羟乙基淀粉130/0.4复苏减轻失血性休克大鼠早期肺损伤的作用

目的通过测定肺组织匀浆中SOD、MDA、MPO的含量、观察肺组织的形态学变化,研究羟乙基淀粉130/0.4复苏对失血性休克大鼠早期肺损伤的影响。方法健康雄性SD大鼠54只,体重230～280g,随机分为3组:对照组(C组)、乳酸林格液复苏组(RL组)、6%羟乙基淀粉130/0.4复苏组(HES组)。按照Wiggers改良法复制失血性休克模型。分别于复苏后1、2、4h测定肺组织中SOD、MDA、MPO的含量;光镜下观察肺组织形态学改变。结果①复苏后RL组与HES组肺组织中MDA的含量逐渐升高,同一时间RL组升高的程度较HES组明显(P<0.01);复苏后RL组与HES组肺组织中SOD的活性逐渐降低,同一时间RL组SOD降低的程度较HES组明显(P<0.01);②复苏后,HES组各时点肺组织MPO含量均明显低于RL组(P<0.01),但高于C组;③免疫组化染色光镜观察显示:RL组肺组织间质水肿、肺泡隔增宽、中性粒细胞侵润程度,HES组比RL组的组织损伤明显减轻。结论 6%羟乙基淀粉130/0.4可以减轻休克及复苏导致的早期肺损伤,是较为理想的休克复苏液体。     

羟乙基淀粉130/0.4不同复苏方案对失血性休克大鼠肺损伤的早期影响及机制

目的探讨不同剂量6%羟乙基淀粉溶液(hydroxyeth-ylstarch,HES)130/0.4和林格液复苏对失血性休克大鼠急性肺损伤(acute lung injury,ALI)的早期影响及机制。方法24只♂SD大鼠,随机分为4组,每组6只:sham组,林格液组(RS组),33mlHES组(H1组),50mlHES组(H2组)。RS组输注3倍失血量的林格液;H1组、H2组分别输注33、50ml的HES130/0.4和一定量的林格液(林格液的量为3倍最大的放血量减去相应剂量的羟乙基淀粉)。测定休克前(T0),复苏前(T1),复苏后2(T4)、3h(T5)血气分析、CD11b和CD18的表达;观察肺组织超微结构变化。结果与T0比较,PaO2RS组T1、H1组T1～5、H2组T5升高;复苏组PaCO2T1～5降低;除H1组外,各液体复苏组pH于T4、5降低。RS组肺组织超微结构受损;H1组除线粒体结构轻微改变外基本正常;H2组核周间隙轻度扩张,粗面内质网轻度扩张,有脱颗粒。各液体复苏组于T1、T4、T5CD11b和CD18的表达增强;与RS组比较,H1、H2组于T4、T5CD11b和CD18的表达降低;与H1组比较,H2组于T4、T5CD11b和CD18的表达增强。结论6%HES130/0.433ml·kg-1复合一定量的林格液复苏可减轻失血性休克大鼠早期肺炎性损伤,其机制与抑制外周血白细胞CDllb和CD18的表达有关。     

万汶在重度子痫前期围术期扩容治疗中的应用

目的：研究第三代人工胶体-中分子低取代级的羟乙基淀粉（万汶）替代白蛋白用于重度子痫前期患者的扩容治疗的有效性及安全性。方法：选择年龄18-45岁,身高145～175cm,体重45～90kg,分娩孕周≥28周,既往无明显内科疾病的重度子痫前期患者共60例。除常规解痉、降压治疗外根据扩容剂的选择将60例患者随即分为万汶组、白蛋白组、空白对照组。对于万汶组及白蛋白纽使用近似剂量的速尿进行利尿治疗。记录患者术前及术后24h、48h、72h、第5天的平均动脉压,口服降压药用量,术后肛门排气时间、水肿消退时间、及平均住院天数,以及出现麻痹性肠梗阻病例数。结果：三组患者的年龄、身高、体重、分娩孕周、术前平均动脉压均元统计学差异,万汶组术后24h及48h内平均动脉压下降较白蛋白组及空白对照组满意,术后降压药拜新同总用量明显低于白蛋白组及空白对照组;三组间的肛门排气时间、水肿消退时间、平均住院天数均有显著性差异,其中万汶组所需时间最短。空白对照组所需时间最长。万汶组无病人出现麻痹性肠梗阻,显著好于另外两组。结论：在速尿的配合下,万汶对用于重度子痈前期围术期的扩容治疗是安全有效的。有利于重度子痫前期患者术后血压的平稳下降、胃肠功能 的恢复、减少降压药的用量及缩短住院时间。     

羟乙基淀粉130/0.4的研究进展

羟乙基淀粉130/0.4是一种新型的羟乙基淀粉代血浆产品, 国外已用于临床.重点综述了羟乙基淀粉130/0.4的扩容作用、药动学、安全性评价和临床研究.     

Na(+)-H(+) exchange blockade, using amiloride, decreases the inflammatory response following hemorrhagic shock and resuscitation in rats

Na⁺–H⁺ exchanger activation on resuscitation following hemorrhagic shock has been shown to result in myocardial injury and dysfunction. Amiloride, an inhibitor of the Na⁺–H⁺ exchanger has been shown to protect the myocardium against reperfusion injury in the ischemic hearts. However, the mechanism of protection remains unclear. Na⁺–H⁺ exchanger blockers have been implicated in the regulation of inflammatory responses and chemokine production. The present study investigated the therapeutic anti-inflammatory value of amiloride on myocardial contractile function in post-resuscitation following hemorrhagic shock in rats. Male Sprague–Dawley rats were assigned into 3 groups: 1) hemorrhage, 2) hemorrhage treated with amiloride, and 3) sham hemorrhage (n = 6 per group). Rats were hemorrhaged over 60 min to reach a mean arterial blood pressure of 40 mm Hg. After 60 min of hemorrhagic shock, rats were treated or not by injection of 1 ml of 100 μM amiloride (0.027 mg/ml) intra-arterially. Resuscitation was made in vivo by reinfusion of the shed blood to restore norm tension for 30 min. Left ventricular contractile function was measured in the isolated hearts following hemorrhage and in vivo resuscitation using the Langendorff apparatus. Arterial blood samples were collected from all groups at the end of the experimental period (90 min) for cytokine measurements (TNF-α). Amiloride decreased the inflammatory response to hemorrhagic shock and resuscitation by lowering the levels of TNF. These results indicate that amiloride protects the myocardium by down regulating the inflammatory response to hemorrhagic shock and resuscitation.     

Farnesol prevents Fe-NTA-mediated renal oxidative stress and early tumour promotion markers in rats

Excess iron deposition in tissues leads to organ dysfunction and impairment. In this study, the protective effects of farnesol (FL), an isoprenoid, against Fe-NTA (9 mg iron/kg body weight i.p.)-induced oxidative damage and early tumour promotion markers are evaluated. The pretreatment of iron-intoxicated rats with 1% and 2%/kg body weight oral dose of FL for 7 consecutive days significantly reversed the iron-induced increase in H2O2 content (P < 0.001), malondialdehyde formation, xanthine oxidase activity (P < 0.001), ornithine decarboxylase activity (P < 0.001) and 3[H]thymidine incorporation in renal DNA (P < 0.005) with simultaneous significant depletion in serum toxicity markers blood urea nitrogen (BUN) and creatinine (P < 0.001). Significant dose-dependent restoration was recorded in renal glutathione content, its dependent enzymes and other phase II metabolizing enzymes viz., catalase, glutathione-S-transferase and quinone reductase (P < 0.001) with prophylactic treatment of FL. Present results support that FL markedly lowers the oxidative damage and appearance of tumour markers, which precludes its development as a chemopreventive tool.     

白藜芦醇抑制人牙龈成纤维细胞炎症和氧化应激的机制研究

目的 探讨白藜芦醇（RSV）对牙龈卟啉单胞菌脂多糖（LPS）诱导的人牙龈成纤维细胞（HGF）的炎症和氧 化应激的调节作用。方法 原代培养HGF,将细胞分为实验1和实验2：实验1细胞分为对照组、LPS组、RSV 20 μmol/L 组、RSV 40 μmol/L组、RSV 80 μmol/L组、LPS+RSV 20 μmol/L组、LPS+RSV 40 μmol/L组和LPS+RSV 80 μmol/L组;实 验2细胞分为对照组、LPS组、LPS+RSV 40 μmol/L 组、LPS+RSV 40 μmol/L+E5564组和LPS+E5564组。通过CCK-8 法评估细胞活力。利用酶联免疫吸附试验测定白细胞介素（IL）-1β、IL-6、IL-8、肿瘤坏死因子（TNF）-α、超氧化物歧 化酶（SOD）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）水平。通过Western blot分析测量蛋白的表达水平。结 果 20、40和80 μmol/L RSV对HGF均没有明显的细胞毒性作用。在LPS诱导的HGF细胞中,40和80 μmol/L RSV 通过下调IL-1β、IL-6、IL-8和TNF-α的表达减弱炎症反应,降低了MDA的含量,并显著提高了SOD的水平,80 μmol/L RSV显著提高了GSH-Px水平（P＜0.05）。此外,20、40和80 μmol/L RSV可诱导Toll样受体4（TLR4）/MyD88/NF-κB 信号通路的失活,其均可降低TLR4、MyD88和p-p65蛋白的表达水平（P＜0.05）。TLR4抑制剂（E5564）通过下调IL- 1β、IL-6、IL-8和TNF-α的产生以及上调GSH-Px水平进一步增强了RSV对炎症和氧化应激损伤的缓解作用（P＜ 0.05）。结论 RSV可通过诱导TLR4/MyD88/NF-κB信号通路失活,减轻LPS导致的HGF炎症和氧化应激损伤。     

羟乙基淀粉130／0．4氯化钠注射液应用评价及文献回顾

目的通过分析我院羟乙基淀粉130／0．4氯化钠注射液（HEs）使用情况,评价其使用的安全合理性,为临床应用及防范不良反应发生提供依据。方法回顾性分析2013年9月份我院使用过羟乙基淀粉130／0．4氯化钠注射液（HES）的住院患者用法用量,适应证、禁忌证、用药前后肾功能、凝血功能变化等指标。结果不良反应包括19例肾功能损害,16例凝血功能障碍。结论HES使用存在肾损害和凝血障碍风险,临床医师应严格遵循FDA建议,规范HES的使用,防范不良反应的发生。     

Gastric oxidative stress and hemorrhagic ulcer in Salmonella typhimurium-infected rats

Infection of Salmonella typhimurium (Salmonella typhi) can lead to various organ diseases. This research first proposed that Salmonella typhi-infection could result in gastric oxidative stress and hemorrhagic ulcers that were ameliorated by ofloxacin, lysozyme chloride and several antioxidants, including exogenous glutathione (GSH), allopurinol and dimethylsulfoxide (DMSO). Male Wistar rats were given intrajejunally the live culture of Salmonella typhi [1 x 10(10) colony-forming unit (CFU)/rat] and followed by deprivation of food for 36 h. Age-matched control rats received vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or a simulated gastric juice containing 100 mM HCl, 17.4 mM pepsin and 54 mM NaCl. Infection of Salmonella typhi produced an aggravation of ulcerogenic factors, including enhancing gastric acid back-diffusion, mucosal lipid peroxide generation and hemorrhagic ulcer as well as an attenuation of mucosal GSH level. Intragastric irrigation of gastric juice caused further aggravation of these gastric biochemical parameters. This exacerbation of ulcerogenic factors was abolished by pretreatment of ofloxacin and lysozyme chloride. Antioxidants, such as reduced GSH, allopurinol and DMSO also produced significant (P<0.05) amelioration of gastric damage in Salmonella typhi-infected rats. In conclusion, infection of Salmonella typhi substantially caused gastric oxidative stress and disruption of gastric mucosal barriers, consequently resulted in gastric hemorrhagic ulcerations that were effectively ameliorated by ofloxacin, lysozyme chloride and various antioxidants.     

高效离子排斥色谱法测定羟乙基淀粉130/0.4电解质注射液中醋酸盐的含量

目的:建立高效离子排斥色谱法测定羟乙基淀粉130/0.4电解质注射液中醋酸盐的含量。方法:采用ICSep ICE-ORH-801(6.5 mm×300 mm,5μm)色谱柱,流动相为0.005 mol·L-1硫酸,流速为1.0 mL·m in-1,柱温为60℃,检测波长210nm。结果:醋酸钠进样量在2.0～16.0μg范围内线性关系良好(r=0.9993);平均回收率(n=9)为99.03%,RSD为0.22%。结论:本分析方法简便、准确,可作为羟乙基淀粉130/0.4电解质注射液中醋酸钠的定量分析方法。     

Benidipine prevents oxidative stress,inflammatory changes and apoptosis related myofibril damage in isoproterenol-induced myocardial infarction in rats

Abstract

Objective: The effects of benidipine on oxidative stress and myocardial apoptosis were assessed in isoproterenol (ISO)-induced myocardial infarction (MI) in wistar rats.

Materials and method: Animals were pretreated with benidipine (1, 3, 10?μg/kg/day Body weight) intravenously for a period of 28 days. After pretreatment, ISO (85?mg/kg Body weight, subcutaneous) was injected in rats at an interval of 24?h to induce MI. Myocardial oxidative stress, cardiac biomarkers, apoptosis, inflammatory mediators, and ultrastructural architecture of the cardiac tissue were assessed in ISO-induced MI in rats.

Result: Significant variation in the level of TBA, antioxidant enzymes (GSH, CAT, SOD, GPx, GRx, GST) in myocardium, cardiac biomarkers (CK-MB, LDH) in serum, Caspase-3, C-reactive protein (CRP), and alteration in ultrastructural architecture of cardiac tissue confirmed the cardiotoxicity induced by ISO. Pretreatment with benidipine preserved the lipid peroxide and antioxidant enzymes, and furthermore showed maintained levels of myocardial biomarker, CRP and caspase-3. Ultrastructure architecture of cardiac tissue was also found to be well preserved.

Conclusion: The present study suggested cardioprotective effect of benidipine which may possibly be due to its antioxidant activity and antiapoptotic nature.     

Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries in rats

We aimed to evaluate the effect of natural antioxidant crocin in alleviating hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin during resuscitation. Mortality at 12 h and 24 h post resuscitation was documented. HS and resuscitation induced organ injuries, as characterized by elevated wet/dry ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate aminotransferase and alanine aminotransferase, whereas rats received crocin treatment demonstrated improvements in all the above characteristics. This protective effect coincided with reduced malondialdehyde and increased glutathione in both serum and lung tissues, indicating attenuated oxidative stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver were also reduced. Crocin can potentially be used to protect organs from HS-induced damages during resuscitation due to its anti-oxidative role.     

大蒜素对慢性肾衰大鼠氧化应激和炎症反应的影响

目的研究大蒜素对慢性肾衰(Chronic renal failure,CRF)大鼠肾脏组织氧化应激损伤和炎症反应的影响。方法 100只实验用大鼠随机分为正常对照组,模型对照组,大蒜素5、10、20 mg/(kg·d)组,采用腺嘌呤溶液250 mg/(kg·d)灌胃21 d的方法建立CRF大鼠模型,大蒜素5、10、20 mg/(kg·d)组腹腔注射给药治疗,疗程为28 d。测定24 h尿量、24 h尿蛋白量及血清肾功能指标(BUN、SCr、UA含量),计算肾脏指数;HE染色观察肾脏组织病理变化;化学比色法测定肾脏组织匀浆中抗氧化酶活性和丙二醛(MDA)含量,血清中总抗氧化能力(T-AOC)和晚期氧化蛋白产物(AOPPs)水平;ELISA法测定血清炎症细胞因子C反应蛋白(CRP)、白细胞介素(IL)-1、IL-6、肿瘤坏死因子-α(TNF-α)、可溶性细胞间黏附分子-1(sICAM-1)、血管间黏附分子-1(VCAM-1)的水平。结果与模型对照组比较,大蒜素10、20 mg/(kg·d)组24 h尿量减少、24 h尿蛋白量降低(P<0.05或P<0.01),肾脏指数降低(P<0.01),血清BUN、SCr、UA含量降低(P<0.05或P<0.01)。大蒜素治疗明显改善CRF大鼠肾脏组织病变。大蒜素10、20 mg/(kg·d)组肾脏组织超氧化物歧化酶(SOD)活性升高,但MDA、血清AOPPs水平降低(P<0.05或P<0.01);20 mg/(kg·d)组肾脏组织过氧化氢酶(CAT)活性和血清T-AOC水平均升高(P<0.05)。大蒜素10、20 mg/(kg·d)组血清CRP、TNF-α、sICAM-1、VCAM-1含量降低(P<0.05或P<0.01);20 mg/(kg·d)组IL-1、IL-6含量显著降低(P<0.05或P<0.01)。结论大蒜素可能通过抑制肾脏组织氧化应激损伤和炎症反应而对CRF大鼠起到一定的保护作用。     

早期肠内营养对休克后患者炎性反应的疗效研究

目的 研究早期肠内营养(EN)对休克患者内毒素及肿瘤坏死因子-α(TNF-α)的作用及全身炎性反应综合征(SIRS)的影响.方法 休克67例随机分为早期EN组和肠外营养(TPN)组,检测两组患者肠内营养治疗前、治疗后1、3、5 d血浆中内毒素与TNF-α水平;统计两组SIRS的持续时间与多器官功能障碍(MODS)的发生...     

七氟醚后处理对失血性休克复苏大鼠海马氧化应激及SIRT1/PGC-1α表达的影响

目的探讨七氟醚后处理对失血性休克复苏大鼠海马氧化应激,以及对沉默信息调节因子1 (silent information regulation 1,SIRT1)和过氧化物酶体增殖物激活受体γ共激活因子1α(peroxisome proliferator-activated receptorγcoactivator-1α,PGC-1α)表达的影响。方法♂SD大鼠随机分为假手术组(Sham组)、失血性休克复苏组(Shock组)、七氟醚后处理组(Sevo组)。Sevo组经失血性休克后,于血液回输即刻吸入2.4%七氟醚,Sham组和Shock组在相应时间点吸入95%O_2,5%CO_2混合气体,记录放血即刻(T0)、放血结束即刻(T1)、血液回输即刻(T2)和血液回输结束即刻(T3)的平均动脉压(MAP),并采集动脉血进行血气分析。血液回输结束24 h后,检测海马组织丙二醛(MDA)含量和线粒体超氧化物歧化酶(SOD)活性,Western blot测定海马组织中SIRT1和PGC-1α蛋白的表达。结果与Sham组相比,Shock组MDA含量增加,SOD活性降低,SIRT1和PGC-1α蛋白表达上调(P<0.05);与Shock组相比,Sevo组MDA含量减少,SOD活性增强,SIRT1和PGC-1α蛋白表达上调(P<0.05)。结论七氟醚后处理可减轻失血性休克复苏大鼠海马氧化应激,其机制可能与上调SIRT1和PGC-1α的蛋白表达水平有关。     

Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion

Agonists of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) exert protective effects in several models of ischemia/reperfusion injury, but their role in stroke is less clear. The study investigates the effects of two PPAR-gamma agonists, rosiglitazone and pioglitazone, on oxidative stress and inflammatory response induced by ischemia/reperfusion in the rat hippocampus. Common carotid artery occlusion for 30 min followed by 1 h reperfusion resulted in a significant increase in the generation of reactive oxygen species, nitric oxide and the end products of lipid peroxidation as well as markedly reduced endogenous antioxidant glutathione levels and up-regulated superoxide dismutase activity. Western blot analysis showed that ischemia/reperfusion lead to an increase in cyclooxygenase-2 (COX-2) expression, as well activating p38 and p42/44 mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB). Pre-treatment with either rosiglitazone or pioglitazone significantly reduced oxidative stress, COX-2 protein expression and activation of MAPKs and NF-kappaB. Taken together, the results provide convincing evidence that PPAR-gamma agonists exert protective effects in a rat model of mild forebrain ischemia/reperfusion injury by inhibiting oxidative stress and excessive inflammatory response.