ABSTRACT
Objective To explore the effect of Bailing capsule on epithelial-mesenchymal transition( EMT) in rats with adenine-in-duced tubulointerstitial fibrosis. Methods Tubulointerstitial fibrosis animal models were established and SD rats were divided into mo-del group ( n = 30), treatment group ( n = 30) and control group( n = 30), randomly. Experimental rats were harvested at 7 w, 12 w,17 w after onset of experiment and functional evaluations were performed. Histology, immunohistology were examined to investigateboth histolopathology changes and the expression of bone morphogenic protein-7 (BMP-7), transforming growth factor-β1 (TGF-β1 )and a-smooth muscle actin (α-SMA) in kidneys at three time points mentioned above, respectively. Results Compared with controlgroup, 24 h urinary protein in model group lost increasingly and significantly difference appeared at three time points relative to controlgroup ( P ＜ 0.01 ). Urinary NAG in model group was markedly higher than that in control group from 7 w after onset (P ＜ 0.01 ) andwas increasingly raised at 12 w and 17 w (P＜0.01). The value of blood BUN and Cr in model group increased at 7 w (P＞0.05) rel-ative to control group. There was significant difference at 12 w and 17.w (P ＜ 0.01 ). Histologically, kidneys in model group, at 7 w,exhibited tubular casts and gently tubular dilation, granuloma in cortex, mononuclear cells infiltration in tubulointerstitial areas, andmild interstitial fibrosis. At 12 w, the degree of tubular injury and tubulointerstitial fibrosis gradually aggravated. Up to 17 w, diffusetubular dilation or atrophy was observed and focal tubules disappear. Diffuse interstitial fibrosis was exhibited. In normal kidneys, im-munohistochemistry suggested that the light expression of BMP-7 was detected in proximal renal tubular epithelial cells and marked ex-pression was identified in distal tubule, collecting duct, and renal tubular epithelial in junction area between cortex and medulla. How-ever, the expression of BMP-7 in kidneys of model group significantly decreased with increasing tubulointerstitial fibrosis and was nega-tive correlation with the expression of TGF-β1(r = -0. 981 P＜0.01) and α-SMA (r= -0.975 P＜0.01). Bailing capsule ad-ministration protected the expression of BMP-7 and reduced TGF-β1 and α-SMA expression before 12 w(P＜ 0.01 ). Conclusions Ourstudy shows an anti-fibrotic reno-protective function of Bailing capsule in rats with tubulointerstitial fibrosis via prevention of epithelial-mesenchymal transition at early stage. However, the beneficial effect lost with increasing tubulointerstitial fibrosis.
ABSTRACT
Objective To observe the expressions of transforming growth factor-?1(TGF-?1) and plasminogen activator inhibitor-1(PAI-1) mRNA in tubulointerstitial fibrosis( TIF ) rats,and explore the effects of TGF-?1 and PAI-1 on TIF and the interaction between TGF-?1 and PAI-1.Methods Sixty male SD rats were randomly divided into sham operation group (SOR group,n=30) and unilateral urethral obstruction group(UUO group,n=30).TIF model was established via UUO.At d 7,d 14,d 21 after operation,10 rats of every group were killed to obtain renal samples.Histological changes were observed in tubulointerstitium injury under microscope;mRNA and proteins of TGF-?1 and PAI-1 were detected by real-time PCR assays and Western blotting respectively at d 7,d 14,d 21 after experiment onset.SPSS 10.0 software was used to analyze data.Results 1.HE,Masson staining of renal tissues of all groups indicated that there were no fibrosis in SOR rats,there were vacuole degeneration in tubular epithelial cells and inflammatory cell infiltration in tubulointerstitial in UUO rats at d 7,fibrosis aggravated gradually and became severe fibrosis at d 21.2.The expression locations of TGF-?1 and PAI-1 were renal sites of fibrosis by immunohistochemical staining.The mRNA and proteins of TGF-?1 in rats from SOR groups were lower than those of UUO groups at d 7,d 14,d 21(P
ABSTRACT
Objective To explorethe effect of Bailingcapsule on epithelial-mesenchymal transition(EMT) inrats withadenine-in-duced tubulointerstitial fibrosis .Methods Tubulointerstitial fibrosis ani mal models were established and SDrats were dividedinto mo-del group (n=30) ,treatment group (n=30) andcontrol group(n=30) ,randomly .Experi mental rats were harvested at 7 w,12 w,17 wafter onset of experi ment and functional evaluations were performed. Histology ,i mmunohistology were examined to investigateboth histolopathology changes and the expression of bone morphogenic protein-7 (BMP-7) ,transforming growth factor-?1(TGF-?1)and a-smooth muscle actin (?-SMA) in kidneys at three ti me points mentioned above ,respectively .Results Compared with controlgroup ,24 h urinary proteinin model grouplost increasingly and significantly difference appeared at three ti me points relative to controlgroup(P0 .05) rel-ative to control group.There was significant difference at 12 wand 17 w(P