulointerstital,and decreased the ratio of MMP-9/TIMP-1, then the collagen accumulated in the tubulointerstital, which may accelerate the renal lesion. ③Spironolactone can protect the rats from tubulointerstital fibrosis. ④Spironolactone can inhibit expression of CTGF,α-SMA and Col IV, inhibit the decreasing of ratio of MMP-9/TIMP-1 and infiltration of the macrophagocytes in the tubulointerstitium of the rats with adenine nephropathy, then relieve the damage of glomeruli and tubuloiterstitium,delay...
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