Effects Of Endothelin-1 On Portal Hypertensive Vasculopathy

Objective In portal hypertensiv vasculopathy rat's models,to investigate the changes of endothelin-1 concentration,transforming growth factor(TGF-β),nuclear factor-kappaB(NF-κB) protein expression and distribution,vascular endothelial growth factor(VEGF)mRNA expression and distribution,discuss the relationship among ET-1,TGF-β,NF-κB,VEGF.By evaluating influence of ET-1 on TGF-β,NF-κB protein,to investigate the role of ET-1 in portal hypertensive vasculopathy.Methods Rats were divided in three group radomly,Portal hypertensive group,Portal hypertensive + bonsentan group and Sham operate group,detect the concentration of ET-1 with radio-immunity method,analysis TGF-βand NF-κB protein expression and distribution with immunohistochemistry method,analysis VEGF mRNA expression and distribution with in situ hybridization method,above-mentioned data were studied with image -analysis system, splanchno-vascular was studied with HE stain method and observed with microscope.All values are mean±SE.Comparisons between means of multiple groups were analyzed by one-way ANOVA and Scheff'e's multiple comparison tests.Result:1.The concentration of ET-1 was:SO(sham operate)group:142.39±5.02pg/ml, PH(portal hypertension)group:211.56±5.98pg/ml.Compare with SO and PH group data there were significant difference(P＜0.05).Bosentan group:216.20±4.48 pg/ml,it compare with PH group data there weren't significant difference(P＞0.05).2.light-microscope result display: PH group:tunica intima of portal vein is thickening and collagen fiber is hyperplastic.Smooth muscle'tunica midia and muscle fiber are predominace thickening.there are phlegmonosis cells in theca externa.After Bosentan that is ET-1's receptor antagonist was admoved,vascular lesion lessened.3.Antigen-analysis result display:(1)TGF-βexpression:SO group expression was weak.PH group expression was strong.Image analysis result display:PH group compared with SO group Integra luminance worth(1718.5±27.93)and the number of positive cell(6.61±0.15)expression was strong.The data there were significant difference (P＜0.05).Bosentan cut down TGF-βexpression.Bosentan group Integra luminance worth (1416.6±21.68)and the number of positive cell(5.22±0.25).Compared with PH group data there were significant difference(P＜0.05).(2)NF-kB expression:.Image analysis result display: PH group compared with SO group Integra luminance worth(1836.40±33.11)and the number of positive cell(9.29±0.36)expression was strong.The data there were significant difference(P＜0.05).Bosentan group compared with PH group Integra luminance worth (960.73±21.61)and the number of positive cell(6.49±0.21)expression was weak.The data there were significant difference(P＜0.05).4.hybridization in situ result display:VEGFmRNA masculine signal is buffy partical.It is in cytolymph.SO group expression is weak.PH group expression is strong..Image analysis result display:PH group compared with SO group Integra luminance worth(1706.20±34.23)and the number of positive cell(8.71±0.58) expression was strong.The data there were significant difference.(p＜0.05).and the number of positive cell(6.49±0.21)expression was weak.The data there were significant difference (P＜0.05).Bosentan group VEGFmRNA'expression descend manifestly.It compared with PH group Integra luminance worth(1070.39±15.28)and the number of positive cell(5.02±0.27) expression was weak.The data there were significant difference.(p＜0.05).Conclusion In portal hypertensive rats vasoactive substances such as ET-1 induce an increase Furthermore,we have shown that effects of ET-1 on portal hypertensive vasculopathy are very complex,probably implicating the release of one hormone by the other and the systhesis of growth factor such as TGF-β,NF-Kb and VEGF result in portal hypertensive vasculopathy happen.The striking inhibitory effect of Bosentan in ET-1 induced increasing of TGF-βNF-κB VEGF indications of ET- 1 rceptor antagonist Bosentan has therapeutic role in those situations.