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Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure

World Journal of Gastroenterology 2015年第14期21卷 4126-4135页

作者： Nicholas G Theodorakis Yining N Wang vyacheslav a korshunov Mary A Maluccio Nicholas J Skill Division of Transplant Surgery Department of SurgerySchool of MedicineIndiana University School of Medicine University of Rochester

AIM: Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and *** reports have suggested that the compound thalidomide attenuates portal hypertension(PHT).However, the mechanism for this action is not fully *** hypothesis is that thalidomide destabilizes tumor necrosis factor α(TNFα) mR NA and therefore diminishes TNFα induction of nitric oxide synthase(NOS) and the production of nitric oxide(NO).To examine this hypothesis, we utilized the murine partial portal vein ligation(PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout ***: Wild type, inducible nitric oxide synthase(i NOS)-/- and endothelial nitric oxide synthase(e NOS)-/-mice received either PVL or sham surgery and were given either thalidomide or *** nitrate(total nitrate, NOx) was measured daily for 7 d as a surrogate of NO *** TNFα level was quantified by enzyme-linked immunosorbent ***α m RNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain *** was determined by recording splenic pulp pressure(SPP) and abdominal aortic flow after 0-7 *** to thalidomide was determined by measurement of SPP and mean arterial pressure(MAP).RESULTS: SPP, abdominal aortic flow(Qao) and plasma NOx were increased in wild type and i NOS-/-PVL mice when compared to sham operated control *** contrast, SPP, Qao and plasma NOx were not increased in e NOS-/- PVL mice when compared to sham *** TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA ***, the effect of thalidomide on serum TNFα levels was undetermined in wild type, e NOS-/-or i NOS-/- *** acutely increased plasma NOx in wild type and e NOS-/- mice but not i NOS-/-***, thalidomide temporarily(0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, e NOS-/- and i NOS-/- PVL mice, aft

关键词： Portal hypertension Thalidomide Nitric oxide Knock

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