浅低温对犬全脑缺血再灌注后脑组织形态及脑功能的影响

研究浅低温对犬心脏停跳复苏后脑组织形态学及脑功能的影响。缺血时间１８ｍｉｎ，再灌注８ｈ，观察神经机能及脑顶叶皮质形态学改变，并对顶叶皮层神经细胞及毛细血管进行体视学分析。结果表明，浅低温综合治疗可明显减轻神经细胞及毛细血管的损害，促进脑功能的恢复。     

Protection of the ischemic myocardium from reperfusion injury by prostaglandin E1 inhibition of ischemia-induced neutrophil activation

Summary This study investigates the action of intravenous PGE₁ on myocardial reperfusion injury and the possible involvement of antineutrophil activities. Cats were subjected to 3 h of temporary ligation of the left anterior descending coronary artery, followed by 2 h of reperfusion. Animals were treated with PGE₁ (5 g/kg x min) or vehicle (saline solution), starting 0.5 h after coronary artery occlusion. Vehicle-treated cats exhibited a significant loss of cardiac creatine phosphokinase specific activity at 5 h, accompanied by a significant ischemia-induced rise in the ST segment of the ECG and development of a Q wave after starting reperfusion. All of these alterations were largely prevented by PGE₁ treatment. PGE₁ exerted some blood-pressurelowering activity at 5 h (P > 0.05) but did not reduce myocardial contractile force and oxygen consumption. PGE₁ modestly antagonized ischemia-induced formation of platelet aggregates. However, PGE₁ prevented the rise in peripheral white blood cell count during ischemia and reperfusion and inhibited the generation of reactive oxygen species (myeloperoxidase assay) from zymosan-stimulated whole blood ex vivo. The ratio of generation of reactive oxygen species/white blood count remained unchanged. It is concluded that PGE₁ protects the ischemic myocardium from acute reperfusion injury and that this effect involves an action of the compound on neutrophils, probably by improved myocardial tissue preservation, resulting in reduced formation of chemotactic products and, consequently, less local neutrophil accumulation and release of noxious metabolites.Parts of these results have been presented to the 29th Spring meeting of the Deutsche Gesellschaft für Pharmakologie und Toxikologie, Mainz, 1988 Send offprint requests to K. Schrör at the above address     

Effect of a protein binding change on unbound and total plasma concentrations for drugs of intermediate hepatic extraction

For substances eliminated from blood by the liver, the effect of a change in unbound fraction of drug (fu _b )on steady state total (C _b )and unbound (Cu _b )blood concentrations has hitherto only been considered for the two limiting cases, i.e., at the upper and lower extremes of hepatic intrinsic clearance (CL _int ).For a substance of very low CL _int ,if fu _b changes, C _t will change and Cu _b will remain constant, whereas if CL _int isvery high, Cu _b will change and C _b will remain constant.The present study defines the effects of a change in fu _b on C _b and Cu _b over the whole CL _int range. Computer simulations were undertaken which predicted that, for a given change in fu _b ,absolute and relative changes in C _b would decreasenonlinearly with increasing CL _{int, twhile the relative change in} Cu _{b would} increasewith CL _int .The absolute change in Cu_b would be independent of CL _int .Significant changes in C_b and Cu _{b would be observed at intermediate values of} CL _{int not just at the high and low extremes. These theoretical predictions were investigated experimentally in the isolated perfused rat liver by examining the effects of a change in} fu _{b of sodium taurocholate a substance with intermediate} CL _int (such that at fu _b =0.27,hepatic extraction ratio=0.71) induced by concurrent administration of sodium oleate. Sodium 24- ¹⁴ C-taurocholate (specific activity 52 Ci/mmol) was infused into the reservoir in a recycling system at 30 mol/hr for 105 min (n=6). At 45 min a bolus dose of sodium oleate (50 mmol) was administered to the reservoir, followed by a constant infusion of 143 mmol/hr for 1 hr. Following the administration of oleate, taurocholate fu _{b fell promptly by 55% (0.27–0.12). There was a relative increase of taurocholate} C _{b of 22.7% and a relative decrease in} Cu _{b of 45.4%, in accordance with the simulations (p<0.05). We conclude that important changes in unbound steady-state concentration, the pharmacologically active moiety, can occur upon changes in unbound fraction with compounds of intermediate hepatic intrinsic clearance}.This study was supported by the National Health and Medical Research Council of Australia.     

Protection of chlordecone-potentiated carbon tetrachloride hepatotoxicity and lethality by partial hepatectomy

Chlordecone (CD) pretreatment is known to markedly potentiate CCl₄ hepatotoxicity. Previous studies have shown that prior exposure to CD obtunds the increased hepatocellular regeneration and repair observed in non-treated rats challenged with a single, low dose of CCl₄. These observations allowed us to hypothesize that suppression of hepatic regeneration and tissue repair by CD + CCl₄ combination treatment might be involved in this interaction. To test this hypothesis, CCl₄ hepatotoxicity was evaluated in actively regenerating livers using CD-treated (10 ppm in the diet for 15 days), surgically partially hepatectomized (PH) male Sprague-Dawley rats. Rats undergoing no surgical manipulation (CTRL) and sham operation (SH) were included as appropriate controls. Surgical manipulations were conducted on day 15 of the dietary protocol. Based on liver-to-body weight ratios (LW/BW), mitotic indices, hepatic cytochrome P-450 content, and hepatic glutathione (GSH and GSSG) levels, PH-induced hepatocellular regeneration was not affected by pretreatment with CD. Thus, the PH model was considered valid for assessing the effects of CD + CCl₄ combination treatment. CCl₄ (100 l/kg; i.p.) was administered 1, 2, 4 or 7 days after the surgical manipulations. Hepatotoxicity was assessed 24 h later by measuring LW/BW and serum enzymes (SGPT, SGOT and ICD) in all four groups. Hepatic histopathological, histomorphometric and lethal effects were assessed in animals receiving CCl₄ 1 or 7 days after the surgical manipulations. CCl₄-induced increases in LW/BW were observed in CD + PH rats receiving CCl₄ 4 or 7 days post-PH, but not in the 1 or 2 day post-PH groups in which the hepatocellular regeneration was maximal. CCl₄-induced serum enzyme elevations were significantly less in the CD + PH rats as compared to CD + SH. This decrease in the serum enzyme elevations was most prominent in the 1 day post-PH group, where the hepatocellular mitotic activity was most pronounced. CCl₄ lethality, assessed in the 1 day post-surgical manipulation group, was also decreased in the CD + PH rats in comparison to CD + SH rats. Such a protection was not observed in rats receiving CCl₄ 7 days post-PH. These data are consistent with and are supportive of the hypothesis that a suppression of otherwise normally stimulated hepatocellular regeneration following low-dose CCl₄ administration is involved in the marked amplification of CCl₄ toxicity by CD.Abbreviations CD chlordecone - GSH reduced glutathione - GSSG oxidized glutathione - PH partial hepatectomy - SH shamhepatectomy - CTRL control, not surgically manipulated - N normal diet - LW/BW liver weight-to-body weight ratio - SGPT serum glutamic; pyruvic transaminase - SGOT serum glutamic oxaloacetic transaminase - ICD isocitrate dehydrogenase These studies were made possible by a grant from the US Environmental Protection Agency R-811072A preliminary report of these findings was presented at the 70th Annual Meetings of the Federation of American Societies for Experimental Biology at St. Louis, MO (Fed Proc 45: 1051, 1986)A. N. Bell is a Predoctoral Toxicology Trainee and Robert A. Young is a Postdoctoral Trainee supported by Toxicology Training grant from National Institute of Environmental Health Science ES-07045     

过量运动对健康大鼠肾脏结构与功能的影响

目的：观察过量运动对健康大鼠肾脏结构与功能的影响并探讨其可能机制。方法：将30只健康Sprauge-Dawley(SD)大鼠按照随机数字表随机分为安静对照组和过量运动组,每组15只。安静对照组在鼠笼内安静饲养,过量运动组进行16周高强度跑台力竭运动。实验后,测定24 h尿蛋白（UP）、血尿素氮（BUN）和血清肌酐（SCr）含量评价肾功能;分别行HE、Masson染色观察肾脏组织病理学改变,同时获取肾小球和肾小管损伤评分以及纤维化指数（FI）;免疫印迹测定转化生长因子-β1(TGF-β1)、基质金属蛋白酶-9(MMP-9)、α-平滑肌肌动蛋白（α-SMA）和E-钙黏蛋白（E-CA）蛋白表达量。结果：与安静对照组比较,过量运动组肾脏结构异常,肾小球损伤评分、肾小管损伤评分、FI、UP、BUN和SCr增加（t分别为-6.895、-7.365、-9.234、-4.964、-7.753、-16.444,均P<0.05）,MMP-9蛋白表达下调（t=5.077,P<0.05）,而TGF-β1、α-SMA和E-CA蛋白表达差异无统计学意义（t分别为-1.801、-1.129、1.585,...     

生物标志物联合检测在脓毒症相关急性肝损伤患者中的应用价值

目的:探讨生物标志物联合检测对脓毒症相关急性肝损伤患者的早期诊断和预后评估的价值。方法:收集内蒙古科技大学包头医学院第一附属医院重症医学科(ICU)2019年11月-2022年1月收治的104例脓毒症患者临床资料,按照入ICU时是否发生急性肝损伤分为脓毒症相关急性肝损伤组(n=42)和非肝损伤组(n=62),将脓毒症相关急性肝损伤患者按28 d是否存活分为存活组(n=16)和死亡组(n=26),记录104例患者入ICU 6 h内血清正五聚蛋白3(PTX-3)、C-反应蛋白(CRP)、降钙素原(PCT)、总胆红素(TBIL)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、凝血酶原时间国际标准化比值(INR值)、凝血酶原时间(PT)、凝血酶原活动度(PTA)、血小板(PLT)、入ICU 24 h内急性生理与慢性健康状况评估量表II(APACHEII)评分最差值及序贯器官衰竭评估(SOFA)评分;同时记录脓毒症相关急性肝损伤患者28 d预后。PTX-3的相关性采用Spearman相关分析;绘制受试者工作特征曲线(ROC曲线),计算ROC曲线下面积(AUC),分析各指标单独检测以及联合检测对脓毒...     

彩色多普勒超声对感染性休克患者急性肾损伤的预测价值

背景 感染性休克患者存在肾脏血液灌注异常,严重时可诱发急性肾损伤(AKI),严重威胁患者生命安全;彩色多普勒超声(CDU)可用于评估肾脏血流变化,但有关其在感染性休克患者AKI评估中价值的研究较少。目的 通过CDU评价感染性休克患者AKI的发生情况及其血流动力学改变。方法 选取2019年6月至2021年7月徐州市中心医院收治的105例确诊为感染性休克的患者并纳入感染组,选取同期健康体检者58例并纳入对照组,收集受试者一般资料。采用CDU检查受试者肾脏血流动力学指标[肾动脉管腔内径(D)、收缩期血流峰值速度(Vs)、舒张末期血流速度(Vd)、阻力指数(RI)、搏动指数(PI)],比较感染组与对照组的一般资料及肾脏血流动力学指标。根据感染组患者入院72 h内发生AKI与否将其分为AKI组及非AKI组,比较AKI组与非AKI组肾脏血流动力学指标。应用受试者工作特征(ROC)曲线分析肾脏血流动力学指标对感染性休克患者发生AKI的预测价值。应用单因素分析及多因素Logistic回归分析探讨感染性休克患者发生AKI的影响因素。以AKI由轻到重的程度将患者分为AKIⅠ组、AKIⅡ组、AKIⅢ组,比较...     

慢加急性肝衰竭诊断标准的研究进展

慢加急性肝衰竭(ACLF)是指在慢性肝病基础上遭受急性打击后,出现严重的急性肝功能失代偿,其因病情进展迅速、短期死亡率极高,引起了全球肝病学家的关注。但由于不同国家(地区)ACLF的病因及临床特征等存在明显的差异,目前国内外ACLF的诊断标准多达十余种。本文通过回顾几种较为常用的ACLF定义,以及ACLF诊断标准相关研究,比较各ACLF诊断标准之间的差异,以期帮助临床医生更好地识别ACLF、优化临床决策。目前全球尚无公认的ACLF诊断标准,国内外ACLF的诊断标准存在着较大差异,临床医生在实际工作中选用何种ACLF诊断标准应根据患者慢性肝病的病因、临床特征等因素综合考虑。     

ACE2基因通过调控Nrf2/HO-1通路改善肾缺血再灌注损伤

目的 探讨血管紧张素转化酶2(ACE2)对缺氧复氧诱导的肾小管上皮细胞HK-2氧化应激、炎症、凋亡及核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路的影响。 方法 将ACE2慢病毒转染HK-2细胞,按照实验需要分为常氧组(Control组)、缺氧复氧模型组(H/R组)、缺氧复氧转染阴性对照慢病毒组(H/R-NC组)和缺氧复氧转染ACE2慢病毒组(H/R-ACE2组)。细胞经H/R处理后,通过CCK-8法检测细胞活力;RT-PCR及ELISA法检测炎症因子白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)水平;比色法检测超氧化物歧化酶(SOD)、丙二醛(MDA)表达水平;Western blotting法检测胱天蛋白酶3(Caspase-3)、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2关联X蛋白(Bax)、Nrf2、HO-1的蛋白水平。采用Nrf2抑制剂ML385以及HO-1抑制剂SnPPIX抑制Nrf2/HO-1通路,Western blotting法检测Caspase-3、Bcl-2、Bax、Nrf2、HO-1的蛋白表达水平变化,比色法检测SOD和MDA表达变化。 结果 与Control组相比,H/R组细胞活力降低(t=7.58,P<0.001),MDA含量和炎症因子IL-6、TNF-α和IL-1β表达水平以及细胞凋亡相关蛋白Caspase-3、Bax蛋白水平均增加(t_MDA=11.08,P_MDA<0.001;t_PCR-IL-6=5.82,P_PCR-IL6<0.001;t_PCR-TNF-α=7.69,P_PCR-TNF-α<0.001;t_PCR-IL-1β=4.80,P_PCR-IL-1β=0.001;t_ELISA-IL-6=34.11,P_ELISA-IL-6<0.001;t_ELISA-TNF-α=14.12,P_ELISA-TNF-α<0.001;t_ELISA-IL-1β=9.63,P_ELISA-IL-1β<0.001;t_Caspase-3=2.73,P_Caspase-3=0.026;t_Bax=27.75,P_Bax<0.001),SOD活性、Bcl-2和ACE2蛋白水平下降(t_SOD=7.74,P_SOD<0.001;t_Bcl-2=75.49,P_Bcl-2<0.001;t_ACE2=11.41,P_ACE2<0.001)。与H/R组相比,H/R-ACE2组细胞活力增加(t=3.61,P=0.002),MDA含量和炎症因子IL-6、TNF-α和IL-1β表达水平以及细胞凋亡相关蛋白Caspase-3、Bax蛋白水平均下降(t_MDA=6.15,P_MDA<0.001;t_PCR-IL-6=3.34,P_PCR-IL-6=0.006;t_PCR-TNF-α=3.65,P_PCR-TNF-α=0.007;t_PCR-IL-1β=4.06,P_PCR-IL-1β=0.004;t_ELISA-IL-6=14.62,P_ELISA-IL-6<0.001;t_ELISA-TNF-α=10.42,P_ELISA-TNF-α<0.001;t_ELISA-IL-1β=8.65,P_ELISA-IL-1β<0.001;t_Caspase-3=3.74,P_Caspase-3=0.006;t_Bax=30.52,P_Bax<0.001),SOD活性、Bcl-2和ACE2蛋白水平增加(t_SOD=3.58,P_SOD=0.007;t_Bcl-2=63.86,P_Bcl-2<0.001;t_ACE2=58.72,P_ACE2<0.001),Nrf2/HO-1信号通路被激活蛋白水平增加(t_Nrf2=44.55,P_Nrf2<0.001;t_HO-1=14.19,P_HO-1<0.001)。然而ML385和SnPPIX处理会抑制ACE2基因过表达在H/R中HK-2细胞的保护作用(F_Bax=11.02,P_Bax=0.003;F_Bcl-2=21.48,P_Bcl-2<0.001;F_Caspase-3=20.80,P_Caspase-3<0.001;F_SOD=133.49,P_SOD<0.001;F_MDA=14.06,P_MDA=0.001)。 结论 ACE2在HK-2细胞缺氧复氧损伤中具有抑制氧化应激、调节炎症、改善凋亡的作用,Nrf2/HO-1信号通路发挥重要作用。     

中性粒细胞/淋巴细胞比值对冠状动脉旁路移植术后心肌损伤的影响

探讨患者术前中性粒细胞/淋巴细胞比值（NLR）对非体外循环下冠状动脉旁路移植术（OPCABG）后心肌损伤以及临床预后的影响。方法 选取2014年1月—2019年12月我院收治的314名行OPCABG的患者,依据患者术前NLR的三分位数分为高比值组（NLR＞2.8,n=102）、中比值组（2.8≥NLR≥1.6,n=106）以及低比值组（NLR＜1.6,n=106）。分别检测患者术前基线、术后8 h及术后24 h肌酸激酶同工酶（CKMB）及肌钙蛋白（CTnI）水平。结果 高比值组患者术后心肌损伤发生率显著高于中比值组及低比值组（P＜0.05）。高比值组术后CKMB峰值显著高于中比值组［2.1(1.2～13.0) ng/mL vs2.0(1.0～7.3) ng/mL, P=0.047］及低比值组［2.1(1.2～13.0) ng/mL vs1.1(0.9～1.6) ng/mL, P＜0.001］。且高比值组患者术后CTnI峰值同样显著高于中比值组［0.075(0.010～0.185) ng/mL vs 0.020(0.000～0.103) ng/mL, P=0.011］,以及低比值组［0.075(0.010～0.185) ng/mL vs0.010(0.000～0.030) ng/mL, P＜0.001］。术前NLR较高是术后患者CTnI升高的独立危险因素（OR：2.809; 95%CI:1.326～5.954; P=0.007）。高比值组患者1年不良心血管事件发生率显著高于中比值组及低比值组（HR：1.80; 95%CI:1.16～2.79; Log Rank P=0.021）。结论 患者术前中性粒细胞/淋巴细胞比值升高是非体外循环冠状动脉旁路移植术后心肌损伤的独立危险因素,而且会增加患者不良心血管事件