比较L-精氨酸、肌苷对肾脏功能保护的实验研究

探讨L-精氨酸(L-Arg)的肾功能保护作用机制及与肌苷的疗效比较。模拟手术肾损伤模型,分别采用放射免疫法和硝酸还原酶法检测手术前后大鼠不同时期尿液β2-MG、血浆NO含量变化。结果表明L-Arg和肌苷均对肾功能损伤有明显保护作用,L-Arg比肌苷更快地促进肾功能的恢复。     

Effects of Renal Denervation on Renal Artery Function in Humans: Preliminary Study

Aim

To study the effects of RD on renal artery wall function non-invasively using magnetic resonance.

Methods and Results

32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble®). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders.

Conclusions

RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress.     

Effects of Acute Sodium Fluoride Exposure on Kidney Function, Water Homeostasis, and Renal Handling of Calcium and Inorganic Phosphate

Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver and kidney. In this study, we performed an early analysis of renal function using a clearance technique in Wistar rats acutely exposed to fluoride at a plasma concentration of 0.625 μg/ml. Our results revealed that fluoride, at a concentration close to the concentration present in the serum after environmental exposure, induced a significant tubular dysfunction, resulting in diluted urine, impaired protein reabsorption, and increased calcium and phosphate urinary excretion. Our work demonstrates that even acute exposures to low concentrations of NaF may induce renal damage and confirms that, after exposure, the kidney participates directly in the calcium and phosphate deficiencies observed in fluoride-exposed populations.     

硫酸粘菌素对碱性磷酸酶部分性质的影响

硫酸粘菌素对碱性磷酸酶有抑制作用,用Dixon作图求出抑制常数为Ki=4.88×10-6mol/L,抑制类型为非竞争性抑制.通过紫外吸收光谱,发现硫酸粘菌素引起碱性磷酸酶的空间结构发生改变;由荧光光谱变化,发现硫酸粘菌素对碱性磷酸酶有荧光淬灭作用,淬灭机理是因能量转移而引起的静态淬灭.     

Sodium Thiosulfate Ameliorates Oxidative Stress and Preserves Renal Function in Hyperoxaluric Rats

Background

Hyperoxaluria causes crystal deposition in the kidney, which leads to oxidative stress and to injury and damage of the renal epithelium. Sodium thiosulfate (STS, Na₂S₂O₃) is an anti-oxidant, which has been used in human medicine for decades. The effect of STS on hyperoxaluria-induced renal damage is not known.

Methods

Hyperoxaluria and renal injury were induced in healthy male Wistar rats by chronic exposure to ethylene glycol (EG, 0.75%) in the drinking water for 4 weeks. The treatment effects of STS, NaCl or Na₂SO₄ were compared. Furthermore, the effects of STS on oxalate-induced oxidative stress were investigated in vitro in renal LLC-PK1 cells.

Results

Chronic EG exposure led to hyperoxaluria, oxidative stress, calcium oxalate crystalluria and crystal deposition in the kidneys. Whereas all tested compounds significantly reduced crystal load, only STS-treatment maintained tissue superoxide dismutase activity and urine 8-isoprostaglandin levels in vivo and preserved renal function. In in vitro studies, STS showed the ability to scavenge oxalate-induced ROS accumulation dose dependently, reduced cell-released hydrogen peroxide and preserved superoxide dismutase activity. As a mechanism explaining this finding, STS was able to directly inactivate hydrogen peroxide in cell-free experiments.

Conclusions

STS is an antioxidant, which preserves renal function in a chronic EG rat model. Its therapeutic use in oxidative-stress induced renal-failure should be considered.     

不同剂量右美托咪定对肺癌根治术后认知功能的影响

目的：探讨不同剂量右美托咪定麻醉对肺癌根治术患者术后认知功能的影响。方法：选取我院收治的肺癌根治术患者60 例,根据不同剂量的右美托咪定分为A 组（高剂量）、B组（低剂量组）及C 组（不加右美托咪定）,每组各20 例。比较三组患者治疗 前后超氧化物歧化酶（SOD）活性、丙二醛（MDA）、苏醒时间、拔管时间以及认知功能。结果：三组患者的基线资料及术中情况比较 无差异,P＞0.05;术后SOD 水平呈先降低后升高的趋势,MDA呈先升高后降低的趋势。A组在第三天时SOD值较其他两组高, MDA在第1天与第3 天时较其他两组低,P＜0.05;术后1 天认知程度比较,A 组认知功能较其他两组高,P＜0.05;三组苏醒时间 和拔管时间相比较,A 组明显优于其他两组,P＜0.05。结论：右美托咪定麻醉能够降低氧化应激损伤,影响肺癌根治术患者术后认 知功能,缩短苏醒时间、拔管时间。     

Distribution,Elimination, and Renal Effects of Single Oral Doses of Europium in Rats

Single doses of europium (III) chloride hexahydrate were orally administered to several groups of rats. Cumulative urine samples were taken at 0–24 h, and blood samples were drawn after 24-h administration. The europium concentration was determined in these samples by inductively coupled plasma atomic emission spectroscopy. The volume, creatinine, ß-2-microglobulin, and N-acetyl-ß-d-glucosaminidase were measured in the urine samples to evaluate possible europium-induced renal effects. The blood samples showed low europium distribution, with an average of 77.5 μg/L for all groups. Although the urinary concentration and excretion showed dose-dependent increases, the percentage of europium excreted showed a dose-dependent decrease, with an average of 0.31% in all groups. The administration of europium resulted in a significant decrease of creatinine and a significant increase of urinary volume, N-acetyl-ß-d-glucosaminidase, and ß-2-microglobulin. Rare earth elements, including europium, are believed to form colloidal conjugates that deposit in the reticuloendothelial system and glomeruli. This specific reaction may contribute to low europium bioavailability and renal function disturbances. Despite low bioavailability, the high performance of the analytical method for determination of europium makes the blood and urine sampling suitable tools for monitoring of exposure to this element. The results presented in this study will be of great importance in future studies on the health impacts of rare earth elements.     

Membrane Tension Modulates the Effects of Apical Cholesterol on the Renal Epithelial Sodium Channel

We used patch-clamp techniques and A6 distal nephron cells as a model to determine how cholesterol regulates the renal epithelial sodium channel (ENaC). We found that luminal methyl-β-cyclodextrin (mβCD, a cholesterol scavenger) did not acutely affect ENaC activity at a previously used concentration of 10 mm but significantly decreased ENaC activity both when the cell membrane was stretched and at a higher concentration of 50 mm. Luminal cholesterol had no effect on ENaC activity at a concentration of 50 μg/ml but significantly increased ENaC activity both when the cell membrane was stretched and at a higher concentration of 200 μg/ml. Confocal microscopy data indicate that membrane tension facilitates both mβCD extraction of cholesterol and A6 cell uptake of exogenous cholesterol. Together with previous findings that cholesterol in the apical membrane is tightly packed with sphingolipids and that stretch can affect lipid distribution, our data suggest that membrane tension modulates the effects of mβCD and cholesterol on ENaC activity, probably by facilitating both extraction and enrichment of apical cholesterol.     

甲基强的松龙对体外循环下心脏瓣膜置换患者肾功能的影响

背景与目的:有研究表明甲基强的松龙可减轻体外循环所致的肺损伤,但其对体外循环患者术后肾功能损害的作用尚不十分清楚。本文探讨甲基强的松龙是否有效抑制体外循环心内直视术中的炎症反应,并对肾脏有保护作用。方法:随机选取40例体外循环下择期行心脏瓣膜置换手术的患者,年龄30～55岁,心功能Ⅱ～Ⅲ级,随机分为甲基强的松龙组和对照组,每组20例。甲基强的松龙(MPS)组于体外循环前以甲基强的松龙10mg/kg预冲,对照组(NS)以等量的生理盐水代替。于CPB前(T1),CPB结束后2h(T2)、CPB结束后12h(T3),CPB结束后24h(T4),等时点留取中心静脉血和尿液,以酶联免疫吸附实验(ELISA)法检测炎性介质(IL-6、TNF-α、IL-10);取尿上清液检测反映肾功能的早期敏感指标:尿-N-乙酰氨基-葡萄糖苷酶(NAG)、尿α1-微球蛋白(α1-MG)、尿视黄醇结合蛋白(RBP)的水平。结果:CPB前两组炎性介质和肾功检测指标,差异均无统计学意义(P>0.05),而CPB结束后,两组炎性介质的水平和肾功各项指标均较术前增高。与NS相比,MP组T2~T4时点IL-6水平明显降低(P<0.05)。在T2~T3时点TNF-α的水平明显低于对照组(P<0.05)。两组IL-10的水平在CPB后均增加,但在T2~T3时点MP组升高幅度明显高于NS组(P<0.05)。与NS比较,MP组在CPB后各时点尿NAG、α1-MG、RBP的水平均明显降低(P<0.05)。结论:CPB可导致全身炎性反应及肾功能损伤;甲基强的松龙可减轻炎性反应,同时对肾功能有一定的保护作用。     

不同剂量百令胶囊联合非布司他对慢性肾功能不全伴高尿酸血症患者肾功能及血脂水平的影响

目的:探讨不同剂量百令胶囊联合非布司他对慢性肾功能不全(CRF)伴高尿酸血症(HU)肾功能及血脂水平的影响。方法:选取2017年7月至2018年8月三亚市人民医院收治的CRF伴HU患者167例为研究对象,按照数表法随机分为大剂量联合组(n=42)、中剂量联合组(n=42)、小剂量联合组(n=42)和非布司他单用组(n=41),所有研究对象均给予非布司他(40 mg/次,1次/日)治疗,大、中、小剂量联合组再分别给予百令胶囊3g/次、2g/次、1g/次,均3次/日。比较治疗后的临床疗效、治疗前后肾功能指标[血肌酐(Scr)、血尿素氮(BUN)、血尿酸(UA)、血β_2微球蛋白(血β_2-MG)、尿β_2-MG、24 h尿蛋白定量]、血脂指标[甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)]水平以及不良反应。结果:治疗后,大剂量联合组肾功能及高尿酸血症的临床总有效率最优(P0.05),其次为中剂量联合组,小剂量联合组和非布司他单用组比较差异无统计学意义(P0.05);各组患者治疗后BUN、Scr、UA、血β_2-MG、尿β_2-MG、24h尿蛋白定量水平均有不同程度的下降,其中大剂量联合组降低最显著(P0.05),小剂量联合组和非布司他单用组比较差异无统计学意义(P0.05);大、中、小剂量联合组患者治疗后TG、TC、LDL均有下降,HDL上升,其中大剂量联合组TG、TC、LDL降低最显著(P0.05),HDL升高最显著(P0.05);各组患者不良反应发生率比较无统计学差异(P0.05)。结论:大剂量百令胶囊联合非布司他治疗CRF伴HU能改善患者的肾功能和血脂指标,其不良反应发生率较低,但是稍高于其他剂量组,建议临床医师根据患者病情选择合适的剂量。     

丁酸钠通过调节SIRT1/AMPK信号通路对慢性肾衰竭大鼠肾功能的影响

摘要 目的：探讨丁酸钠（NaB）通过调节沉默信息调节因子1（SIRT1）/单磷酸腺苷活化蛋白激酶（AMPK）信号通路对慢性肾衰竭（CRF）大鼠肾功能的影响。方法：选用SD大鼠72只,随机分为6组（12只/组）：control组、Model组、NaB低剂量组（100 mg/kg）、NaB中剂量组（200 mg/kg）、NaB高剂量组（400 mg/kg）、抑制剂组（400 mg/kg NaB+2 mg/kg SIRT1/AMPK通路抑制剂EX527）;采用饲喂0.5%腺嘌呤饲料以建立CRF大鼠模型,建模成功后,灌胃和腹腔注射相应药物。使用试剂盒检测大鼠24 h尿蛋白（24 h U-pro）、血清肌酐（SCr）、尿素氮（BUN）水平;采用苏木精-伊红（HE）及Masson染色法观察肾脏病理改变,并计算胶原容积分数（CVF）;采用茜素红染色法与主动脉钙含量测定评估主动脉钙化情况;采用酶联免疫吸附法（ELISA）检测各组大鼠肾脏组织白细胞介素（IL）-6、IL-β、肿瘤坏死因子（TNF）-α水平;采用过氧化氢酶（CAT）、丙二醛（MDA）、活性氧（ROS）检测试剂盒检测大鼠肾脏组织中CAT、MDA、ROS水平;采用蛋白免疫印迹法（WB）检测各组大鼠SIRT1/AMPK信号通路及骨形态发生蛋白2（BMP2）、Runt相关转录因子2（Runx2）蛋白的表达。结果：与control组比较,Model组大鼠肾脏组织损伤严重、胶原纤维沉积显著、主动脉钙化严重,CAT活性、SIRT1、p-AMPK/AMPK表达水平显著降低（P<0.05）,CVF、主动脉钙含量和SCr、BUN、24 h U-pro、IL-6、IL-β、TNF-α、MDA、ROS水平及BMP2、Runx2蛋白表达水平显著升高（P<0.05）;与Model组比较,NaB低、中、高剂量组大鼠肾脏组织损伤减轻、胶原纤维沉积面积明显减少、主动脉钙化程度减轻,CVF、主动脉钙含量和SCr、BUN、24 h U-pro、IL-6、IL-β、TNF-α、MDA、ROS水平及BMP2、Runx2蛋白表达水平显著降低（P<0.05）,CAT活性、SIRT1、p-AMPK/AMPK表达水平显著升高（P<0.05）;SIRT1/AMPK通路抑制剂EX527可降低高剂量NaB对CRF大鼠主动脉钙化和肾功能的改善作用（P<0.05）。结论：NaB可能通过激活SIRT1/AMPK信号通路,减轻肾脏组织炎症、氧化应激损伤、主动脉钙化和肾纤维化,从而起到改善CRF大鼠肾功能的作用。