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31.
32.
Thrombin Inhibition in discordant xenograft rejection 总被引:1,自引:0,他引:1
Beth-Ann Lesnikoski Daniel Candinas Ichiro Otsu Rainer Metternich Fritz H. Bach Simon C. Robson 《Xenotransplantation》1997,4(3):140-146
Abstract: Microvascular thrombosis and the associated platelet and endothelial cell activation are prominent observations in xenograft rejection. This pathological picture could be related to the excessive generation of thrombin in the context of either inflammation or putative inter-species molecular incompatibilities between activated coagulation factors and their natural anticoagulants. Relatively selective thrombin Inhibition with the serine protease inhibitor SDZ MTH 958 (MTH-958) are independent of heparinoids and anti-thrombin III. MTH-958 has been shown to significantly prolong porcine cardiac function during perfusion with human blood in an ex vivo model. The aim of this study was to validate the role of thrombin generation in a rodent model of discordant xenograft rejection in vivo. The effect of thrombin inhibition with MTH-958 was tested in both hyperacute rejection (HAR) and delayed xenograft rejection (DXR) after decomplementation with cobra venom factor (CVF) in normal Lewis (Lew) rats and Intrinsic C6 deficiency In PVG (C6-/PVG) recipient rats. Recipient rats received heterotopic guinea pig cardiac xenografts and were treated with titrated doses of MTH-958 until the time of graft rejection. Plasma samples at selected time points were examined to confirm effective thrombin inhibition, and rejected grafts were analyzed by immunohistology. MTH-958 significantly improved graft survival in HAR albeit the extent of prolongation was not marked, but the agent failed to prolong survival In CVF-treated Lew rats. In C6-/PVG rats receiving MTH-958, a significantly reduced graft survival time was observed when compared with C6-/PVG controls. The grafts from MTH-958-treated animals showed dense deposits of C3, IgM, and IgG with fibrin levels similar to controls. The thrombin antagonist tested could prolong xenograft survival during HAR but had no benefit in DXR. The relative non-specificity of the serine protease inhibitor MTH-958 with the potential activation of alternative pathway of complement via the inhibition of factor I could account for the failure to prolong xenograft survival in DXR. The pathogenetic significance of thrombin generation in this situation remains to be determined by the use of more selective and pharmacologically acceptable I anti-thrombin agents. 相似文献
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目的 研究还原型谷胱甘肽对大鼠肝星状细胞(hepatic stellate,cells,HSC)中金属蛋白酶1组织抑制因子(TIMP-2)表达的影响。从分子和蛋白水平探讨还原型谷胱甘肽对大鼠肝纤维化的作用和可能机制。方法 采用50%CCl4制备大鼠肝纤维化模型,在造模过程中给予还原型谷胱甘肽进行干预。应用RT-PCR才Western Blot技术,在分子和蛋白水平检测体外分离大鼠HSC中的TIMP-1的表达情况。结果 还原型谷胱甘肽干预组与模型组和正常对照组相比,HSC中TIMP的表达降低(P<0.05)。结论 还原型谷胱甘肽的干预可下调大鼠HSC中TIMP-1的表达,对实验性肝纤维化起到减轻作用。 相似文献
35.
新生大鼠海马神经细胞原代培养方法的改良 总被引:7,自引:1,他引:6
(1)目的:建立较理想的新生大鼠海马神经细胞体外原代培养方法。(2)方法:采用低浓度,长时间胰酶消化和机械分离相结合的方法进行单层原代培养。(3)结果:在体外培养条件下神经细胞结构特征明显化,并能形成典型的神经细胞网络。(4)结论;该培养技术是海马神经细胞体外培养的理想方法。 相似文献
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目的 :探讨奶茶对大鼠体重和血清胆固醇含量的影响。方法 :将大鼠随机分为对照、脂对照、奶、茶和奶茶五组 ;高脂饲养的同时分别用水、奶、茶和奶茶进行灌胃 ,定期测定大鼠的血清胆固醇 (TC)。结果 :实验期间奶茶组大鼠体重的增长量高于其他三个高脂饲料组 ,且明显高于对照组 (P <0 .0 5 ) ;高脂饲料组大鼠的血清胆固醇含量明显增加 ,但增长量在高脂饲料组间差异无显著性 (P >0 .0 5 )。结论 :本实验浓度的奶茶对高脂饲料诱导的大鼠血清胆固醇升高未见有降低作用 相似文献
38.
E. V. Borisova D. Yu. Rusakov S. K. Sudakov 《Bulletin of experimental biology and medicine》1992,114(3):1328-1332
39.
D. Dickerson B. Adams G. Engelbrecht G. Boltman R. Hickman D. Kahn 《Transplant international》1992,5(Z1):S63-S64
The precise cause of allograft dysfunction after renal transplantation often cannot be established by non-invasive means. In clinical practice, radionuclide scans form an integral part of the clinician's armamentarium in the assessment of these patients [1, 2]. Unfortunately, in the clinical setting more than one pathological process may be responsible for the impaired function, making it difficult to correlate the scan appearances with the pathology. In this study in rats we compared the renal DTPA scan appearances of the various pathological processes which may cause renal allograft dysfunction in the immediate post-transplant period. 相似文献
40.
Chronic food restriction has been shown to enhance glucose metabolism in adipocytes from lean Zucker rats at 10, 26, and 52 weeks of age compared to ad libitum-fed lean rats. Only adipocytes from food restricted 10-week-old obese rats demonstrated this response. In this study, lean and obese rats were food restricted from 5 until 14 weeks of age to determine the age at which adipocytes from obese rats were no longer affected by this intervention. Effects of 1 week of refeeding were also determined. When the rats were killed, body weights were highest in control rats followed by restricted/refed and then restricted rats within each genotype. Epididymal pad weights of lean rats were resistant to dietary intervention, while those of obese-restricted and obese-restricted/refed rats weighed less than pads of obese-control rats. Retroperitoneal pad weight was lowered by food restriction in both genotypes; but only that of lean-restricted/refed rats totally recovered with refeeding. Adipocytes of lean-restricted rats had the highest conversion of glucose to CO2. Glyceride-glycerol production was higher in obese compared to lean rats, but restricted rats had elevated conversion of glucose to fatty acids. In general, these results indicate that by 14 weeks of age obese Zucker rats no longer respond to food restriction with an elevated rate of glucose metabolism in adipocytes. 相似文献