| Object: To observe the preventive and therapeutic effect of antioxidant Ebselen and/or VitE on hypertensive kidney damage in NO- deficient rats induced of L-NAME.Materials and methods: 64 Wistar rats were divided randomly into 8 groups (n=8): Normal group(C); Experimental control group(L); Preventative group(S1)/ therapeutic group(S2) of Ebs; Preventative group(V1)/ therapeutic group(V2) of VitE; Preventative group(D1)/ therapeutic group (D2)of Ebs and VitE, administered by gavage method. We collected urin of rats in 24 hours and measured their weight and systolic blood pressure (SBP) fortnightly. The rats were killed after 8 weeks. Plasma and homogenate of right kidney were collected for biochemical indexes examination such as NO, ACE, AngII, SOD, GSH-px, MDA, Scr and O2-.And the expression of MCP-1and NF-k B p65 protein in homogenate of right kidney were measured by Western blotting. The left kidneys were performed pathomorphologic analysis.Results:①SBP of the rats increased gradually and arrived to 142.1±7.69 mmHg after 2 weeks, but there was no obvious difference among these experimental groups. After 8 weeks, SBP of all rats in experimental groups was obviously higher compared with C (P<0.001), and SBP of the antioxidant teams was lower than L (P<0.05). SBP of the preventative administration groups were slightly lower than that of the therapeutic administration group (p>0.05). SBP of D1 was obviously lower than that of S1 (p<0.01), and SBP of S1 was fairly lower than that of V1 (P<0.05).②The NO level, the activity of GSH-PX and SOD in the serum and the renal cortex of each experimental group were obviously lower than those in C, and those in the antioxidant groups were predominantly higher than those in L(p<0.05), the combination groups more higher (p<0.05).And those in Ebselen groups were higher than those in VitE groups (p<0.05). The NO level in V1 and D1 was higher than that in V2 and D2 obviously (p<0.05), and that in S1 was slightly higher than that in S2 (p>0.05). The activity of GSH-px and SOD in the serum and the renal cortex, as well as the NO level in the renal cortex of S1, V1 and D1 were slightly higher than those in S2, V2 and D2 (p>0.05).③The level of MDA in the serum and the renal cortex, the level of SCr in the serum and the O2- content in the renal cortex obviously increased as being compared with C (p<0.05),but those in antioxidant groups increased less as being compared with those in L (p<0.05), the combination administration group increased less than the single administration groups, and Ebselen groups increased less than VitE groups (p<0.05); the preventative groups all increased slightly less than the therapeutic groups (p>0.05).④There were no obvious difference of AngII and ACE activity in plasma among groups;the level of AngII and ACE in the cortex of each experimental group were obviously higher than those in C(P﹤0.05),but the antioxidant groups increased slightly as being compared with L(P﹤0.05).The levels of AngII and ACE in the cortex of combination administration groups increased less than those in single administration groups (P﹤0.05),those in Ebselen groups increased obviously less than those in VitE groups(P﹤0.05). those in preventative groups increased slightly less than those in therapeutic groups(P﹥0.05).⑤The urine protein andβ2 microglobulin increased gradually in the experimental groups, and after 8 weeks increased obviously as being compared with those in C(P﹤0.01),those in the antioxidant groups decreased obviously than those in L(P﹤0.05),those in the combined administration groups were less than those in Ebselen groups(P﹤0.05),those in Ebselen group were less than those in VitE group(sP﹤0.05),the preventative groups decreased slightly than the therapeutic groups(P﹥0.05).⑥As for the protein expression of MCP-1 and NF-κB p65 in the renal tissue, L increased obviously than C(P﹤0.05), the antioxidant groups decreased differentially being compared with L.⑦glomerular sclerosis and interstitial fibrosis in L was seriously, and those in each antioxidant groups were slightly than those in L.Conclusion Oxygen free radical promote the hypertensive kidney damage induced by the NO-deficiency;Ebselen and VitE exert their protective role in the NO-deficient hypertensive kidney damage. Ebselen is better than VitE, and the combination is better than single used;In this experiment, antioxidant precaution seem better than given the antioxidant after two weeks when HBP occur, though no statistical significance, maybe gets some suggests that the more early the antioxidants were used, the more protection would be got on the hypertensive kidney damage induced by NO-deficiency. |
PDF Full Text Request