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41.
42.
以D-氨基半乳糖(D-Galactosamine,D-GalN)造成急性肝损伤(急性肝炎、急性肝坏死)大鼠模型后、对照观察了急性肝损伤大鼠血浆氨基酸的变化,建立了大鼠急性肝损伤时血浆氨基酸的变化模式并对其发生机理进行了探讨。大鼠血浆氨基酸的测定采用聚酰薄层荧光分析技术,其测定结果是:急性肝炎组,酪氨酸(Tyr)、天冬氨酸(Asp)、谷氨酰胺(Gln)和鸟氨酸(Orn)升高,精氨酸(Arg)下降,其余氨基酸无显著变化。急性肝坏死组,除Arg显著下降外,其余所有氨基酸都显著升高,而两组支链氨基酸(BCAA)/芳香族氨基酸(AAA)克分子比值均显著下降。 相似文献
43.
Ian G. Town Gary J. Phillips Edile Murdoch Stephen T. Holgate Frank J. Kelly 《Free radical research》1993,18(4):211-221
The time course and nature of the pulmonary inflammatory and antioxidant responses, both during and after hyperoxic-induced acute lung injury were studied in the preterm guinea pig. Three-day preterm (65 days gestation) guinea pigs were randomly exposed to either 21% O2 (control) or 95% O2 (hyperoxia) for 72 hours. All pups were then maintained in ambient conditions for up to a further 11 days, during which time lung damage was monitored. In animals exposed to hyperoxia, evidence of acute lung injury and inflammation was characterized by a marked increase in microvascular permeability and elevated numbers of neutrophils in bronchoalveolar lavage fluid. Protein concentration, elastase-like activity and elastase-inhibitory capacity in lavage fluid were at a maximum at the end of the 72 hours hyperoxic exposure. Four days later, all values had returned to control levels. In contrast, increased numbers of neutrophils, macrophages and lymphocytes were recovered in the lavage fluid during this early recovery period. Coinciding with the influx of inflammatory cells, there was a significant increase in glutathione peroxidase, manganese superoxide dismutase and catalase activities in immature lung. Lung copper/zinc superoxide dismutase activity remained unchanged during both experimental periods. The strong temporal relationship between the influx of inflammatory cells to the lung and the induction of pulmonary antioxidant enzyme defences suggests that a common mechanism underlies both responses. These findings have led us to regard inflammation in the hyperoxic-injured immature lung as a beneficial event and not, as previously suggested, as part of the injurious process. 相似文献
44.
Takenobu Ishii Montserrat Ruiz-Torruella Jae Young Kim Hiroyuki Kanzaki Abdullah Albassam Wichaya Wisitrasameewong Satoru Shindo Roodelyne Pierrelus Alireza Heidari Umadevi Kandalam Shin Nakamura Alexandru Movila Dmitriy Minond Toshihisa Kawai 《Journal of cellular and molecular medicine》2023,27(12):1750-1756
Bone remodelling is mediated by orchestrated communication between osteoclasts and osteoblasts which, in part, is regulated by coupling and anti-coupling factors. Amongst formally known anti-coupling factors, Semaphorin 4D (Sema4D), produced by osteoclasts, plays a key role in downmodulating osteoblastogenesis. Sema4D is produced in both membrane-bound and soluble forms; however, the mechanism responsible for producing sSema4D from osteoclasts is unknown. Sema4D, TACE and MT1-MMP are all expressed on the surface of RANKL-primed osteoclast precursors. However, only Sema4D and TACE were colocalized, not Sema4D and MT1-MMP. When TACE and MT1-MMP were either chemically inhibited or suppressed by siRNA, TACE was found to be more engaged in shedding Sema4D. Anti-TACE-mAb inhibited sSema4D release from osteoclast precursors by ~90%. Supernatant collected from osteoclast precursors (OC-sup) suppressed osteoblastogenesis from MC3T3-E1 cells, as measured by alkaline phosphatase activity, but OC-sup harvested from the osteoclast precursors treated with anti-TACE-mAb restored osteoblastogenesis activity in a manner that compensates for diminished sSema4D. Finally, systemic administration of anti-TACE-mAb downregulated the generation of sSema4D in the mouse model of critical-sized bone defect, whereas local injection of recombinant sSema4D to anti-TACE-mAb-treated defect upregulated local osteoblastogenesis. Therefore, a novel pathway is proposed whereby TACE-mediated shedding of Sema4D expressed on the osteoclast precursors generates functionally active sSema4D to suppress osteoblastogenesis. 相似文献
45.
46.
摘要 目的:探讨尿铜蓝蛋白(CP)、肾损伤因子1(KIM-1)与糖尿病肾病(DKD)患者肾功能的关系及对预后不良的预测价值。方法:回顾性分析2017年1月~2019年1月陆军第八十二集团军医院肾内科收治的160例DKD患者(DKD组)的临床资料,随访3年,根据是否发展为终末期肾脏疾病(ESRD)分为预后不良组42例和预后良好组118例,另选取同期56例单纯2型糖尿病(T2DM)患者作为T2DM组和47例体检健康者作为对照组。采用微量法和酶联免疫吸附试验法检测尿CP、KIM-1水平,并计算尿白蛋白/肌酐比值(UACR)和估算肾小球滤过率(eGFR)。通过Spearman相关性分析DKD患者尿CP、KIM-1与UACR、eGFR的相关性,单因素和多因素Logistic回归分析DKD患者预后不良的影响因素,受试者工作特征(ROC)曲线分析尿CP、KIM-1对DKD患者预后不良的预测价值。结果:随访3年,160例DKD患者有42例发展为ESRD,预后不良发生率为26.25%(42/160)。DKD组尿CP、KIM-1、UACR高于T2DM组、对照组,eGFR低于T2DM组、对照组(P<0.05);T2DM组尿CP、KIM-1、UACR高于对照组,eGFR低于对照组(P<0.05)。Spearman相关性分析显示,DKD患者尿CP、KIM-1与UACR呈正相关(P均<0.001),与eGFR呈负相关(P均<0.001)。多因素Logistic回归分析显示,高血压、DKD分期4期和糖化血红蛋白(HbA1c)(较高)、低密度脂蛋白胆固醇(LDL-C)(较高)、UACR(较高)、尿CP(较高)、尿KIM-1(较高)为DKD患者预后不良的独立危险因素(P<0.05),eGFR(较高)为独立保护因素(P<0.05)。ROC曲线分析显示,尿CP、KIM-1联合预测DKD患者预后不良的曲线下面积大于各指标单独预测。结论:DKD患者尿CP、KIM-1升高与肾功能降低和预后不良密切相关,尿CP、KIM-1联合预测DKD患者预后不良的价值较高。 相似文献
47.
摘要 目的:分析铜蓝蛋白(CER)、鳞状细胞癌相关抗原(SCCA)与慢性肾功能衰竭的关系及对病情进展的预测价值。方法:选择我院自2019年4月至2021年4月接诊的169例慢性肾功能衰竭患者作为研究对象,根据24 h尿白蛋白定量分为微量白蛋白尿组(<200 mg/24 h,102例)和大量白蛋白尿组(>200 mg/24 h,67例)。比较两组各项实验室指标及血清CER、SCCA水平,分析CER、SCCA与慢性肾功能衰竭患者肾功能指标的关系。随访12个月,观察病情进展,使用受试者工作特征曲线(ROC)评价血清CER联合SCCA对病情进展的预测效能。结果:大量白蛋白尿组血清肌酐(Scr)、血尿素氮(BUN)水平均明显高于微量白蛋白尿组,肾小球滤过率(GFR)低于微量白蛋白尿组(P<0.05);大量白蛋白尿组血清CER、SCCA水平均高于微量白蛋白尿组(P<0.05);经Pearson相关性分析,慢性肾功能衰竭患者血清CER、SCCA水平均与Scr、BUN呈正相关,与GFR呈负相关(P<0.05);经多因素Logistic回归分析,GFR、CER、SCCA均是慢性肾功能衰竭患者病情进展的独立预测因素(P<0.05);经ROC曲线分析,血清CER联合SCCA预测慢性肾功能衰竭患者病情进展的AUC为0.925,明显大于GFR的0.620(P<0.05)。结论:血清CER、SCCA水平与慢性肾功能衰竭患者肾功能呈负相关,联合预测病情进展效能较好,值得临床予以重视应用。 相似文献
48.
摘要 目的:探讨三七总皂苷联合顺铂对胃癌大鼠肾损伤的改善作用并分析潜在机制。方法:选择60只健康SD雄性大鼠分为对照组、胃癌模型组、顺铂组及三七总皂苷组,各15只。除对照组外,其余组大鼠采用皮下接种胃癌BGC823细胞悬液法建立胃癌模型。建模成功后,给予对照组和胃癌模型组大鼠生理盐水腹腔注射和灌胃,给予顺铂组大鼠腹腔注射25 mg/kg顺铂注射液并灌胃生理盐水,给予三七总皂苷组大鼠腹腔注射25 mg/kg顺铂注射液并灌胃30 mg/kg三七总皂苷。分别于建模成功时、药物处理28 d时采用酶联免疫吸附法检测血清肌酐(SCr)、尿素氮(BUN)和尿液β-N-乙酰氨基葡萄糖苷酶(NAG)、肾损伤分子1(KIM-1)水平。处死大鼠后取肾脏,分别测定肾脏组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、谷胱甘肽(GSH)水平,制备肾脏组织石蜡切片并行苏木精-伊红染色后观察大鼠肾组织的病理学变化。采用TUNEL染色法检测肾脏组织细胞凋亡情况,采用Western Blotting法检测肾脏组织中LC3、HIF-1α和Beclin1 蛋白表达情况。结果:顺铂组和三七总皂苷组大鼠血清SCr、BUN和尿液NAG、KIM-1水平均显著高于对照组和模型组(P<0.05),三七总皂苷组大鼠血清SCr、BUN和尿液NAG、KIM-1水平显著高于顺铂组(P<0.05)。三七总皂苷组大鼠肾脏组织SOD、GSH水平显著低于模型组但显著高于顺铂组,MDA显著高于模型组但显著低于顺铂组(P<0.05),CAT与模型组无显著差异(P<0.05),但显著高于顺铂组(P>0.05)。顺铂组大鼠肾小管明显扩张、管腔狭窄,基底层上皮细胞水肿、坏死并形成空泡,肾小管。三七总皂苷组大鼠肾脏病理学改变程度显著轻于顺铂组。顺铂组和三七总皂苷组大鼠肾脏组织细胞凋亡指数显著增加,三七总皂苷组大鼠肾脏组织细胞凋亡指数显著低于顺铂组(P<0.05)。顺铂组大鼠肾脏组织中LC3、HIF-1α和Beclin1蛋白水平均显著高于模型组,但显著低于三七总皂苷组(P<0.05)。结论:三七总皂苷可能通过减轻过氧自由基和过氧化水平、增强线粒体自噬水平减少肾组织细胞凋亡,减轻顺铂引起的胃癌大鼠肾损伤。 相似文献
49.
Gerald A. Klassen David Janigan Barry Paton John Mathews Bernard Perey Allan S. Macdonald Katherine D. Barclay 《Obesity (Silver Spring, Md.)》1996,4(2):145-151
Objective: To measure red cell flux of adipose tissue in morbidly obese patients' pannus in the upright and supine position to determine factors which would render the lower pannus susceptible to ischemic necrosis. Design: A cohort study of morbidly obese subjects without ischemic necrosis. Setting: University teaching hospital. Patients: Twenty-three consecutive morbidly obese patients referred for gastroplasty. Measurements: Red cell flux, measured as RMS voltage by a laser Doppler velocimeter. An optical fiber with a tip diameter of 250μ was inserted into the upper and lower pannus and output recorded in the upright and supine positions. Other variables recorded were age, BMI, blood pressure and serum lipids. Results: Adipose tissue red cell flux demonstrates considerable spatial and temporal heterogeneity from subject to subject and in various locations in the pannus. No differences in red cell flux were detected in response to change in position. However, regression analysis demonstrated that the gradient between the upper and lower abdomen in the supine position was increasingly positive with age and in the upright position it was increasingly positive with increasing weight or BMI. Conclusions: These data suggest that red cell flux is heterogeneously distributed in the abdominal pannus and is not greatly influenced by body position. However, with increasing age and adiposity there is a gradient for decreased red cell flux to the lower portion of the pannus. This may be a factor in rendering this part of the pannus prone to ischemic fat necrosis. 相似文献
50.
Post-translational modifications are fundamental to processes controlling behaviour, including cellular signaling, growth and transformation. As the molecular basis of protein modifications in normal and disease processes are becoming better defined, so new strategies for designing therapeutic entities to control complex disease processes are emerging. 相似文献