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Lesions and peritubular capillaries of renal interstitial fibrosis lost Objective To observe unilateral ureteral obstruction (unilateral ureteral obstruction, UUO)-induced rat renal interstitial fibrosis model using a new type of immune modifier FTY720 its intervention, observe its impact on the loss of renal interstitial fibrosis and peritubular capillaries and prevention role, and to explore its mechanism. Methods 45 SD rats were randomly divided into three groups, the sham-operated group (SHAM), model group of unilateral ureteral obstruction (UUO) and FTY720 treatment group (FTY720), 15 in each group. Model group and FTY720-treated rats underwent unilateral ureteral obstruction surgery, sham group laparotomy without ligation of the ureter, suture the abdominal cavity, as a control group. Normal saline treatment group given FTY720 0.5mg · kg-1 · d-1 gavage, model group and the sham group three days before surgery, three group was given until the animals were killed. Each group rats were sacrificed after 7, 14, 21 days each five, each group of rats were placed in metabolic cages before being killed specimens from 24-hour urine, urinary protein excretion. Determination of serum blood Scr, BUN and blood collection through the heart. Obstructed kidney tissue specimens after the rats were sacrificed HE and MASSON staining renal interstitial fibrosis with the Tunel assay tubular cell apoptosis, determined by immunohistochemistry in renal tissue CD3, ED1, α- smooth muscle actin (alpha-SMA), collagen - Ⅲ (COL-III), CD141, VEGF expression levels. Results 24h urinary protein, 14d after model group (15.48 ± 1.52) mg · d-1 of FTY720 treatment group (9.7 ± 1.74) mg · d-1, significantly lower compared with the model group, the difference was statistically significant ( P lt; 0.05). 14, 21 days after surgery, the model group, serum creatinine (Scr) levels, respectively (123 ± 15.76) μmol · L-1, (65.88 ± 6.08) μmol · L-1, (51.38 ± 6.9) μmol · L- 1 of FTY720 treatment group, serum creatinine corresponding (41.76 ± 4.51) μmol · L-1, (39.54 ± 7.94) μmol · L-1 (38.5 ± 4.52) μmol · L-1, were significantly lower (P lt; 0.05 ) of FTY720 treatment group and the sham group showed no significant difference. 7 and 14 days after surgery, the model group BUN (16.14 ± 3.21) mmol · L-1 (10.7 ± 1.66) mmol · L-1, of FTY720 treatment group BUN were (8.08 ± 0.96) mmol · L-1 The difference was statistically significant (P lt; 0.05) and (6.98 ± 0.80) mmol · L-1, there is a certain degree of decline,. Pathological examination of FTY720 treatment of renal interstitial fibrosis compared with the model group was significantly reduced. Immunohistochemical results showed that the sham group renal interstitial point in time were no inflammatory cell infiltration, a large number of model group after seven days of renal interstitial CD3, ED1 cell infiltration, 14 and 21 days increased significantly, with model compared of FTY720 treatment of renal interstitial CD3, ED1 of cell number to a certain extent reduced (P lt; 0.01). α-SMA expression limited to the blood vessels in the sham group, FTY720 treatment group and UUO model group was significantly increased, visible in the tubular and interstitial cells, FTY720 treatment group expression to be weaker than the model group. Sham group each time point of renal interstitial visible in a small amount of type III collagen expression, model group after surgery, 14 and 21d expression of collagen type III was significantly enhanced, mainly focused on the obvious area of ??tubulointerstitial lesions, expression of FTY720 treatment group significantly reduced. Sham group renal interstitial microvascular no obvious lesions, after 14, 21 days CD141-positive capillary density were 158.6 ± 8.29,155.2 ± 5.89,157 ± 4.47, model group, renal interstitial microvascular disease serious, focused apparent area of ??the renal tubule injury, CD141-positive capillaries progressive decrease, 14, 21 days after surgery, respectively 116.8 ± 8.92,98.8, ± 3.96,62.2 ± 7.01. FTY720 treatment can significantly reduce the capillary lesions and lost 14, 21 days after the capillary density were 132.5 ± 8.32,119.4 ± 12.21,85 ± 2.59, significantly higher than the model group (P lt; 0.01). Immunohistochemical results showed that the sham group at each time point were no significant apoptosis model group seven days after see tubular epithelial cell apoptosis with extend the time of obstruction of apoptotic cells was significantly increased trend, while FTY720 treatment group at each time segment tubular epithelial apoptosis were lower than the model group (P lt; 0.01). Tubular epithelial cells of the sham group visible expression of the more VEFG protein, the model group were 14, 21 days VEFG protein expression was gradually decreased inflammatory cell infiltration at almost no expression of VEGF. Compared with the model group of FTY720 treatment group renal tubular epithelial cells VEGF protein expression was higher than the model group (P lt; 0.01), but lower than the sham group (P lt; 0.05). Conclusion novel immunomodulatory agent FTY720 significantly reduce interstitial T lymphocyte and macrophage infiltration in UUO rats, thereby reducing apoptosis of renal tubular epithelial cells, up-regulating VEGF expression, decrease in renal interstitial capillary loss, and FTY720 in to some extent, can inhibit renal tubular epithelial cell transdifferentiation and extracellular matrix accumulation, significantly reduced the degree of rat renal interstitial fibrosis after unilateral ureteral obstruction, has a protective effect on renal function.
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