间歇性腹膜透析治疗尿毒症脑病的疗效观察

目的 探讨间歇性腹膜透析对长期维持腹膜透析患者尿毒症脑病的治疗效果。方法 选择2013年1月-2018年12月本院肾内科长期维持腹膜透析出现尿毒症脑病患者46 例,并随机分为持续性不卧床腹膜透析(Continuous ambulatory peritoneal dialysis,CAPD)组及间歇性腹膜透析(Intermittent peritoneal dialysis,IPD)组,在治疗前及治疗7 d后分别采血进行血肌酐(Scr)、尿素氮(BUN)、甲状旁腺激素(iPTH)、白细胞介素6(IL-6)、β2微球蛋白(β2-MG)、超敏C反应蛋白(CRP)水平的检测,采用阳性与阴性症状量表评分表(PAN - SS)评价患者的疗效。结果 CAPD组治疗后血BUN、Scr、iPTH、IL-6、β2-MG、CRP水平与治疗前比较无明显变化(P>0.05); IPD组治疗后血BUN、Scr水平与治疗前比较无明显变化(P>0.05),而iPTH、IL-6、β2-MG、CRP水平较治疗前明显下降(P<0.05); 治疗后IPD组iPTH、IL-6、β2-MG、CRP水平与CAPD组比较有明显差异(P<0.05); PAN-SS显示,IPD组与CAPD组阳性症状、阴性症状、一般精神症状等方面均有明显差异(P<0.05); CAPD组无效8例,好转12例,显著进步4例,基本痊愈2例; IPD组无效2例,好转14例,显著进步5例,基本痊愈5例。结论 规律腹膜透析患者出现尿毒症脑病时应用间歇性腹膜透析治疗效果优于持续不卧床腹膜透析     

导尿管在动静脉内瘘阻塞重建中的临床应用

目的探讨外科手术联合导尿管取栓+扩张术用于治疗动静脉内瘘失功的优缺点,为治疗长期血液透析患者因内瘘血管狭窄导致血栓形成从而引起内瘘阻塞提供新的思路。方法选取因血栓形成导致前臂自体动静脉内瘘失功患者共36例纳入研究,在动静脉吻合口上方横行剪开已经动脉化的头静脉,应用导尿管逆行取栓并扩张近心端狭窄血管后吻合血管、缝合皮肤。分别观察手术临床成功率,应用超声测量术前、术后内瘘血管内径,并计算术后开通率,观察有无术后并发症等,共观察12个月。结果 34例患者术后均可触及明显震颤,术后第二天均应用内瘘进行血液透析,透析流量在200 mL/min以上,临床成功率为94.4%;血管狭窄部位的平均内径在手术前为(3.1±0.6) mm,术后为(4.5±0.8) mm,术后与术前相比较,差异有统计学意义(P0.05),经治疗后血管狭窄情况明显改善;K-M曲线分析其12个月时开放率为79.4%;36例患者术后均未出现严重并发症,仅2例出现肿胀手综合征,经治疗后症状消失。结论外科手术联合导尿管取栓+扩张的方式适用于部分动静脉内瘘闭塞的患者,尤其对于不能开展PTA等技术的基层医疗单位而言有其特殊的优势所在,具有一定的应用前景。     

活性氧介导醛固酮诱导的足细胞凋亡

目的 观察醛固酮（ALD）及其受体拮抗剂螺内酯（SPI）对足细胞活性氧（ROS）产生及凋亡的影响,并探讨其可能机制。 方法 体外培养条件的永生化小鼠足细胞系,分为空白对照组、ALD组、SPI组、ALD+SPI组;用荧光分光光度计检测足细胞内ROS水平;间接免疫荧光检测nephrin表达;流式细胞仪检测足细胞凋亡率;RT-PCR、Western 印迹法检测bax、bcl-2 mRNA及蛋白表达。同时观察抗氧化剂N-乙酰半胱氨酸（NAC）对上述效应的阻断作用。 结果 与对照组相比,ALD诱导足细胞ROS产生增多（P < 0.05）,该作用可被SPI阻断（P < 0.05）。ALD可诱导足细胞nephrin表达降低及足细胞凋亡（P < 0.05）,同时伴有bax mRNA、蛋白表达升高及bcl-2 mRNA、蛋白表达降低（P < 0.05）,SPI及NAC可阻断这一变化（P < 0.05）。 结论 ALD通过ROS途径作用于盐皮质激素受体上调促凋亡因子bax表达,下调抑凋亡因子bcl-2表达,进而诱导足细胞凋亡。     

双重滤过血浆置换疗法

双重滤过血浆置换(double filtration plasmapheresis,简称DFPP)系通过对一级分离后的致病血浆进行二级分离,然后将弃除致病因子后的血浆与血液有形成分一同输回体内,从而达到治疗疾病目的的一种选择性血浆分离疗法。DFPP是在膜式血浆分离技术上发展起来的新技术。1978年Mill w     

异体骨髓移植术后并发慢性移植物抗宿主病相关的膜性肾病一例

我们遇到1例慢性移植物抗宿主病（cGVHD）相关的膜性肾病，报道如下。 患者，男，15岁，1997年在本院诊断为急性淋巴细胞性白血病，于2004年4月在本院行异体骨髓移植术。术后给予甲泼尼龙（美卓乐）64mg／d及环孢素A5．6mg·kg^-1·d^-1口服，并逐渐减量。8个月后出现颜面及双下肢水肿、皮肤色斑、视物不清及尿蛋白3＋，诊断为cGVHD。     

TRPC6高表达对血管紧张素Ⅱ诱导的小鼠足细胞凋亡的影响

目的 观察瞬间受体电位阳离子通道蛋白6(TRPC6)高表达对血管紧张素Ⅱ(AnglI)诱导的小鼠足细胞凋亡的影响并探讨其作用机制.方法 用脂质体将针对小鼠TRPC6的基闪真核表达载体pEGFP.N1.mTRPC6转染体外培养的永生化小鼠足细胞系.24 h后用荧光显微镜观察增强绿色荧光蛋白(EGFP)的表达.Western印迹法检测转染后TRPC6蛋白表达的变化.将足细胞分组,应用不同浓度AngⅡ处理足细胞,Fluo-3AM结合激光共聚焦显微镜检测各组足细胞胞质内钙离子的浓度.RT-PCR及Westem印迹法检测Bax、Bcl-2 mRNA及蛋白的水平.流式细胞仪及Hoeehst染色法榆测足细胞凋亡.结果 pEGFP-NI-mTRPC6转染足细胞后,约35%细胞出现绿色荧光;足细胞TRPC6蛋白表达明显上调(P<0.01).TRPC6高表达町以明显促进AngII诱导的足细胞钙离子内流(P<0.01),在蛋白及基因水平均上调Bax的表达而下调Bcl.2的表达(P<0.01,P<0.05).在低剂量Ang Ⅱ(10-10mol/L)作用下.足细胞凋亡率为(2.50±0.72)%,转染TRPC6以后凋亡率为(4.33±0.45)%,差异有统计学意义(P<0.05).在高剂量Ang Ⅱ(10-6mol/L)作用下,足细胞凋亡率为(15.46±1.40)%.转染TRPC6以后凋亡率为(18.33±0.87)%,差异有统计学意义(P<0.01).结论 TRPC6在AngⅡ诱导的足细胞凋亡中发挥重要作用.TRPC6可能通过增加钙离子内流,进而启动其下游的捌亡调节成分参与凋亡过程.     

Protective effects of eplerenone on podocyte injury in adriamycin nephropathy rats

To investigate the protective effects of eplerenone on adriamycin-induced renal injury and the possible mechanisms involved,36 male Sprague-Dawley rats were randomly divided into control group,adriamycin nephropathy(AN) group and eplerenone-treated group(100 mg.kg-1.d-1 eplerenone).Blood pressure,24-h urinary protein,serum potassium,sodium and creatinine were measured 28 days after adriamycin injection(a single tail intravenous injection of 6.5 mg/kg adriamycin).The morphological changes of renal tissues were observed by light and electron microscopy.Immunohistochemistry and Western blotting were performed to examine the expression of TGF-β1 and desmin in renal cortex.The results showed that 28 days after adriamycin injection,there were no significant changes in the level of serum potassium,sodium,creatinine concentrations and blood pressure values in the rats of the three groups.Meanwhile,the 24-h proteinuria excretion in the AN group was significantly higher than that in the control group(P<0.01),but that in the eplerenone-treated group was substantially reduced when compared with that in the AN group(P<0.05).Mild mesangial cell proliferation and matrix expansion,diffuse deformation and confluence of foot processes in podocytes were found in the AN group.By contrast,rats in the eplerenone-treated group exhibited obvious attenuation of these morphological lesions.The protein expression of TGF-β1 and desmin in the AN group was markedly up-regulated in contrast to that in the control group(P<0.01),whereas that in the eplerenone-treated group was much lower than in the AN group(P<0.05).It was concluded that eplerenone may ameliorate the proteinuria and the development of pathological alteration in adriamycin-induced nephropathy presumably via the inhibition of cytokine release,and restore the morphology of podocytes independent of its blood pressure-lowing effects.     

Effect of down-regulation of TRPC6 on the puromycin aminonucleoside-induced apoptosis of mouse podocytes

Eukaryotic expression vectors carrying the small hairpin RNA （shRNA） for TRPC6 mRNA were constructed, and the effects of knocking-down TRPC6 on puromycin aminonucleoside （PAN）-induced apoptosis of mouse podocytes were observed. Two eukaryotic expression vectors containing small hairpin structure targeting TRPC6 named pGCsi-TRPC6A and pGCsi-TRPC6B were designed and synthesized. The plasmids were transfected into conditionally immortalized murine podocyte cell line by liposome. The changes in the TRPC6 mRNA and protein expression were observed by RT-PCR and Western blot after 48 h. Cultured podocytes were divided into four groups： control group, PAN treatment group, PAN treatment＋shRNA transfection group, and PAN treatment＋negative control group. The expression of Bax and Bcl-2 mRNA and proteins was detected by RT-PCR and Western-blot respectively. The apoptotic rate of podocytes was measured by flow cytometry. The results showed that the expression of TRPC6 mRNA and protein was decreased in the podocytes when transfected with pGCsi-TRPC6A, and pGCsi-TRPC6B. The expression of Bax was increased, and that of Bcl-2 was decreased at protein and mRNA levels in the podocytes after treated with PAN for 48 h. These changes was attenuated by knocking-down TRPC6. Knocking-down TRPC6 could effectively decrease the PAN-induced apoptosis of podocytes. It was concluded that TRPC6 may play an important role in the PAN-induced apoptosis of podocytes. Knocking-down TRPC6 gene could effectively prevent the podocytes from apoptosis induced by PAN.     

辛伐他汀对糖尿病大鼠肾脏的保护作用

目的观察辛伐他汀对糖尿病大鼠。肾脏TGF-β1、FN的调节作用。方法将雄性SD大鼠随机分为3组,健康对照组（C组）、糖尿病组（DM组）、辛伐他丁组（DM＋S组）,每组10只。用链脲佐菌素（STZ）制作糖尿病模型,DM＋S组于造模成功后给予辛伐他汀灌胃。8周末检测24小时尿蛋白排泄量、肾组织病理;免疫组化检测肾组织TGF-β1、FN的表达以及肾组织丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH—PX）活性的变化。结果辛伐他汀组大鼠24小时尿蛋白排泄量、肾小球平均面积、肾小球平均体积明显低于模型组;DM组大鼠肾脏TGF-β1、FN的表达明显高于C组和DM＋S组。模型组肾组织MDA含量明显高于对照组,而SOD、CAT、GSH—PX活性明显低于对照组,辛伐他汀可明显减轻这些变化。结论辛伐他汀可以降低糖尿病大鼠肾脏TGF-β1、FN的表达。     

TRPC6高表达对小鼠足细胞裂孔隔膜分子和细胞骨架的影响

瞬时受体电位阳离子通道蛋白6(TRPC6)是新近发现的联系足细胞裂孔隔膜与细胞骨架的重要分子,TRPC6功能异常在遗传性及获得性蛋白尿性肾小球疾病蛋白尿的发生、发展中起重要作用.