| Objective:To observe the change of JAK/STAT pathway in UUO rats,the influence of Astragalus and Salvia's effective components and their compatibility on Renal fibrosis was investigated.Methods:66 SD rats were randomly divided into 7 groups, the normal group, model group, fosinopril group, salvianolic acids Group, astragalus saponins group,granules compatibility of Astragalus and Salvia group,components combination of Astragalus and Salvia group. In addition to the normal group, UUO model were made by slicing on back and ligating the right ureter after anaesthesia. Besides the normal group, the model group were given the water while the other groups were given the appropriate medical treatment for 14 days after the second day. Serum creatinine (Scr) together with urea nitrogen(BUN) in blood, urinary (32-microglobulin (β2-MG) and retinol binding protein (RBP), pathology as well as collagen deposition of the nephridial tissue, I collagen (Col I), III collagen (Col III), a-smooth muscle actin (a-SMA), epithelial cadherin (E-cadherin) and modification in the JAK/STAT pathway were detected.Results:1. Renal function test results The level of serum Cr in UUO rats was higher than the normal group (P<0.05). The level of Cr in fosinopril group was significantly lower than the model group,but obvious difference was not found between the other groups and the model group(P>0.05). Discrepancy had not been found in the serum BUN(P>0.05); 2. Testing results of proximal tubular protein The components combination of Astragalus and Salvia group and the fosinopril group could reduce the urinaryβ2-MG and urinary RBP of unilateral ureteral obstruction (UUO) rat (P<0.05). The rest of the treatment groups decreased while the difference was not significant with the model group.3. Tubulointerstitial pathological changes (1) HE staining There were not any pathological changes in normal kidney.UUO groups showed a large number of atrophic tubular epithelial cells (particularly the tubular in cortex and recent marrow) with vacuolar degeneration, luminal expansion, and inflammatory cells infiltration.The pathological changes in the treatment groups improved in vary degrees.(2) Masson staining Deposition of collagen in renal tissue was not obvious.Light blue collagen could be seen in renal capsule, base material of nephric tubules, and mesenchyme in UUO groups.All the treatment groups showed less collagen deposition than the model group.4. The results of immunohistochemistry of cytokines in nephridial tissue (1)The salvianolic acids group component compatibility group and fosinopril group could reduce the expression of Col I and a-SMA in UUO rats (P<0.05).There was no significant difference (P>0.05) among the other groups even if the downtrend was existing. (2)The level of ColⅢin salvianolic acids Group, astragalus saponins group,component compatibility group and fosinopril group reduced in evidence.There was a downward trend in the other treatment groups,however, the difference was not significant (P>0.05).(3)The salvianolic acids Group,astragalus saponins group, granules compatibility of Astragalus and Salvia group,component compatibility group and fosinopril group were all able to elevate the level of E-cadherin in UUO rats.The difference was significant with the model group (P<0.05) 5.Test results of JAK2, STAT1 and STAT3 in kidney by western blot The component compatibility group, fosinopril group and granules compatibility of Astragalus and Salvia group Astragalus and its effective components can reduce the expression of JAK, STAT1, STAT3 protein in renal tissue. Astragalus saponin group was not obvious.Conclusions:Astragalus and Salvia's effective components and their compatibility may protect renal tubular function in unilateral ureteral obstruction. To a certain extent, renal fibrosis and deposit of ColⅠ,Col III and a-SMA would be alleviated and expression of E-cadhcrin would be increased. The mechanism may relate with EMT and JAK/STAT signaling pathway. |
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