生脉注射液联合曲美他嗪治疗缺血性心肌病合并肾功能不全的临床疗效分析

目的:研究生脉注射液联合曲美他嗪治疗缺血性心肌病合并肾功能不全的临床疗效。方法:选取2015年3月至2017年3月我院收治的100例缺血性心肌病合并肾功能不全患者,按照随机数表法分为观察组(n=50)和对照组(n=50)。对照组采用曲美他嗪治疗,观察组采用生脉注射液联合曲美他嗪治疗。观察和比较两组的治疗疗效、治疗前后心功能指标(左心室射血分数(LVEF)、左室收缩末径(LVESD)、左室舒张末期内径(LVEDD))、肾功能指标(血肌酐(Scr),尿素氮(BUN))、心肌损伤标志物(血清胱抑素(Cys C)、同型半胱氨酸(HCY)、脑钠肽(BNP))水平的变化。结果:治疗后,观察组总有效率显著高于对照组[92.30%(48/52) vs.70.83%(34/48)](P0.05),LVEDD、LVESD水平均显著低于对照组[(51.21±8.54)mm vs.(56.63±10.83)mm,(42.91±6.30)mm vs.(45.86±7.32)mm](P0.05),LVEF水平均显著高于对照组[(46.02±7.85)%vs.(41.20±8.84)%](P0.05),Scr、BUN水平均显著低于对照组[(164.30±17.95)μmol/L vs.(211.75±19.31)μmol/L;(8.12±0.76)mmol/L vs.(11.74±1.72)mmol/L](P0.05)。血清Cys C、HCY、NT-Pro BNP水平均显著低于对照组[(0.90±0.21)mg/L vs 1.52±0.34)mg/L (12.34±3.89)μmol/L vs.(20.86±5.28)μmol/L,(298.47±78.41)ng/L vs.(402.35±92.76)ng/L](P0.05)。结论:生脉注射液联合曲美他嗪治疗缺血性心肌病合并肾功能不全的的临床疗效显著优于单用曲美他嗪治疗,其可有效改善患者心、肾功能,减轻心肌细胞损伤。     

肾衰宁胶囊联合血液透析对慢性肾功能衰竭患者肾功能及血液流变学的影响

目的:探讨肾衰宁胶囊联合血液透析对慢性肾功能衰竭患者肾功能及血液流变学的影响。方法:选取中国医科大学本溪中心医院于2015年1月-2017年9月期间收治的慢性肾功能衰竭患者80例为研究对象。根据随机数字表法将患者分为对照组(n=40)与研究组(n=40),两组患者均给予血液透析治疗,研究组在此基础上联合使用肾衰宁胶囊治疗,疗程均为3个月。观察并比较两组患者治疗3个月后临床疗效及不良反应发生情况,比较两组患者治疗前、治疗3个月后血肌酐(Scr)、尿素氮(BUN)、肾小球滤过率(eGFR)水平及全血高切黏度、全血低切黏度、血浆黏度、红细胞比容。结果:研究组患者总有效率为92.50%(37/40),高于对照组的67.50%(27/40),差异有统计学意义(P0.05)。两组患者治疗3个月后Scr、BUN水平较治疗前降低,且研究组低于对照组(P0.05);而两组患者治疗3个月后eGFR水平较治疗前升高,且研究组高于对照组(P0.05)。研究组患者治疗3个月后的全血高切黏度、全血低切黏度、血浆黏度以及红细胞比容均低于对照组(P0.05)。对照组不良反应发生率为7.50%,与研究组的10.00%比较差异无统计学意义(P0.05)。结论:肾衰宁胶囊联合血液透析对慢性肾功能衰竭患者有较好的治疗效果,能够改善患者肾功能状况,同时稳定患者血液流变学,并且安全性较好。     

超声对早期糖尿病肾病的诊断价值及肾动脉血流阻力指数与血清hs-CRP、VEGF的关系分析

目的:研究彩色多普勒超声对早期糖尿病肾病的诊断价值及肾动脉血流阻力指数与血清超敏C反应蛋白(hs-CRP)、血管内皮生长因子(VEGF)的关系。方法:选取从2017年2月～2018年2月兰州大学第二医院收治的早期糖尿病肾病患者50例记为病变组,另取同期于该院进行体检的健康人员50例记为对照组。分别对两组人员进行彩色多普勒超声检查,比较肾血流参数。采用酶联免疫吸附法检测两组人员血清hs-CRP、VEGF水平,并作指标间的相关性分析。结果:病变组肾主动脉、肾锥体两侧叶间动脉、肾段动脉的收缩期峰值速度、舒张期最低速度较对照组降低,病变组肾主动脉、肾锥体两侧叶间动脉、肾段动脉的阻力指数较对照组升高(均P0.05)。病变组血清hs-CRP、VEGF水平较对照组升高(均P0.05)。经Pearson相关性分析显示:早期糖尿病肾病患者肾主动脉、肾锥体两侧叶间动脉、肾段动脉的血流阻力指数与血清hs-CRP、VEGF均呈正相关关系(均P0.05)。结论:彩色多普勒超声应用于早期糖尿病肾病的诊断价值较高,且肾动脉血流阻力指数与血清hs-CRP、VEGF密切相关,临床工作中通过联合检测血清hs-CRP、VEGF,从而有助于早期糖尿病肾病的诊断。     

Urinary D-serine level as a predictive biomarker for deterioration of renal function in patients with atherosclerotic risk factors

Background: D-serine, the enantiomer of L-serine, was identified in mammals 20?years ago. Although a close relationship between D-serine and renal dysfunction has been shown, the clinical implications of urinary D- and L-serine in humans are poorly understood. The aim of this study was to evaluate the relationship between urinary D- and L-serine with well-known renal biomarkers, and clarify the prognostic value of D- and L-serine for renal events.

Methods: This cross-sectional, prospective study included 65 patients with atherosclerotic risk factors, who were followed up for a median of 16?months. The primary endpoint was a composite of end-stage renal disease and a decline in estimated glomerular filtration rate (eGFR)?≥?25% from baseline.

Results: Urinary D-serine concentrations showed a better correlation with eGFR than did urinary L-serine, whereas neither urinary D- nor L-serine correlated with tubular markers such as urinary liver-type fatty acid-binding protein and N-acetyl-beta-D-glucosaminidase. A Cox regression analysis revealed that low urinary D-serine levels were significantly associated with the primary endpoint after adjusting for confounding factors (hazard ratio 12.60; 95% confidence interval, 3.49–45.51).

Conclusions: Urinary D-serine is associated with glomerular filtration and can be a prognostic biomarker of renal dysfunction in patients with atherosclerotic risk factors.     

Modulating biochemical perturbations during 72-hour machine perfusion of kidneys: role of preservation solution

This study documents renal biochemistry during hypothermic machine perfusion of kidneys. It is intended to demonstrate that a comprehensive evaluation of organ viability during ex-vivo preservation is needed to increase the number of organs available for transplantation and to reduce the current renal discard rate. Porcine kidneys were hypothermically machine perfused for 72 h with either Unisol-UHK or Belzer-Machine Perfusion Solution, (Belzer-MPS). Renal perfusate samples were periodically collected and biochemically analyzed. Significant differences were measured in the renal metabolic activity between the two experimental groups while similar values for traditional parameters such as renal flow rate and vascular resistance values were recorded. The effluent of UHK perfused kidneys showed strong metabolites and NH(4)(+) dynamics (P<0.05 vs. baseline), while the Belzer-MPS kidneys metabolic activity led to little or no change of the effluent biochemistry relative to baseline.     

Iron chelation or anti-oxidants prevent renal cell damage in the rewarming phase after normoxic, but not hypoxic cold incubation

It has now been firmly established that, not only ischemia/reperfusion, but also cold itself causes damage during kidney transplantation. Iron chelators or anti-oxidants applied during the cold plus rewarming phase are able to prevent this damage. At present, it is unknown if these measures act only during the cold, or whether application during the rewarming phase also prevents damage. We aimed to study this after cold normoxic and hypoxic conditions. LLC-PK1 cells were incubated at 4 degrees C in Krebs-Henseleit buffer for 6 or 24h, followed by 18 or 6h rewarming, respectively. Cold preservation was performed under both normoxic (95% air/5% CO2) and hypoxic (95% N2/5% CO2) conditions. The iron chelator 2,2'-DPD (100 microM), anti-oxidants BHT (20 microM) or sibilinin (200 microM), and xanthine oxidase inhibitor allopurinol (100 microM) were added during either cold preservation plus rewarming, or rewarming alone. Cell damage was assessed by LDH release (n=3-9). Addition of 2,2'-DPD and BHT during cold hypoxia plus rewarming did, but during rewarming alone did not prevent cell damage. When added during rewarming after 6h cold normoxic incubation, BHT and 2,2'-DPD inhibited rewarming injury compared to control (p<0.05). Allopurinol did not prevent cell damage in any experimental set-up. Our data show that application of iron chelators or anti-oxidants during the rewarming phase protects cells after normoxic but not hypoxic incubation. Allopurinol had no effect. Since kidneys are hypoxic during transplantation, measures aimed at preventing cold-induced and rewarming injury should be taken during the cold.     

Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells

Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells.     

酸性成纤维细胞生长因子对庆大霉素和顺铂所致肾小管上皮细胞损伤的保护作用

目的:研究酸性成纤维细胞生长因子(aFGF)对庆大霉素(GM)和顺铂(DDP)引起的体外培养肾小管上皮细胞损害的保护作用。方法:大鼠肾皮质经研磨、过网、胰蛋白酶消化,进行肾小管上皮细胞的体外培养。经Cytokeratin 18抗体进行鉴定后,用GM、DDP建立损伤模型,观察aFGF对损伤的肾小管上皮细胞的保护作用。结果:①经形态学观察、GM或DDP组与对照组比较,CAT、SOD、GSH-Px、Na~ -K~ -ATP酶活性下降,而NAG活性和NO、MDA升高(P<0.01或P<0.05),提示肾小管上皮细胞的培养和GM、DDP损伤的建模成功。②aFGF GM或DDP组与GM组或DDP组比较,大多数生化和酶学指标有显著或非常显著性差异(P<0.05或P<0.01);而aFGF GM或DDP组与对照组比较,CAT、NAG、GSH-Px、Na~ -K~ -ATP酶活性无显著性差异,但SOD活性下降、NO、MDA升高尚有显著性差异(P<0.05)。结论:aFGF对GM、DDP损伤的肾小管上皮细胞有明显的保护作用。     

罗格列酮对果糖饲养SD大鼠肝肾功能、血脂、血常规的影响

目的:了解罗格列酮(Rosiglitazone)处理果糖饲养的SD大鼠后对肝、肾功能,血常规的影响。方法:将24只成年健康SD大鼠随机分为A、B两组。A组持续喂高果糖饲料1月后再随机分为:①高果糖饲养组;②果糖饲养同时用罗格列酮处理组。B组喂标准饲料1月后随机分为:①对照组;②罗格列酮处理组。采用氧化酶法、放免法等技术方法测定大鼠的空腹血糖、血脂、胰岛素水平,肝功能,肾功能,血常规等指标。结果:与对照组相比:果糖饲养组大鼠直接胆红素、总胆红素、间接胆红素、血糖、胰岛素、总胆固醇、甘油三酯等指标均升高;而总蛋白、钾、钠、氯、胰岛素敏感指数等指标均下降,差异均具有统计学意义(P＜0．05)。而罗格列酮处理组中总胆红素、间接胆红素、尿酸和尿素/肌酐等指标均升高;而总蛋白、球蛋白、钾、钠、氨水平、甘油三酯、血常规细胞数、血红蛋白均下降,差异具有统计学意义(P＜0．05)。与果糖饲养组相比,果糖饲养罗格列酮处理组的总胆红素、直接胆红素、谷草转氨酶、间接胆红素、谷丙转氨酶、总胆固醇均升高;而胰岛素、甘油三酯、钙离子水平均下降差异均具有统计学意义,且前面三个指标的差异更明显(P＜0．05)。结论:罗格列酮在治疗过程中虽改善了果糖饲养SD大鼠所引起的胰岛素抵抗,但会加重肝肾功能障碍;对机体有一定的毒副作用。     

氯沙坦联合螺内酯对预N-硝基-L-精氨酸甲酯诱导高血压模型大鼠肾脏纤维化及心室重塑的影响

摘要 目的：探讨氯沙坦联合螺内酯对预N-硝基-L-精氨酸甲酯（N''-nitro-L-arginine-methylesterhydrochloride,L-NAME）诱导高血压模型大鼠肾脏纤维化及心室重塑的影响。方法：选择8周龄Wistar大鼠为研究对象,通过给予0.1 %的L-NAME饮用水诱导高血压模型。将大鼠根据随机数字表法分为三组：对照组,诱导组和联合治疗组。通过超声心动图比较室间隔厚度和左心室后壁厚度。CODATM8无创血压系统监测大鼠心脏功能。通过蛋白印迹分析大鼠肾切片中I型胶原、III型胶原和CTGF的蛋白表达。Masson的三色染色评估肾脏组织胶原含量沉积。通过RT-PCR分析大鼠心脏肥大标志物和转录因子心房利钠肽（Atrial natriuretic peptide,ANP）和脑利钠肽（Brain natriuretic peptide,BNP）的表达。通过免疫组化和免疫比浊法分析大鼠肾小球硬化指数和白蛋白尿。结果：模型组较对照组大鼠室间隔厚度和左心室后壁厚度、MAP和心脏/体重比、I型胶原、III型胶原和CTGF的蛋白表达、ANP和BNP的mRNA表达、肾小球硬化指数和白蛋白尿以及SMA和TGF-β1的蛋白表达均显著增加,FS显著降低（P<0.05）,联合治疗组较模型组室间隔厚度和左心室后壁厚度、MAP和心脏/体重比、I型胶原、III型胶原和CTGF的蛋白表达、ANP和BNP的mRNA表达、肾小球硬化指数和白蛋白尿以及SMA和TGF-β1的蛋白表达均显著降低,FS显著增加（P<0.05）。结论：氯沙坦联合螺内酯可减轻L-NAME诱导的高血压大鼠模型中心脏重塑和肾脏纤维化的发生。