Corticosteroid metabolism in isolated rat kidney in vitro

Kidneys of male Sprague Dawley rats have been isolated and perfused in vitro in order to study the metabolism of corticosterone (B). B is the main endogenous corticosteroid in this species. Using³H-B and HPLC for the separation of steroid metabolites it has been possible to detect radioactive derivatives of B which have been denoted as met I, II and III. These substances were purified and compared with authentic reference hormones under different isocratic and gradient elution techniques. We observed chromatographic identity of met I with 11-dehydro-20-dihydro-B, of met II with 20-dihydro-B and of met III with 5-H-4,5-dihydro-B. From the fact that conversion of B can be observed with normal (50 g · l^–1 albumin in perfusate) and elevated (75 g · l^–1) colloid osmotic pressure of the recirculating perfusate it can be concluded that B gets access to the metabolic site in renal tissue not solely by glomerular filtration and tubular reabsorption. The metabolites identified presently are excreted in the urine. Metopirone increased the concentration of met I and decreased the concentration of met II. This is compatible with the concept of a stimulatory effect of metopirone on a C-20-hydroxysteroid oxidoreductase and a C-11-hydroxysteroid dehydrogenase.Abbreviations aldo aldosterone - B corticosterone - ³H-B (1,2,6,7-³H)-corticosterone - CS corticosteroid - HPLC high pressure liquid chromatography - met I (II, III) metabolite I (II, III) - P perfusate - U urine - KH kidney homogenate - MS mass spectrometry - ESR external standard ratio - n-hex n-hexane (spectrograde) - isoprop Isopropanol (spectrograde) This study has been supported by the Deutsche Forschungsgemeinschaft (Hi 97/16-1). Parts of this study have been presented at the 54. Meeting of the Deutsche Physiologische Gesellschaft, Innsbruck 1981 [34], at the 6. Int. Symp. on the Biochem. of Kidney Functions, Bischoffsheim 1982 [11], and the 15. Symp. of the Gesellschaft für Nephrologie, Basel 1982 [12]. Furthermore parts of the data are presented in [35]     

Aldosterone metabolism in rat renal tissue in vitro

In the present study the formation of lipid soluble metabolites from³H-aldosterone was investigated in vitro in isolated kidneys and kidney and liver slices of Sprague Dawley rats. The steroids were separated by HPLC (forward and reversed phase systems) and detected on-line as UV- or³H-chromatograms. Apart from an unenzymatically formed substance, isoaldosterone, three less polar metabolites were traced (A1, A2, A3). The structure of the quantitatively most important metabolite (A1), was identified as 5-dihydroaldosterone using a combination of techniques such as chromatographic comparison with reference steroids, antibody binding and mass spectrometry. Evidence for further conversion of DHaldo to 3,5-tetrahydroaldosterone was obtained in chromatographic and antibody binding studies. The formation of metabolites was not dependent on glomerular filtration. Furthermore it displayed regional heterogeneity with highest activity in the outer medulla. Finally it was observed that the in vitro metabolism of aldosterone was not saturable over a range of initial aldo concentration of 10^–9 to 10^–5 M.Abbreviations Aldo aldosterone - B corticosterone - CS corticosteroids - HPLC high pressure liquid chromatography - KH Krebs-Henseleit - MCS mineralocorticosteroid - MeOH methanol - met metabolite - MS mass spectrometry - TH(DH) tetrahydro-(dihydro) - t _R retention time Supported by the Deutsche Forschungsgemeinschaft, Hi97/16. Parts of this work have been presented at the 61st Meeting of the Deutsche Physiologische Gesellschaft, Berlin [1]     

Lipid and protein metabolism in asthma. Effects of diet and corticosteroid therapy

BACKGROUND: Because little is known about the effects of asthma and asthma therapy on lipid and protein metabolism, we have investigated the characteristics of diet and plasma/serum levels of fat and protein in a group of asthma patients with various degrees of severity. METHODS: A case-control study was carried out on 118 asthma patients recruited from an outpatient clinic and 121 healthy subjects. Asthma severity was characterized in four groups according to clinical symptoms, lung-function tests, and therapy. Normal dietary intake was estimated from a food frequency questionnaire. Serum protein, albumin, and fatty acids were determined by standard methods. RESULTS: The dietary energy intake of the asthmatics was significantly lower than that of the controls. However, no differences in the body mass index were found between asthma patients and healthy subjects. There were no differences in serum/plasma levels in any of the measured biochemical parameters between healthy subjects and asthmatics. Plasma levels of protein and albumin were significantly lower in severely corticosteroid-dependent patients. There was a significant negative correlation between plasma protein (r=0.36, P<0.05) and plasma albumin levels (r=0.43, P<0.01) and the daily dose of oral corticosteroids. We did not find any differences in plasma levels of cholesterol, HDL-cholesterol, LDL-cholesterol, and fatty acids between cortico-dependent patients and those not receiving this therapy. No correlation was found between any biochemical parameters and the daily dose of inhaled corticosteroids. CONCLUSIONS: Our results suggest that asthma induces a decrease in energy intake that does not result in a decreased body weight. Inhaled corticosteroids do not exert any metabolic effect, whereas severe asthma with regular oral corticosteroid therapy is associated with reduced plasma protein and albumin levels.     

Role of aldosterone in the mechanism of renal potassium adaptation

Chronic potassium loading results in an adaptive change in renal tubular epithelium which increases the capacity for potassium excretion. The present study was performed to evaluate the role of aldosterone in renal potassium adaptation, since hyperaldosteronism stimulates potassium secretion, and potassium loading increases the production of aldosterone. Experiments were performed in animals with intact adrenal glands, and in adrenalectomized animals (Adx) replaced with basal physiologic amounts of corticosterone, which 1) were not replaced with aldosterone, or 2) were chronically infused with aldosterone to achieve either basal plasma levels or elevated levels.Chronic potassium loading in adrenal intact animals was associated with a statistically significant higher rate of urinary potassium excretion (3.57±0.30 Eq/min/100 g BW) compared to the control rate (2.54±0.25 Eq/min/100 g BW, p<0.05), during acute infusion of KCl. In potassium loaded Adx animals, with selective replacement of adrenal hormones, the maximum rate of potassium excretion was blunted in the absence of aldosterone, compared to potassium loaded animals with intact adrenal glands. In contrast, when Adx animals were infused chronically with aldosterone, to achieve basal or elevated plasma levels, the maximum rate of potassium excretion was not blunted, although at basal aldosterone levels increased potassium excretion was due, at least in part, to hyperkalemia.These results indicate that the infuction of renal potassium adaptation after a week or more of chronic potassium loading is dependent on the action of hyperaldosteronism on renal tubular epithelium.     

NaDC3过表达对人肾小管细胞能量代谢和活性氧产生的影响

目的:研究三羧酸循环中间代谢产物转运蛋白-高亲和力钠依赖性二羧酸转运蛋白(NaDC3)基因过表达对人肾小管细胞能量代谢与活性氧(ROS)产生的影响。方法:用重组NaDC3逆转录病毒载体感染人肾小管上皮细胞HKC。用Western blotting检测细胞中外源性NaDC3蛋白的表达水平。通过液体闪烁法测定细胞内同位素[3H]标记琥珀酸(NaDC3的转运底物)的浓度。分别用Clark电极法和反相高压液相法测定细胞内氧耗量和ATP含量。分别用荧光探针JC-1和CM-H2DCFDA处理细胞后通过激光共聚焦显微镜检测线粒体膜电位和细胞内ROS含量。结果:Western blotting结果显示导入外源NaDC3基因后可使细胞内NaDC3蛋白的表达水平明显增加。转运实验显示NaDC3病毒感染细胞内的[3H]-琥珀酸水平明显高于未感染和对照载体感染细胞。NaDC3病毒感染细胞中的氧耗量和ATP含量明显高于未感染和对照载体感染细胞。激光共聚焦检测显示,与未感染和对照载体感染细胞相比,NaDC3感染细胞的线粒体膜电位和ROS水平明显增加。结论:NaDC3过表达可通过转运过多的三羧酸循环中间代谢产物进入细胞内而加快肾小管上皮细胞能量代谢的速率、增加细胞内ROS的产生水平。     

Steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy

AIM: We investigated the effect of massive doses of corticosteroid therapy on bone metabolism using specific biochemical markers of bone metabolism, and the prevalence of osteonecrosis in severe acute respiratory syndrome (SARS) patients at a university teaching hospital in Hong Kong. METHODS: Seventy-one patients with a clinical diagnosis of SARS were studied according to the modified World Health Organization case definition of SARS who were involved in the SARS epidemic between 10 March and 20 June 2003. The clinical diagnosis was confirmed by serological test and/or molecular analysis. Biochemical markers of bone metabolism were analysed retrospectively using serial clotted blood samples collected from each patient during the course of hospital admission to discharge and subsequent follow-up at out-patient clinic using the arbitrary time periods: (i) Day <10; (ii) Day 28-44; (iii) Day 51-84; and (iv) Day >90 after the onset of fever. Magnetic resonance imaging of the knee and hip joints were performed post-admission to evaluate the prevalence of osteonecrosis amongst these SARS patients. Various risk factors for the development of osteonecrosis were assessed using receiver operating characteristics curve comparison with appropriate test statistics and Spearman's coefficients of rank correlation with biochemical bone markers. RESULTS: Biochemical markers of bone metabolism showed significant bone resorption as evidenced by a marked increase in serum C-terminal telopeptide concentration (CTx) from Day 28-44 after the onset of fever. With tapering down of corticosteroid dosage, CTx started to return to previous baseline level from Day 51 onwards, while other bone formation markers, serum osteocalcin and bone-specific alkaline phosphatase concentrations (OC and BALP, respectively), started to increase. The latter effect was even more marked after Day >90. Seven patients developed radiological evidence of osteonecrosis. The prevalence of osteonecrosis in this cohort was 9.9%. A total corticosteroid dosage of >1900 mg hydrocortisone, >2000 mg methylprednisolone, >13 340 mg hydrocortisone-equivalent corticosteroid therapy, and >18 days on corticosteroid therapy were found to be significant risk factors for the subsequent development of osteonecrosis. There were also significant positive correlations amongst various biochemical bone markers in this patient cohort. CONCLUSIONS: Both bone resorption and formation markers were unable to predict the subsequent development of osteonecrosis. The use of high dose of hydrocortisone or methylprednisolone for an extended duration was shown to be a significant risk factor for osteonecrosis. Its prevalence in this cohort is comparable to those reported in the literature for SARS patients with high-dose corticosteroid therapy. The Day 28-44 increase in the serum CTx coincided with the timing of corticosteroid use. The Day >51 increase in serum OC and BALP coincided with the timing of corticosteroid withdrawal.     

肾活检组织中NEP的表达及其与尿NEP含量之间的相关性研究

目的 观察肾活检组织中NEP的表达,研究它与尿NEP含量之间的关系,以期探讨检测尿NEP的临床意义。方法 将研究组分为对照组(n=100),肾小球疾病组(n=31)、急性肾小管损伤组(n=44)、慢性肾小管损伤组(n=61)、慢性肾功能衰竭组(n=13)。收集各组病人晨尿,然后通过荧光光谱分析,得到尿中NEP的量,并用相应尿肌酐值予以标化。同时对病人组中的68例患者的肾组织切片用免疫组化的方法进行染色,直接观察NEP的在肾组织中的表达情况,且进行其表达量与尿NEP的相关性研究。结果 正常对照组尿NEP为68.41ug/mmol Cr,急性肾小管损伤组尿NEP196.36ug/mmol Cr,明显高于正常对照组(P=0.0001),慢性肾小管损伤组、肾小球疾病所致的CRF组尿NEP分别为31.98、19.40ug/mmol Cr,均明显低于正常对照组(P均<0.01),而单纯肾小球疾病组尿NEP为75.49ug/mmol Cr,与正常对照组无差异(P=0.1425)。在急性肾小管损伤组和慢性肾小管损伤组,尿NEP与肾组织中NEP的表达均呈正相关,而肾小球疾病组内尿NEP与肾组织中NEP的表达无明显相关性。结论 肾小管刷状缘上NEP的表达量与近端小管损伤有良好相关性,尿NEP量实际反映近端小管刷状缘损伤情况。本研究在国内率先建立了尿NEP的检测方法,并用于临床研究。对尿中NEP的检测,提供了一种快速、非损伤性测量手     

Corticosteroid metabolism in rat kidney in vitro

An attempt has been made to identify the subcellular localization of renal corticosteroid metabolism. Subcellular fractions were prepared by differential centrifugation, identified by marker enzymes and incubated under different conditions with corticosterone (B). The NADP⁺/NADPH dependent metabolism of B could be localized in the nuclear and microsomal fraction. The most prominent metabolite was 11-dehydro-B, which is formed by 11-hydroxysteroid dehydrogenase (EC 1.1.1.146). Enzyme kinetic studies of this enzyme with B as substrate revealed apparentK _m-values in the range of 10^–7 M for both the nuclear and microsomal fraction.Abbreviations B corticosterone - G-6-P glucose-6-phosphatase - SDH succinic dehydrogenase - 11-HSD 11-hydroxysteroid dehydrogenase - HPLC high pressure liquid chromatography - met metabolite - STM (STE and DTE) as explained in legend to Fig. 1 Dedicated to Prof. K. J. Ullrich on the occasion of his 60th birthday     

A modified Sperber technique for direct estimation of true renal tubular excretion fraction

The Sperber technique in the hen is particularly suitable for the study of renal tubular secretion. However, results obtained with this technique vary considerably, due to an unpredictable and highly variable shunting of renal portal blood. In an attempt to get a total and stable renal perfusion by portal blood from the leg, appropriate shunt vessels were ligated. This procedure was found to force all portal blood from the leg to perfuse the ligated kidney, without affecting the symmetry of glomerular filtration or renal clearance of 125-I-Na-o-iodohippurate between the kidneys. In conclusion, the abolition of renal portal shunt flow allows use of the Sperber technique for a direct estimation of the true tubular excretion fraction (TTEF) of a substance. Thus, TTEF_PAH, a measure of the tubular excretion efficiency of para-amino-hippuric acid, was found to be about 70%. The stable renal perfusion in ligated animals will also facilitate comparative studies of renal tubular excretion in the hen. Moreover, no animal has to be rejected due to a low renal perfusion of portal blood. Furthermore, the use of ligated hens makes it unnecessary to use markers for the renal perfusion of portal blood when steady-state experiments are performed. Finally, the total renal perfusion of portal blood in ligated animals will facilitate the demonstration of a secretory component in the renal handling of substances with a low affinity for the renal transport system.     

Over-expression of glucose transporter isoform GLUT1 and hexokinase I in rat renal oncocytic tubules and oncocytomas

Renal oncocytomas, which have previously been shown to originate from the collecting duct system, were induced in male Sprague-Dawley rats by oral administration of N-nitrosomorpholine (NNM) for 7 weeks. The expression of glucose transporter isoforms GLUT1 and GLUT2, and of several enzymes involved in glucose metabolism [hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH)] were studied by cytochemical approaches in serial cryostat sections of the kidney 12, 23 and 34 weeks after withdrawal of NNM. Oncocytic tubules connected with collecting ducts were first observed 23 weeks, and oncocytomas 34 weeks after withdrawal. The cytochemical pattern of oncocytic tubules and oncocytomas was similar, but differed markedly from that of normal collecting ducts in nearly all variables studied; expression of GLUT1 and hexokinase I proteins were strongly increased; activities of HK, PK and MDH were elevated, while LDH activity was reduced. These results suggest that oncocytic transformation is associated with fundamental changes in energy metabolism which differ from those in cell lineages leading to other types of renal cell tumours, such as clear/acidophilic and basophilic cell tumours. The characteristic over-expression of GLUT1 may be used as a diagnostic criterion for the discrimination between oncocytes and acidophilic (granular) cells in clear/acidophilic renal cell tumours which show a reduced expression of this glucose transporter protein.     

Effects of hypercalcemia on water and sodium excretion by the isolated dog kidney

Summary The effects of acute hypercalcemia on hemodynamics and on water and sodium excretion were studied on the blood-perfused isolated dog kidney. This model advantageously eliminates various factors which modify medullary osmolality and intrarenal hemodynamics, as well as collecting duct permeability. Calcium ion directly inhibits sodium reabsorption in the proximal tubule and in the ascending limb of Henle's loop, leading to increased sodium excretion rate and to decreased free water generation. The vasoconstrictive action of calcium, leading to decreased glomerular filtration rate, may mitigate the strong natriuretic effect of this ion.     

Renal handling of calcium and phosphate

Summary In glomerular filtrate, calcium concentration (UF) is some 50–70% of total plasma calcium concentration. About 60% of filtered calcium is reabsorbed in the proximal convoluted tubule, some 15% in pars recta, 15% in the thick ascending limb, and 9% in the distal convoluted tubule including the granular portion of the cortical collecting duct. About 1% is excreted. Approximately 2/3 of proximal tubular calcium transport is passive, driven by a chemical (TF/UF=1.1) and electrical (2 mV, lumen positive) gradient; 1/3 is active, whereby calcium enters the cell at the brush border membrane by passive diffusion and is pumped out at the basolateral membrane in exchange for sodium. Transport in distal convoluted tubules is entirely active and operates both against a chemical (TF/UF 0.3–0.7) and electrical (10–70 mV, lumen negative) gradient. Although saturability of transport is not detectable in microperfusion studies, enhancement of plasma calcium leads to calciuria. Factors stimulating calcium reabsorption are parathyrin, 1.25(OH)₂D₃, thiazides, and alkalosis. Factors inhibiting calcium reabsorption are calcitonin, growth hormone, thyroid hormone, chronic application of mineralo- and glucocorticoids, insulin, glucose, acidosis, sodium infusion, acetazolamide, furosemide, and mannitol.Phosphate concentration in ultrafiltrate is some 90% of total plasma concentration. In intact animals about 2/3 of filtered phosphate is reabsorbed in proximal convoluted tubules, and some 20% is excreted in urine. Shortly after thyroparathreoidectomy (TPTX), 80% of filtered phosphate is reabsorbed in the proximal convoluted tubule, 15% in the pars recta, and 2% is excreted in the urine. Thus, less phosphate is excreted in urine (20% in intact, 2% in TPTX animals) as is recovered in late distal convoluted tubules of superficial nephrons (35% and 5%, respectively). The discrepancy is at least partially due to more avid reabsorption in deep nephrons. Furthermore, evidence exists in favor of phosphate reabsorption in the arcades or collecting duct. Phosphate reabsorption in proximal convoluted tubule and pars recta is active. Uptake of phosphate at the brush border membrane is uphill and is driven by coupling with two sodium ions, whereas exit at the basolateral membrane may be entirely passive. At increasing plasma phosphate concentrations, reabsorption is saturated and excess filtered phosphate excreted. Factors stimulating phosphate transport are phosphate depletion, acute 1,25(OH)₂D₃, thyroxin, growth hormone, magnesium, lithium, and metabolic acidosis. Factors inhibiting phosphate transport are high phosphate or high calcium diets, parathyrin, calcitonin, chronic 1,25(OH)₂D₃, hypocalcemia, magnesium deficiency, respiratory acidosis, metabolic alkalosis, glucose, colchicine, NaCl-infusions, thiazides, furosemide, ethacrynic acid, mannitol, and acetazolamide.     

甲状腺激素导致糖代谢异常机制的研究进展

甲状腺激素在体内糖代谢平衡中发挥重要作用,可以通过直接或间接作用于肝脏、骨骼肌、脂肪组织等重要的脏器调节葡萄糖的代谢。本文就甲状腺激素对糖代谢调节及其机制的研究进展及甲状腺疾病与胰岛素抵抗之间的关系进行综述。     

老年肾脏病患者血清Klotho水平与肾功能不全关系的研究

目的 探讨老年慢性肾脏病(chronic kidney disease,CKD)患者血清Klotho水平变化与肾功能不全的关系及影响因素.方法 收集我院CKD患者100例,根据年龄分为老年组41例(年龄65≥岁)及非老年组59例(年龄＜65岁)、匹配健康对照组30例,采用ELISA法分别检测三组受试者血清Klotho水平,并进一步分析其与肾功能不全的关系及影响因素.结果 CKD组血清Klotho水平明显低于对照组;其中,老年CKD组血清Klotho水平又明显低于非老年组(P＜0.05);在排除肾功能的影响后,老年组血清Klotho水平仍然低于非老年组,差异有统计学意义;Pearson相关分析显示,老年患者血清log Klotho水平与血钙、体重、血色素、GFR呈正相关,与年龄、log FGF-23、log Scr、血磷呈负相关;多元逐步回归分析显示,年龄、log FGF-23、log Scr是影响老年组患者血清log Klotho水平的独立危险因素.结论 CKD患者血清Klotho水平下降,其中老年组患者Klotho水平的较非老年组减少更明显,Klotho的减少可能参与了老年CKD的发生发展.     

Administration of dehydroepiandrosterone enanthate to oophorectomized women - effects on sex hormones and lipid metabolism

Eight bilaterally oophorectomized women were given a depot injection of 200 mg DHEA-enanthate to study the effect on endocrine and lipid metabolism.

A decrease in sex-hormone binding globulin (SHBG) and an increase in androstenedione was found 14 and 30 days after the injection. No changes could be detected in LH, FSH, oestrone, oestradiol or oestriol. Testosterone showed a tendency towards an increase. As compared to pre-treatment values, plasma lipids were unaltered after 30 days. A decrease in high density lipoproteins (HDL), cholesterol and in very low density lipoproteins (VLDL), free cholesterol, total cholesterol and phospholipids were seen in the lipid composition of the lipoproteins on day 30. These findings are in agreement with previous data reported after the administration of drugs with androgen-like effects. The relative fatty acid composition of plasma lecithin revealed only minor changes while the fatty acid composition of cholesterol esters indicated a decreased portion of essential fatty acids. These results suggest, in agreement with previous studies, an impaired endogenous cholesterol formation in the liver. The results from the analysis of the fatty acid composition of lecithin and cholesterol esters might indicate a decreased percentage of exogenous (dietary) cholesterol ester in plasma.     

Renal tubular transport and metabolism of carboxyamidated and glycine-extended gastrins in pigs

Renal handling of postprandial and intravenously administered gastrin was investigated in anaesthetised pigs. The fractional extraction of postprandial carboxyamidated and glycine-extended gastrin in the kidneys was 0.21 ± 0.01 and 0.16 ± 0.02, but the respective urinary clearance comprised only 0.57 ± 0.03 and 0.44 ± 0.05% of the GFR (P < 0.02). The respective total body clearance of carboxyamidated and glycine-extended gastrin-17 (gastrin-17 and gastrin-17Gly) during continuous infusion was 22.9 ± 1.5 and 19.6 ± 1.4 mL kg^?1 min^?1 (NS), and the renal fractional extraction of the peptides was 0.31 ± 0.03 and 0.29 ± 0.05, respectively. The kidneys accounted for 8% of total body clearance of gastrin-17. Renal filtration rate of gastrin-17 exceeded renal extraction rate (9.739 ± 0.487 vs. 6.407 ± 0.321 pmol min^?1). Urinary clearance of gastrin-17 and gastrin-17Gly amounted only 0.91 ± 0.16 and 0.13 ± 0.03%, respectively, of the GFR (P < 0.01), but urinary excretion rate correlated with the filtered amount of the peptides (r = 0.93, P < 0.01). Neither was a renal plasma threshold recorded nor was a T_m value for tubular uptake or degradation of gastrin achieved in spite of supraphysiological plasma levels of the peptides. The results indicate that filtered gastrin is almost completely removed in the renal tubules, primary by metabolism although part of the absorbed peptides may be returned to the circulation in intact form. The process for uptake or metabolism has a high capacity but varies with the molecular form of gastrin.     

CRRT治疗应用于危重急性肾损伤对患者 肾功能及病死率的影响

目的 探讨连续性肾脏替代治疗（CRRT）应用于危重急性肾损伤对患者肾功能及病死率的影响。方法 回顾性分析2016年1月~2018年12月我院102例危重急性肾损伤患者的临床资料,根据患者所采取的治疗方式分成观察组60例和对照组42例。观察组采取原发病对症治疗及CRRT治疗,对照组接受原发病对症治疗。比较两组患者治疗1周后肾功能指标[血肌酐（Scr）、尿素氮（BUN）]变化及住院病死率。结果 治疗1周后,两组Scr、BUN水平均较治疗前降低,观察组Scr和BUN分别为（173.35±43.18）μmol/L和（13.12±4.06）mmol/L,低于对照组的（221.73±60.56）μmol/L和（16.71±4.17）mmol/L,差异具有统计学意义（P＜0.05）;观察组患者28 d住院病死率低于对照组（31.67% vs 57.14%）,差异具有统计学意义（P＜0.05）。结论 CRRT治疗可以更有效地改善急性肾损伤患者的肾功能,并显著降低患者住院病死率。     

Effects of high oxygen tension on the metabolism of vasoactive hormones in isolated perfused rat lungs

The effect of exposure of rats to high concentrations of oxygen (90–95%, normobaric) on the activation of angiotensin I to angiotensin II and on the inactivation of bradykinin, prostaglandin E₂ (PGE₂) and 5-hydroxytryptamine (serotonin) in the pulmonary circulation of isolated perfused rat lungs was investigated. After 36 h exposure, PGE₂ survival in the pulmonary circulation increased and reached 3 times the control value after 48 h exposure. A decrease in the conversion of angiotensin I to angiotensin II was seen after 48 h exposure. No decrease in the inactivation of 5-hydroxytryptamine was seen until after 60 h exposure. At this time bradykinin inactivation was also decreased. The decrease in metabolism of angiotensin I and PGE₂ following 48 h exposure to oxygen was reversed by a subsequent exposure to room air for 12 h. In these experiments, therefore, the earliest sign of oxygen toxicity was a decrease in PGE₂ metabolism, a reaction associated with cells other than endothelial cells.     

叉头框蛋白O1在内毒素血症急性肾损伤中的作用

目的:探讨叉头框蛋白O1(forkhead box protein O1,FOXO1)在内毒素血症急性肾损伤(acute kidney injury,AKI)中的作用及相关机制。方法:6～8周龄雄性C57BL/6小鼠腹腔内注射脂多糖(lipopolysaccharide,LPS; 10 mg/kg)诱导内毒素血症AKI模型,检测血清肌酐和血尿素氮。利用Western blot、RT-qPCR和免疫荧光等方法检测小鼠肾组织内FOXO1的表达变化。体外培养人近端肾小管上皮细胞HK-2,LPS诱导内毒素血症AKI肾小管上皮细胞模型,利用FOXO1过表达腺病毒感染HK-2细胞,MTT法检测细胞活力;MitoTracker标记线粒体形态学变化;Mito-SOX检测线粒体超氧化物含量改变;检测FOXO1、促凋亡因子Bax及线粒体氧化磷酸化相关分子mRNA变化,以观察线粒体氧化损伤变化情况。结果:内毒素血症AKI小鼠肾组织FOXO1 mRNA及蛋白表达下调。体外LPS刺激可引起HK-2细胞活力下降,线粒体片段化改变,线粒体超氧化物含量升高,FOXO1 mRNA及蛋白表达下调,Bax表达上调,线粒体氧...