Telmisartan Ameliorates Renal Fibrosis Through Effecting The Expression Of Hypoxia-inducible Factor1Alpha

Objective To study the relationship between peritubular capillary regression and renaldisorder, as well as the implication of peritubular capillary regression for the diseaseprogress in IgAN.Method We collected178clinical renal biopsy specimens of IgAN patients in our hospitalfrom2009to2010. The clinical data, including hematuresis,24h proteinuria and bloodpressure, of those patients were cleared up. Renal pathological changes were evaluated withMasson, PAS and HE. Immunohistochemistry was used to detect the expression anddistribution of CD34, CD20, CD4, CD8, CD68and DC. The prognostic role ofmicrovascular over a2-year follow-up was evaluated. The relationship between peritubularcapillary regression with renal disorder and the prognostic was assessed with statisticalanalysis.Result Hematuresis, blood pressure and glomerular damage had no relationship with thepercentage of peritubular capillary positive area. The percentage of peritubular capillary positive area was negatively related with24h proteinuria, tubular atrophy, renal fibrosis andthe infiltration of inflammatory cells. Besides, comparing the microvascular positive area ofthe degree of tubular atrophy, the positive area decreased, and comparing degree2withdegree0, differences were significant, p<0.05. The result of the microvascular positive areaof the degree of renal fibrosis, comparing degree2and degree1with degree0, differenceswere all significant, p<0.05.. The correlation between microvascular positive area and CD4,CD8, CD20and CD68was0.273(p<0.01),0.284(p<0.01),0.228(p<0.05),0.196(p<0.05)respectively. Comparing the progress group with stable group, the percentage of CD34positive area decrease, p=0.0015. When peritubular capillary area was lower than3.77%,the risk of the disease progress was2.57higher.Conclusion the percentage of peritubular capillary positive area had no relationship withhematuresis, blood pressure and the glomerular damage, but was negatively related with24h proteinuria, tubular atrophy and renal fibrosis. The more serious of microvasculardamage, the poorer prognosis of the patient. Objective To assess the effect of telmisartan on the expression of hypoxia induced factor1alpha in the kidneys of unilateral ureter obstruction mouse.Method Mouse renal interstitial fibrosis was produced by unilateral ureter obstruction(UUO). Eigty male CD1mice were randomly divided into sham group(0d), UUO modelgroups of3day(3d),5day(5d),7day(7d),10day(10d) and14day(14d), UUO and telmisartan treatment (10mg.kg-1.d-1)7days(7dT) and14days(14dT) groups,10mice eachgroup. Renal pathological changes were evaluated by MASSON stain.Immunohistochemistry was used to detect the distribution of a-SMA, HIF-1a, F4/80and thecolocalization of HIF-1a and F4/80on serial sections. Western-blot was used to detect theprotein expression of a-SMA, p-AKT, p-ERK and HIF-1a.Result The expression of a-SMA and p-ERK in ureter obstruction mice increased over time(P<0.05), the expression of p-AKT and HIF-1a increased at the start and then decrease,with the peak on7day and10day each. But the decrease of HIF-1a was not obvious.HIF-1a and F4/80was colocalized in the renal interstitium. After treatment with telmisartan,the changes of them were all negative accelerated.Conclude Telmisartan through inhibiting the infiltrate of macrophage cells, delaying thechanges of p-AKT and p-ERK, decreasing the expression of HIF-α, alleviated the renalfibrosis of unilateral ureter obstrucion mouse.