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91.
Relaxin down-regulates renal fibroblast function and promotes matrix remodelling in vitro. 总被引:1,自引:0,他引:1
Rosemary Masterson Tim D Hewitson Kristen Kelynack Marina Martic Laura Parry Ross Bathgate Ian Darby Gavin Becker 《Nephrology, dialysis, transplantation》2004,19(3):544-552
BACKGROUND: Renal fibroblasts are important effector cells in tubulointerstitial fibrosis, with experimental antifibrotic strategies focusing on the functional down-regulation of these cells. Several experimental models of fibrosis have provided evidence for the effectiveness of the polypeptide hormone relaxin as a potential antifibrotic agent. This study was conducted to further elucidate the antifibrotic mechanisms of relaxin on renal fibroblasts in vitro. METHODS: Rat cortical fibroblasts were obtained from outgrowth culture of renal tissue isolated from kidneys 3 days post-unilateral ureteric obstruction and constituted 100% of cells studied. A relaxin radio-receptor assay was used to establish binding of relaxin to renal fibroblasts in vitro. Functional studies then examined the effects of H2 relaxin (0, 1, 10 and 100 ng/ml) on fibroblast kinetics, expression of alpha-smooth muscle actin (alpha-SMA), total collagen synthesis, collagenase production and collagen-I lattice contraction. CTGF mRNA expression was also measured by northern analysis. RESULTS: H2 relaxin bound with high affinity to rat renal fibroblasts, but receptor numbers were low. Consistent with its previously reported bimodal effect, transforming growth factor (TGF-beta 1) reduced fibroblast proliferation, an effect abrogated by H2 relaxin. Fibroblasts exposed to H2 relaxin (100 ng/ml) for 24 h demonstrated decreased immunostaining for alpha-SMA and reduced alpha-SMA protein expression compared with controls. There was a trend for a relaxin-mediated reduction in total collagen synthesis and alpha 1(I) mRNA expression with large dose-related increases in collagenase protein expression being observed. TGF-beta 1-stimulated collagen-I lattice contraction was significantly inhibited following co-incubation with 100 ng/ml relaxin. Incremental doses of H2 relaxin had no significant effect on CTGF mRNA expression. CONCLUSIONS: The findings of this study suggest that the antifibrotic effects of relaxin involve down-regulation of fibroblast activity, increase in collagenase synthesis and restructuring of collagen-I lattices, which are consistent with its known physiological role of matrix remodelling. Although there appears to be an interaction between TGF-beta 1 and H2 relaxin, this does not appear to involve a reduction in CTGF mRNA expression. 相似文献
92.
Alfred Philip James Lake BSc MBBS FFARCS ; Kathiravelpillai Puvanachandra MBBS DO FRCS FRCOphth 《Pain practice》2004,4(2):130-131
Abstract: Stellate ganglion block is commonly used to treat the sympathetically maintained pain which may occur in one‐third of patients with complex regional pain syndrome type 1. A complication that followed a single block and presented a diagnostic dilemma for the ophthalmologist is reported. 相似文献
93.
目的:观察核心结合因子a1(Cbfa1)对兔骨髓间充质干细胞(MSCs)向成骨细胞分化的诱导作用。方法:体外分离培养兔骨髓MSCs,用AdEasy1/Cbfa1。转染MSCs,在转染后3d,1、2、3和4周时,组织化学和免疫组化等方法检测成骨标志碱性磷酸酶和骨钙素的表达。结果:AdEasy1/Cbfa1转染后的兔骨髓MSCs表现出与成骨细胞相似的形态,并且表达碱性磷酸酶和骨钙素。结论:Cbfa1可诱导兔骨髓MSCs向成骨细胞分化。 相似文献
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95.
F Celi V Bini F Papi E Santilli M S Castellani A Ferretti M Mencacci M G Berioli G De Giorgi A Falorni 《Diabetic medicine》2006,23(6):660-665
AIM: To determine the influence of Type 1 diabetes mellitus on circulating adipocytokines in children. METHODS: The circulating concentrations of leptin, adiponectin, resistin and tumour necrosis factor (TNF)-alpha were measured in 91 children, aged 11.1 +/- 2.7 years, with Type 1 diabetes mellitus (T1DM). Ninety-one healthy children were selected as control subjects. RESULTS: Body mass index-adjusted leptin concentrations were higher in the pubertal diabetic children compared with the control children. There was a significant positive correlation between leptin and daily insulin dose in the diabetic group. Circulating adiponectin concentrations were higher in the prepubertal diabetic children and were positively associated with HbA(1c). Resistin concentrations were lower in the prepubertal non-diabetic subjects compared with the pubertal non-diabetic children, whose values were higher than those of the diabetic children. TNF-alpha concentrations were similar in non-diabetic and diabetic children. CONCLUSIONS: Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations. 相似文献
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99.
静脉预注H1,H2受体阻滞药对减轻鱼精蛋白副作用的研究 总被引:3,自引:0,他引:3
将30例ASD、VSD患者随机分为对照与预防用药两组,对比观察H1、H2受体阻滞药苯海拉明、西米替丁对减轻鱼精蛋白副作用的效果和应用鱼精蛋白后补体C3、C4、CH50浓度变化。结果发现预防用药组血液动力学变化明显小于对照组,两组之间差异显著(P<0.01)。应用鱼精蛋白后C3、C4、CH50均下降,与用药前相比差异显著(P<0.01)。提示鱼精蛋白中和肝素可引起补体激活、组胺释放,H1、H2受体阻滞药能够减轻鱼精蛋白引起的血压下降。 相似文献
100.
The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase
activity is responsible for both therapeutic and side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacological
results with developmental compounds suggest that COX-2 is the relevant target for the therapeutic (i.e. anti-inflammatory)
effects of NSAIDs, whereas gastric and renal side-effects are related to inhibition of constitutive COX-1. However a role
of COX-1 in inflammation cannot be excluded. Furthermore, more research effort is needed to investigate the functional relevance
of COX-2 in normal tissue. 相似文献