三氧化钨纳米方块致小鼠肝脏和肾脏的急性氧化损伤

目的为探讨WO3纳米方块对小鼠肝脏和肾脏组织的急性氧化损伤作用。方法将42只Balb/c小鼠随机分为7组,每组6只,分别为5、10、20、40、80、160 mg/kg的WO3纳米方块染毒组和生理盐水对照组。灌胃染毒7 d后测定肝脏和肾脏组织中活性氧(ROS)、还原性谷胱甘肽(GSH)以及丙二醛(MDA)的含量。结果随着WO3纳米方块染毒剂量的升高,肝脏和肾脏组织的ROS和MDA的含量均呈逐渐上升的趋势,而GSH含量呈逐渐降低的趋势,各指标均呈一定的剂量-效应关系。剂量≥20 mg/kg时肝脏组织ROS含量和剂量≥10 mg/kg时肾脏组织ROS含量分别与对照组比较,差异有统计学意义(P<0.05);剂量≥20 mg/kg时,肝脏和肾脏组织MDA含量与对照组比较,差异有统计学意义(P<0.05);剂量≥40 mg/kg时肝脏组织GSH含量和剂量≥20 mg/kg时肾脏组织GSH含量分别与对照组比较,差异有统计学意义(P<0.05)。结论一定剂量的WO3纳米方块能够对小鼠肝脏和肾脏造成急性氧化损伤。

桉叶多酚对大鼠乙醇急性氧化损伤保护作用的研究

为了评价桉叶多酚对昆明大鼠体内乙醇急性氧化损伤的保护效果,本文以桉叶多酚饲喂昆明大鼠,以乙醇灌喂大鼠进行急性氧化损伤造模,对血液和肝脏总抗氧化能力、各抗氧化蛋白酶活性和肝脏组织病变情况进行检测。结果显示:体内总抗氧化能力提升,其中血清最高增强33.12%,肝脏最高增强56.83%;能有效降低体内MDA的含量,其中血清最高降低23.89%,肝脏最高降低50.73%;T-SOD活性有一定程度增强;实验组GSH-Px活性有所降低,但是给药组与阳性对照组无差异;肝脏切片观察发现,三个给药组肝脏组织的细胞排列规则,不规则空泡减少,肝小叶炎性细胞浸润较少,少见有局部坏死灶的出现,表明乙醇急性氧化损伤受到抑制,肝脏组织得到保护。综合所述,桉叶多酚具有体内抗氧化保护作用,这为桉叶多酚作为抗氧化剂的应用提供了研究基础。

乙醇摄入对乙醛脱氢酶2不同基因型小鼠急性心肌梗死及DNA氧化损伤的影响

目的探讨大剂量乙醇摄入对乙醛脱氢酶2(ALDH2)不同基因型小鼠急性心肌梗死及DNA氧化损伤的影响。方法将23只ALDH2基因敲除型(KO)和19只野生型(WT)小鼠随机分为4组:KO组11只,KO+乙醇(E)组12只,WT组9只,WT+E组10只,其中KO+E组及WT+E组经口灌胃大剂量乙醇[2g/(kg·d),连续8d],而KO组及WT组每日经口予以等量0.9%氯化钠溶液连续8d。所有小鼠均制备急性心肌梗死模型,建模4周后经超声诊断仪检测心功能,采用伊文蓝颜料测定心肌梗死面积,E LISA法测定心肌8-羟基脱氧鸟苷(8-OHdG)水平。结果(1)急性心肌梗死造模后4周,KO组、KO+E组、WT组、WT+E组小鼠存活数量分别为7、8、7、7只,病死率分别为18.2%、33.3%、22.2%、30.0%,4组间差异无统计学意义(P>0.05)。(2)WT组小鼠左室短轴缩短率、射血分数均高于KO组小鼠,4组间差异均有统计学意义(均P<0.05)。(3)心肌梗死面积由大至小依次为:KO+E组>KO组>WT+E组>WT组,4组间差异均有统计学意义(均.P<0.05)。(4)心肌8-OHdG水平由高至低依次为:KO+E组>KO组>WT+E组>WT组,4组间差异均有统计学意义(均P<0.05)。结论增强ALDH2表达可有效地拮抗大剂量乙醇摄入对急性心肌梗死的损害作用,其发挥保护作用的机制可能与减轻心肌细胞DNA氧化损伤有关。

生脉饮对内毒素诱导急性肺损伤大鼠一氧化氮及其合酶的影响

目的:探讨一氧化氮(NO)和诱生型一氧化氮合酶(iNO S)在脂多糖(LPS)诱导大鼠急性肺损伤(AL I)中的作用及生脉饮对其的影响。方法:雄性W istar大鼠按随机数字表法分为对照组、AL I组、生脉饮组、地塞米松组。舌下静脉注射LPS复制AL I模型。观察大体标本、组织病理以及肺湿/干重比、支气管肺泡灌洗液中中性粒细胞比、蛋白含量、肺毛细血管通透性和肺泡通透性指数等生物学指标。测定血浆NO和肺组织匀浆iNO S活性。结果:与对照组比较,AL I组肺组织病理显示肺间质及肺泡有明显的损伤和细胞浸润,各生物学指标及NO和iNO S显著升高(P<0.05或P<0.01);与AL I组比较,地塞米松组和生脉饮组肺组织病理明显减轻,各生物学指标及NO、iNO S也相应下降(P<0.05或P<0.01)。结论:地塞米松和生脉饮两种药物对LPS诱导的AL I具有保护作用,其机制可能是通过抑制NO水平和iNO S活性实现。

基于网络药理学探讨莱菔硫烷治疗急性一氧化碳中毒脑损伤的作用机制

目的:基于网络药理学方法,探究莱菔硫烷(SFN)治疗急性一氧化碳中毒(ACOP)脑损伤潜在靶点和分子机制。方法:检索Pubchem数据库获得SFN的2D结构,通过Pharmmapper网站获得化合物预测靶点,检索GeneCards和OMIM数据库获得ACOP脑损伤的靶点,通过STRING数据库构建蛋白质相互作用(PPI)网络,利用Cytoscape软件构建分子网络,应用Metascape数据库进行GO和KEGG分析。结果:通过筛选,共获得SFN的有效靶基因81个,ACOP脑损伤有效靶基因1207个,其中共同靶点36个,PPI网络分析显示ALB、AKT1、MMP9等为网络的核心靶点,GO分析结果提示相关靶点显著富集在细胞对肽的反应、对氧化应激的细胞反应以及活性氧代谢过程的正向调节等生物功能,KEGG富集分析结果主要涉及癌症通路、乙型肝炎通路、催乳素信号通路、自噬-动物信号通路等相关通路。结论:通过网络药理学初步揭示SFN对ACOP脑损伤的作用具有多靶点性,SFN作用于ALB、AKT1、MMP-9等核心靶点,通过抗炎、抗细胞凋亡、增强自噬等发挥抗ACOP作用。

桂花提取物对雄性果蝇抗氧化及抗衰老作用的研究

研究桂花提取物对雄性果蝇体内抗氧化及应激状态下抗衰老的作用。乙醇提取桂花,减压浓缩后得桂花醇提物,收集2 d龄雄性果蝇成虫,随机分为对照组、桂花提取物剂量组(2.5、5、10、15 mg/mL)共5组,进行雄性果蝇的生存实验和应激实验,测定平均寿命、最高寿命绘制生存曲线及体内蛋白质,超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)和丙二醛(malondialdehyde,MDA)等抗氧化酶活力活性。桂花提取物10、15 mg/mL剂量能极显著延长雄性果蝇的寿命(P<0.01);15 mg/mL能显著提高45 d龄果蝇体内血清总蛋白(total protein,TP)含量(P<0.05);10、15 mg/mL剂量组能显著增加25 d龄果蝇体内CAT活性(P<0.05),所有剂量组能极显著增加45 d龄果蝇体内CAT活性(P<0.01);5 mg/mL能显著降低25 d龄果蝇体内MDA含量(P<0.05),10、15 mg/mL剂量组能极显著降低25 d龄果蝇体内MDA含量(P<0.01),10 mg/mL剂量组能显著降低45 d龄果蝇体内MDA含量(P<0.05),15 mg/mL剂量组能极显著降低45 d龄果蝇体内MDA含量(P<0.01);5、10、15 mg/mL剂量组能极显著增加25 d龄和45 d龄果蝇体内SOD活性(P<0.01)。桂花提取物可以提高SOD、CAT等抗氧化应激酶活性,可以缓解机体衰老引起的氧化应激产生的自由基对机体的损伤,具有延长寿命的作用。

The Hepatoprotective Effects of Solanum Incanum on Acetaminophen-lnduced Hepatotoxicity in Guinea Pigs

Solanum incanum, a shrubby herb, is widely distributed and used as analgesic, antitoxic, and antispasmodic in folk medicine. In the present study, the protective effects of aqueous extract of S. incanum against acetaminophen induced acute liver damage were evaluated in guinea pigs. Animals were orally administered with S. incanum extract （50 and 100 mg/ kg bw） and silymarin （ 100 mg / kg bw） respectively for 6 days followed by acetaminophen administration （2 g / kg bw） at the 7th day. The results showed that the treatment with S. incanum extract significantly lowered the acetaminophen-induced serum levels of hepatic marker enzymes （AST, ALT, and ALP）, Liver histopathology also showed that S. incanum extract reduced the incidence of liver lesions including the swelling of hepatic cells, lymphocytes infiltration, nucleus condensation, and hepatic necrosis induced by acetaminophen treatment in guinea pigs. The S. incanum extract at a dose of 100 mg / kg bw was more effective in suppressing the oxidative damage than the extract at a dose of 50 mg / kg bw. Therefore, the results of this study suggest that S. incanum extract could protect liver against the acetaminophen-induced oxidative damage.

Protective effects of Polygonatum sibiricum against CCl_(4)-induced acute liver injury in rats through oxidative stress and mitochondrial apoptotic pathways

In the present study,we aimed to investigate the hepatoprotective effect of Chinese herbal medicine Polygonatum sibiricum(PS).In this study,a rat acute liver injury(ALI)model was established by a single intraperitoneal injection of 50%CCl_(4) oil solution,and the rats were treated intragastrically with Polygonatum sibiricum aqueous extract(PSAE).The results showed that PSAE significantly decreased the serum levels of ALT,AST and ALP,increased the activities of glutathione(GSH)and superoxide dismutase(SOD),decreased malondialdehyde(MDA)activity in hepatic tissue,and decreased the reactive oxygen species(ROS)level in hepatocytes.The expressions of Nrf2,NQO-1,HO-1,Bcl-2,Bcl-x L mRNA,and HO-1 proteins were elevated,and the expression of p53 mRNA was decreased.In conclusion,PSAE exerted a powerful protective action against CCl_(4)-induced ALI in rats via effectively regulating the expressions of Nrf2-Keap1-ARE related genes and proteins,and inhibiting hepatocyte apoptosis.These outcomes provided evidence that PS had apparent hepatoprotective effect.

Early changes of endothelin,nitric oxide and arginine-vasopressin in patients with acute cerebral injury

Objective: To investigate the early changes and clinical significance of plasma endothelin (ET), nitric oxide (NO) and arginine vasopressin (AVP) in patients with acute moderate or severe cerebral injury. Methods: The early (at 24 hours after injury) plasma concentrations of ET, NO and AVP were measured with radioimmunoassay and Green technique in 48 cases of acute moderate (GCS≤8 in 27cases ) or severe (GCS>8 in 21 cases) cerebral injury (Group A), in 42 cases of non cerebral injury (Group B) and in 38 normal individuals (Group C), respectively. Results: The early plasma concentrations of ET ( 109.73 ng/L±12.61 ng/L ), NO ( 92.82 μmol/L± 18.21 μmol/L ) and AVP ( 49.78 ng/L±14.29 ng/L ) in Group A were higher than those in Group B ( 67.90 ng/L ±11.33 ng/L , 52.66 μmol/L±12.82 μmol/L and 29.93 ng/L±12.11 ng/L , respectively, P<0.01 ) and Group C ( 50.65 ng/L±17.12 ng/L , 36.12 μmol/L ±12.16 μmol/L and 5.18 ng/L ± 4.18 ng/L , respectively, P<0.001 ). The amounts of ET, NO and AVP in patients with severe cerebral injury were 116.18 ng/L± 18.12 ng/L , 108.19 μmol/L±13.28 μmol/L and 58.13 ng/L±16.78 ng/L , respectively, which were significantly higher than that of the patients with moderate cerebral injury ( 92.33 ng/L±16.32 ng/L , 76.38 μmol/L ±12.71 μmol/L and 36.18 ng/L±12.13 ng/L respectively, P<0.01 ). The early levels of ET, NO and AVP in Group A were negatively related to the GCS scales. The amounts of ET, NO and AVP were 126.23 ng/L± 15.23 ng/L , 118.18 μmol/L±10.12 μmol/L and 63.49 ng/L±14.36 ng/L respectively in patients with subdural hematoma, which were significantly higher than those in patients with epidural hematoma ( 81.13 ng/L ±12.37 ng/L , 68.02 μmol/L±13.18 μmol/L and 45.63 ng/L±12.41 ng/L respectively, P<0.01 ). The plasma concentrations of ET, NO and AVP in stable duration (at 336 hours after injury) in Group A and Group B were similar to those in Group C. Conclusions: ET, NO and AVP were related to the pathophysiological process that occurs in the early stage of acute cerebral injury and the values of ET, NO and AVP correlate positively with the clinical manifestations. The changes of plasma ET, NO and AVP can be regarded as important indices to assess the severity of acute cerebral injury.

3,4-Dihydroxyacetophenone alleviates lipopolysaccharide-induced acute lung injury as a potential anti-inflammatory and anti-oxidative agent

Enhanced inflammatory response and oxidative stress cause acute lung injury(ALI). Controlling inflammation and oxidation can ameliorate ALI. In the present study, we aimed to determine whether 3,4-Dihydroxyacetophenone(compound 1)could ameliorate lipopolysaccharide(LPS)-induced ALI by suppressing inflammation and oxidation. In this study, compound 1 reduced LPS-induced inflammatory cytokines and oxidative stress in RAW 264.7 cells. Moreover, compound 1 suppressed the expression of inflammatory protein p65, inhibited IkBα phosphorylation, decreased the nuclear translocation of p65, and increased the expressions of anti-oxidative protein nuclear factor erythroid 2-related factor 2(Nrf-2) and heme oxygenase-1(HO-1), which was reduced by LPS, in leukemia cells in mouse macrophage(RAW 264.7) cells. Furthermore, compound 1 could also ameliorate LPS-induced ALI in vivo, with a reduction of inflammatory cytokines, oxidative stress, and nuclear factor-kappa B(NF-κB)signaling pathway activation. This study emphasized the anti-inflammatory and anti-oxidative activities of compound 1, which could be a valuable therapeutic agent against ALI.

Study of the effects of mild hypothermia on cerebral PO_2, PCO_2 and pH and body temperature in patients with acute severe head injury

Objective: To study the effects of mild hypothermia on cerebral oxygen partial pressure, carbon dioxide partial pressure, pH and body temperature （PbrO2, PbrCO2, pHbr and BT） in patients with acute severe head injury. Methods: Thirty-eight patients with acute severe head injury were treated with mild hypothermia, meantime PbrO2, PbrCO2, pHbr and BT were monitored in order to study the changes of PbrO2, PbrCO2, pHbr and BT. Results: In patients with acute head injury, mild hypothermia obviously increased PbrO2, decreased PbrCO2 and CO2 accumulation and acidosis in brain tissue. BT was 1℃-（1.5）℃ higher than rectal temperature（RT） after injury. The BT and RT were decreased when the patients were treated with mild hypothermia, but at the same time the difference between BT and RT was increased. Conclusions: In patients with acute severe head injury the direct monitoring of PbrO2, PbrCO2, pHbr and BT was safe and reliable, and is helpful in estimating prognosis and mild hypothermia therapy.

Protection of carbon monoxide-releasing molecule against lung injury induced by limb ischemia-reperfusion

Objective： To observe the role and mechanism of CO- releasing molecule （CORM）-2 in lung injury induced by ischemia-reperfusion （IR） of hind limbs in rats. Methods： Arat model of lung injury induced by IR of hind limbs was established. A total of 40 Sprague Dawley （SD） rats were randomly divided into 5 groups （n = 8）： sham, sham ＋ CORM-2, IR, IR ＋ CORM-2 and IR ＋ dimethyl sulfoxide （DMSO）. Rats in the IR group received hind limb ischemia for 2 hours and reperfusion for 2 hours, rats in the sham group underwent sham surgery without infrarenal aorta occlusion, rats in the IR＋CORM-2 group and in the sham ＋ CORM-2 group were given CORM-2 （10 μmol/kg intravenous bolus） 5 minutes before reperfusion or at the corresponding time points, while rats in the IR ＋ DMSO group was treated with the same dose of vehicle （DMSO） at the same time. The lung tissue structure, polymorphonuclear neutrophil （PMN） count, wet-to-dry weight ratio （W/D）, malondialdehyde （MDA） content, myeloperoxidase （MPO） activity, intercellular adhesion molecule- 1 （ICAM- 1）expression, I κBα degradation and nuclear factor （NF）-κB activity in the lungs were assessed. Results： As compared with the sham group, lung PMNs number, W/D, MDA content, MPO activity, ICAM-1 expression and NF- κB activity significantly increased in the IR group, but the level of I κBα decresed （P〈0.01）. Compared with the IR group, lung PMNs number, W/D, MDA content, MPO activity and ICAM- 1 expression significantly decreased in the IR＋COMR-2 group （P〈0.01）, while the level of IκBα increased. Conclusions： These data demonstrate that CORM-2 attenuates limb IR-induced lung injury through inhibiting ICAM-1 protein expression, NF-κB pathway and the leu- kocytes sequestration in the lungs following limb IR in rats, suggesting that CORM-2 may be used as a therapeutic agent against lung injury induced by limb IR.