Effectsof Estradiol On Renal Remodeling In Angiotensin ? Induced Ovariectomized Mice

Objective:To explore estradiol in ovariectomized mice induced by angiotensin?in blood pressure,kidney renal remodeling and oxidative stress.Method:1?8 week-old SPF C57BL/6 female mice were randomly divided into 9 groups,?1?control group,?2?Sham group,?3?control group+oil group,?4?OVX?ovariectomized?group,?5?Sham+Ang?group,?6?OVX+Ang?group,?7?Sham+Ang?+E2 group,?8?OVX+Ang?+E2 group,?9?OVX+Ang?+Valsartan?Dovan?group.After the surgery,?7?and?8?groups were administrationed estradiol?200ug/kg??dissolved in olive oil?per day subcutaneously from the next day.?4?group underwent daily subcutaneous administration of the same dose of olive oil.2 weeks after the surgery,?5??6??7??8??9?groups were subcutaneously implanted osmotic pump containing Ang?[1000ng/?kg·min?].The next day after the implantation,?9?group was given Valsartan?20.8mg/kg?Capsule by oral gavage every day,Continued four weeks.2?The blood pressure of the mice in each group was measured with the non-invasive measurement of blood pressure after 0 week,2 weeks,4 weeks and 6 weeks,respectively.3?After 6 weeks mice were sacrificed to extract serum.The xanthine oxidase and thiobarbituric acid?TBA?method were employed to test mouse serum SOD and serum MDA in mice.4?HE and Massonstaining was applied to measure the mouse the ratio of renal tubular area,and Masson staining measure perivascular collagen area?PVCA?/vascular lumen area?VLA?ratio.5?Immunohistochemistry was used to detect the expression of TGF beta 1?TGF-beta1?,NOX2 and NOX4 protain in mice kidney.Result:1.Compared with the blank group?Sham group and blank-oil group,the OVX group at the end of 6 weeks SBP,PVCA/VAL of renal interstitial vessels and serum MDA increased significantly?P<0.05?,serum levels were significantly decreased.while the serum SOD was significantly lower?P<0.05?.2.After implanted Ang?,the Sham+Ang?group compared with the Sham group and the OVX+Ang?group compared with OVX group at the end of 4 and 6 weeks SBP,the ratio of renal tubular area,PVCA/VAL of renal interstitial vessels,serum MDA,TGF-?1?NOX2 and NOX4 protein expression levels significantly elevated?P<0.05?,while the serum SOD significantly decreased?P<0.01?.3.Compared with Sham+Ang?group,the OVX+Ang?group at the end of 4 and 6weeks SBP,PVCA/VAL of renal interstitial vessels,serum MDA,Renal NOX2 protein significantly increased?P<0.05?,whereas the serum SOD significantly decreased?P<0.05?.4.Sham+Ang?+E₂ groupCompared with Sham+Ang?group,There was no significant difference at the end of2,4 and 6 weeks SBP,PVCA/VAL of renal interstitial vessels,serum MDA,SOD and Renal NOX2,NOX4,TGF-?1protein expression levels of Sham+Ang?+E2 group?P>0.05?,Except the ratio of renal tubular area?P<0.01?.5.Compared with OVX+AngII group:OVX+AngII+E2 group and OVX+AngII+Valsartan group of SBP at the end of the 4th and 6th weekend,the ratio of renal tubular area,PVCA/VAL of renal interstitial vessels,serum MDA,the expression of TGF-?1 protein,the expression of NOX4 protein,the expression of NOX2 protein,was significantly increased?P<0.01?;while the serum SOD significantly increased ?P<0.01??OVX+AngII+E2compared with OVX+AngII+Valsartan group:The SBP at the end of the 4th and 6th weekend,the ratio of renal tubular area,PVCA/VAL of renal interstitial vessels,the expression of TGF-?1 protein and the expression of NOX2 protein In OVX+AngII+E2 group are higher than those in OVX+AngII+Valsartan group;There was no significant difference in serum SOD,serum MDA and the expression of NOX4 protein in OVX+AngII+E2 group and OVX+AngII+Valsartan group.Conclusion:1?Ovariectomy elevated blood pressure,had a certain role of promoting at renalrenal remodeling andgoxidative stress in mice.2?That Ang?increased blood pressure,induced renal remodeling and oxidative stress could be inhibited by E₂ in ovariectomized mice,which was weaker than valsartan.3?E₂ and Valsartan may play an role in antioxidant through the pathway of NOX2/NOX4.