环孢素A药物质量浓度监测对患者早期移植肾功能的影响

目的:通过监测环孢素A的血药质量浓度,来判断和调整肾移植术后服用环孢素A(CsA)的有效剂量,为临床减少并发症提供参考.方法:采用免疫荧光偏振TDX法,测定286例肾移植术后受者全血CsA质量浓度,其中164例监测CsA谷值质量浓度(Co组),122例监测CsA峰值质量浓度(C2组).计算各自的药代动力学参数,分析两组CsA质量浓度测定值与肾移植功能状况及相关临床资料的关系.结果:两组出现急性排斥反应的发生率,Co组明显高于C2组,两组存在显著差异(P＞0.05),但两组在药物性肝、肾中毒及肺感染的发生率方面比较均未见显著差异(P＜0.05).结论:对CsA峰值质量浓度进行药代动力学的监测,可以较准确反映肾移植受者的药物剂量,尤其在监控急性排斥反应方面意义较大,同时也可减少CsA肾中毒的危险.     

3Rs原则的应用实例——用鸡胚肝细胞替代鸡肾细胞培养禽腺病毒

在动物实验中利用减少 (reduction)、替代 (replacement)和优化 (refinement)的 3Rs原则 ,是执行实验动物福利的重要体现。利用SPF鸡胚肝细胞培养禽腺病毒 ,用于制备诊断抗原和病毒研究 ,取代用SPF鸡肾细胞培养禽腺病毒 ,通过观察细胞病变和测定抗原滴度分析比较 ,前者完全可以替代后者制备禽腺病毒诊断抗原 ,是利用 3Rs原则的具体实践。尽可能利用可替代实验动物的替代物 ,通过细胞组织培养的方法取代活体动物进行实验 ,将动物的痛苦减至最低     

LC3真核表达载体构建及其在293T细胞中自噬诱导研究

【目的】构建pEGFP-N1-LC3真核表达载体,并将其转染进人胚肾细胞293T,通过Earle's盐平衡液(Balanced salt solution,EBSS)饥饿诱导观察细胞自噬现象。【方法】RT-PCR扩增LC3基因,并将其插入pEGFP-N1真核表达载体构建重组质粒。将重组质粒转染至人胚肾细胞293T,显微镜观察、Western blot检测GFP-LC3融合蛋白表达情况。对转染细胞进行Earle's盐平衡液饥饿诱导,通过Western blot验证自噬指标,激光共聚焦显微镜观察自噬泡形成。【结果】成功构建pEGFP-N1-LC3真核表达载体,并在293T细胞中成功表达目的蛋白,在进行Earle's盐平衡液饥饿诱导后观察到自噬泡的形成,Western blot检测到LC3-Ⅰ向LC3-Ⅱ的转化。【结论】本实验为研究自噬在癌细胞病理进程中的机制提供了实验素材。     

双酚类化合物对人胚肾细胞HEK293的毒性和氧化应激的研究

双酚类化合物(bisphenols, BPs)是一类新型环境有机污染物,BPs排放到环境介质后经多种途径进入生物体并在体内蓄积,已逐渐成为威胁环境和健康的重要风险因子。为探明BPs对人体健康的潜在毒性效应,本研究选取人胚肾细胞HEK293作为模型,通过测定细胞活力、胞内活性氧含量、氧化应激参数(SOD、GSH、MDA)及细胞内钙离子水平,比较了BPA、BPS、BPF和BPAF对HEK293细胞的毒性影响。结果表明,BPA、BPS、BPF和BPAF能够不同程度的抑制HEK293细胞活力,通过促进氧化应激产生 ROS,降低抗氧化能力,迅速提高细胞内Ca²⁺水平,诱导HEK293细胞损伤。在本研究所选的浓度范围内,BPAF对HEK293细胞的毒性影响最大,BPA和BPF对HEK293细胞的毒性影响次之,BPS对HEK293细胞的毒性影响较小。本研究为深化了解双酚类化合物的毒理学系统研究和风险评估提供参考依据。     

瑞舒伐他汀对大鼠造影剂急性肾损伤的保护作用及机制

通过建立大鼠非离子低渗型造影剂急性肾损伤模型,探讨瑞舒伐他汀对大鼠非离子低渗型造影剂急性肾损伤的保护作用及机制。将36只健康成年SD大鼠随机分组:正常对照组(NS组);造影剂对照组(CM组);瑞舒伐他汀干预组(RV组)。RV组于注射造影剂前12 h按10 mg/kg瑞舒伐他汀混悬液灌胃,NS组、CM组灌胃等量生理盐水。CM组、RV组以10m L/kg剂量行大鼠尾静脉注射造影剂(优维显370,370 mg I/m L),NS组注射等量的生理盐水,分别在造影24 h和72 h后取材。使用苏木精-伊红(HE)染色法,观察肾小管的病理形态学变化。测定血清胱抑素C(Cys-C)、血清肌酐(Scr)、尿α1-微球蛋白(α1-MG)、尿微量白蛋白(m ALB)、尿N-乙酰-B-D-葡萄糖酸苷酶(NAG)水平,以评估大鼠肾脏功能变化。测定血清超敏C反应蛋白(Hs-CRP)以及肾组织中超氧化物歧化酶(SOD)活性,以评估炎症和氧化应激反应。结果表明:1与CM组大鼠相比给予瑞舒伐他汀治疗能明显减轻大鼠肾脏损伤程度;2 CM组和RV组大鼠血Scr、血Cys-C、尿NAG、尿α1-MG、尿m ALB均较NS组显著升高,给予瑞舒伐他汀治疗组大鼠与CM组大鼠相比,上述各项指标均显著下降(p0.05);组内比较,CM组大鼠上述各项指标72 h较24 h上升显著(p0.05),其余各组无明显差异(p0.05);3 CM组和RV组大鼠血清Hs-CRP水平均较NS组明显升高,RV组较CM组血清Hs-CRP降低显著(p0.01);组内血清Hs-CRP比较,CM组大鼠随时间升高明显(CM 24 h vs CM 72 h,p0.05),给予瑞舒伐他汀治疗组大鼠则明显下降(RV 24 h vs RV 72 h,p0.05);4CM组和RV组大鼠肾组织SOD活性均较NS组明显降低,RV组与CM组相比SOD活性显著升高(p0.01);组内比较,CM组大鼠肾组织SOD活性随时间降低明显(CM 24 h vs CM 72 h,p0.05),而RV组大鼠肾组织SOD活性随时间显著升高(RV 24 h vs RV 72 h,p0.05)。说明短期瑞舒伐他汀干预通过降低血浆细胞炎症因子水平、降低造影剂肾病大鼠肾脏氧化应激水平,减轻造影剂肾病大鼠肾脏的损伤程度,对造影剂肾病大鼠具有一定程度的保护作用。     

Renal vascular reactivity to ATP in hyper- and hypothyroid rats

The effects of adenosine triphosphate (ATP) on the renal vasculature of isolated kidneys from control, hyper- and hypothyroid rats were characterized. ATP responsiveness was evaluated in basal tone and in raised tone (phenylephrine 10^–6 M) preparations. These responses were compared with those obtained with barium chloride or sodium nitroprusside (SNP), used respectively as nonreceptor agonists for vasoconstriction or vasodilation. In preparations at basal tone, ATP produced dose-related vasoconstriction, which was increased in hyperthyroid kidneys, and was severely attenuated in kidneys from hypothyroid rats. In raised tone preparations from control rats ATP produced a dual response: vasoconstriction at low doses, which declined with increasing doses to give way to vasodilator responses; biphasic responses were found in some kidneys. Hyperthroid kidneys showed increased pressor responses and a vasodilator response similar to those seen in kidneys from control rats. However, in hypothyroid kidneys the vasodilator response was abolished. The responses to barium chloride and to SNP were significantly increased and decreased in hyper- and hypothyroid kidneys, respectively; vasoconstrictor responses to SNP were also found in hypothyroid kidneys. Hence the abnormal responses to ATP observed in both thyroid dysfunctions may be partially explained by unspecific alterations in the contractile machinery of the renal vasculature in these kidneys. However, ATP responsiveness (vasoconstriction at low tone and vasodilation at raised tone) was more severely affected in hypothyroid kidneys, suggesting that purinergic (P_2X and P_2Y) receptor activity may be decreased in these organs.     

Induction of the synthesis of thymidine kinase by aldosterone in the kidney of the immature male rat

Summary Thymidine kinase activity was studied in kidneys from immature male rats after administration of aldosterone. Kinetic studies showed that the enzyme activity reached its maximum level 24 h after aldosterone injection. That increase was specific for aldosterone and could be related to the synthesis of new molecules of enzyme.     

纤维素-DMSO-PF浓溶液的粘弹性及其膜的研制和应用

把纤维素直接溶于二甲基亚砜(DMSO)和多聚甲醛(PF)中,能制成可纺性良好的纤维素浓溶液。测定其流变性能,首次直接得到纤维素浓溶液的粘流活化能等物理参数。以往这些物理参数都是间接地从纤维素酯、醚类的浓溶液获得,其准确性受酯、醚化条件的限制。我们研究了热力学和动力学条件与原液可纺性之间关系,获得最佳可纺性原液的热力学和动力学参数。在此基础上探讨了纤维素中空纤维膜的成形理论和成形工艺,首先用有机溶剂法纺制出纤维素中空纤维膜。调节原液条件和成形工艺参数,可在一定范围内调整中空纤维膜的透析能力。用溶剂法纤维素中空纤维膜组装成的人工肾透析器,具有良好的透析能力,能把血液中的低分子部分如尿素、肌肝等排出体外,而有用物质如B_(12)等则大部分保留,高分子部分如蛋白质、血球等则安全保留在血液中。经医院测定可在临床上进行应用。     

海绵肾(附2例报告及文献复习)

本文报告二例海绵肾,第一例因对它的特征性病变认识不足,误诊为多发性肾结石而进行了不必要的手术。另一例经保守治疗,恢复良好。本文结合国内外文献,对海绵肾的发病率、病理、临床症状和治疗作了讨论。对海绵肾的诊断主要根据尿路平片和高浓度大剂量排泄性尿路造影,能显示一种特征性的X线表现。现代治疗,除合并症以外保守疗法为主。     

Control of the cardiovascular system ofAplysia by identified neurons

The neural network that controls the cardiovascular system ofAplysia adapts cardiovascular function to a variety of different physiological and behavioral situations. It (1) coordinates the cardiovascular system with the renal and respiratory systems; (2) modifies both systemic and regional blood flow during food-elicited arousal and feeding; and (3) changes the tension of longitudinal vascular muscle to adapt the arterial tree to changes in body shape. Indirect evidence suggests that the cardiovascular control circuit may also play a role in maintaining homeostasis during egg laying. Several putative neurotransmitters, including acetylcholine, serotonin, R151 and R152 peptides, have been localized to identified neurons in this circuit.