三硝基甲苯对大鼠胆固醇和甘油三酯影响的研究

不同剂量的三硝基甲苯(TNT)染毒大鼠,从染毒后第四周开始,各剂量组血清甘油三酯的含量显著下降;从染毒后第六周开始,各剂量组肝脏甘油三酯和胆固醇的含量明显低于对照组,血清胆固醇含量明显高于对照组;至染毒后第八周各指标均未见恢复。表明 TNT 对大鼠的脂代谢有一定的影响。     

2-乙氧基乙醇急性染毒大鼠睾丸和血清某些生化指标的变化

目的观察2-乙氧基乙醇(2-ethoxythanol,EE)急性染毒大鼠睾丸某些酶活力及血清和睾丸中铜、锌含量变化,探讨EE致睾丸损伤的可能机制.方法将90只大鼠随机分为对照组、EE800、1600和3200mg/kg4组,每组20只.将EE用蒸馏水配制成溶液,采取一次性灌胃染毒.于灌胃后第12、24、48和72h,将各组动物随机处死5只,测定睾丸非特异性酯酶、芳基酯酶(ARE)活力及Cu、Zn含量;测定血清Cu、Zn含量及睾丸/体比值.结果染毒后72h,EE800、1600和3200mg/kg组睾丸重量/体重比值分别为0.92、0.87、0.80%,明显低于对照组0.94%(P＜0.05);染毒后12h,EE800、1600和3200mg/kg组睾丸及血清Zn含量分别为21.76、16.96、19.80μmoL/g和1.37、1.35、1.29mg/L,显著低于对照组的33.08μmol/g和1.46mg/L(P＜0.05);在染毒后24h,EE800、1600和3200mg/kg组睾丸Cu和Zn含量分别为1.91、1.91、2.14和22.60、23.75、25.65μg/g,显著高于对照组的1.31和14.μg/g(P＜0.01).结论EE染毒大鼠睾丸重量/体重比值、ARE酶活力及血清Zn含量显著降低而睾丸Zn含量明显升高.推测睾丸可能是EE的靶器官,EE具有明显的睾丸毒性.     

丙烯腈亚急性染毒致大鼠肝损伤及其可能机制探讨

目的研究丙烯腈(ACN)亚急性染毒致大鼠肝组织的损伤作用。方法 60只SPF级健康成年雄性SD大鼠随机分为对照组(玉米油)、低ACN组(11. 5 mg/kg·bw ACN)、中ACN组(23. 0 mg/kg·bw ACN)、高ACN组(46. 0 mg/kg·bw ACN)、N-乙酰半胱氮酸(NAC)干预组(300. 0 mg/kg·bw NAC+46. 0 mg/kg·bw ACN),每组12只,灌胃染毒,1次/d,6 d/周,共28 d。末次染毒结束24 h后,心脏采血,摘取肝,计算肝脏器系数,观察肝组织病理学改变,测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活力,肝组织过氧化氢酶(CAT)活力、谷胱甘肽(GSH)和丙二醛(MDA)含量。结果低ACN组、高ACN组、NAC干预组大鼠肝脏系数高于对照组(P0. 05);低ACN组、高ACN组大鼠血清ALT活力,中ACN组、高ACN组大鼠血清AST活力高于对照组(P0. 05);高ACN组大鼠血清ALT活力高于NAC干预组(P0. 05); ACN各剂量染毒组、NAC干预组大鼠肝CAT活力低于对照组(P0. 05),高ACN组、NAC干预组大鼠肝GSH含量低于对照组(P0. 05),中ACN组、高ACN组、NAC干预组大鼠肝MDA含量高于对照组(P0. 05);高ACN组大鼠肝MDA含量高于NAC干预组(P0. 05);光学显微镜下,对照组大鼠肝小叶结构清晰,肝索排列整齐,肝细胞形态正常;低ACN组与对照组相比无明显异常变化;中ACN组肝细胞轻度疏松,结构清晰;高ACN组肝细胞肿胀,胞浆疏松,核空泡变; NAC干预组较高ACN组大鼠肝组织损伤减轻。结论 ACN亚急性染毒可通过诱导氧化应激使大鼠肝组织脂质过氧化水平发生改变,产生肝损伤作用。     

机体（人与大鼠）接触三硝基甲苯对体内锌铜含量的影响

11名三硝基甲苯作业男工发锌含量显著高于10名非接触男工;而发铜含量则显著低于非接触男工。 大鼠三硝基甲苯(200mg/kg/日)染毒后2周,睾丸锌含量也明显降低,直至染毒后6周皆持续降低。血清锌含量及睾丸铜含量在染毒后6周才出现显著变化。血清铜和肝脏铜锌含量未发现明显改变。     

肌内注射骨折合并脑外伤大鼠血清治疗单纯骨折的放射学及组织形态学观察

目的观察对单纯股骨骨折大鼠肌内注射骨折合并脑外伤大鼠血清(“促骨折愈合血清”)后的放射学及组织形态学变化,以确定该血清是否具备有加速骨折愈合作用。方法 2017年 3月至 2018年 3月,制备骨折合并脑外伤模型 SD大鼠 20只经腹主动脉采血,并分期制备治疗血清;选取 20只健康大鼠提取阴性对照血清,全部加标记并冷藏。应用随机数字表进行分组,每组 32只,分为实验组,对照组及空白组, 96只大鼠均为股骨中段骨折。肌内注射治疗血清用于实验组,肌内注射阴性对照血清用于对照组,空白组肌内注射生理盐水。并于术后第 1周、 2周、 3周、 4周各处死 8只大鼠,利用放射分析比较三组骨折的愈合情况: X射线照射、双能 X线骨密度测量和组织形态学观察。结果术后 X线结果提示实验组骨折愈合进程较对照组、空白组明显加快。测量骨痂体积发现:术后第 2周,实验组骨痂体积( 30.44±2.33)mm3,对照组骨痂体积( 22.68±1.95)mm3,空白组骨痂体积( 21.66±2.35)mm3对照组和空白组骨痂体积明显小于实验组( P＝0.000);术后第 3周,实验组骨痂体积( 26.46± 1.58)mm3对照组骨痂体积( 27.2,9±1.66)mm3空白组骨痂体积( 26.79±2.02)mm3三组骨痂体积比较差异无统计学意义( P＝ 0.669)mm3;术,后 4周,实验组骨痂体积( 22.15±1.,66)mm3对照组骨痂体积( 29.99±1.3,2)mm3空白组骨痂体积( 29.23±1.29)mm3,对照组及空白组骨痂体积明显大于实验组( P＝0.000)。术,后第 1周,实验组骨密度(0.128±0.1,23)mg/cm3对照组骨密度(0.222± 0.121)mg/cm3,空白组骨密度( 0.217±0.103)mg/cm3,对比差异无统计学意义( P＝0.882);术后第 2周,实验,组骨密度( 0.266±0.100)mg/cm3对照组骨密度( 0.208±0.142)mg/cm3空白组骨密度( 0.206±0.302)mg/cm3;术后第 3周,实验组骨密度( 0.218± 0.007)mg/cm3,对照组骨密度( 0.200±0.012)mg/cm3,空白组骨密度( 0.189±0.069)mg/cm3;术后第 4周,实验组骨密度( 0.225±0.009)mg/cm3对照组骨密度( 0.190±0.100)mg/cm3空白组骨密度( 0.202±0.100)mg/cm3;对照组、空白组骨密度第 2周起均低于实验组(P＜0.05,)。骨形态学发现实验组较对照组、,空白组更早形成骨痂,更早出现板层骨,更早进入塑形期。结论脑外伤合并骨折大鼠的血清对骨折愈合有明显的促进作用,为“促骨折愈合血清”应用临床治疗骨科疾患奠定理论基础。     

甲状腺功能低下与亢进大鼠模型的几项生化指标的检测

目的:探讨甲状腺功能低下(甲低)及甲状腺功能亢进(甲亢)模型大鼠的甲状腺功能改变对血钙和血磷的影响。方法:制备甲低及甲亢大鼠模型,测定其血清T3、T4、TSH、钙、磷的含量变化。结果:甲低大鼠血清T3、T4和TSH浓度分别为0.27±0.08nm o l/L、25.87±2.83nm o l/L和3.36±0.42mU/L,与对照组血清T3(0.97±0.11nm o l/L)和T4(68.74±7.57nm o l/L)相比较,均明显降低(P<0.0001),有极显著差异;而血清TSH较对照组TSH含量(1.72±0.43mU/L)显著升高(P<0.0001)。甲亢大鼠T3(9.24±1.56 nm o l/L)和T4(155.73±13.98nm o l/L)含量比对照组均显著升高(P<0.0001),而TSH含量仅为0.37±0.06mU/L,与对照组相比明显降低(P<0.0001)。对照组血钙(C a2+)和血磷(HPO42-)含量分别为2.37±0.30mm o l/L和2.56±0.10mm o l/L;甲低组血钙为2.27±0.15mm o l/L,血磷为2.33±0.10mm o l/L;甲亢组血钙含量为6.17±1.42mm o l/L,血磷含量为3.84±1.13mm o l/L。结论:甲亢大鼠血钙和血磷含量较正常大鼠明显升高。甲低大鼠血清钙、磷含量与对照组大鼠比较均有所下降,但无统计学意义。     

铅镉联合暴露对大鼠肾脏功能损伤的研究

目的 探讨铅、镉对大鼠肾脏功能损伤的联合毒性作用.方法 对大鼠进行铅(300 mgPb/L)、镉(50 mgCd/L)单独和联合(300 mgPb/L 50 mgCA/L)饮水染毒8周.检测尿液中碱性磷酸酶(UALP)、N-乙酰-β-D-氨基葡萄糖苷酶(UNAG)、γ-谷氨酰基转移酶(UGGT)活力和总蛋白(utp)、α-微球蛋白(Ua<,1>-MG)、微量白蛋白(UmAlb)含量的动态变化.结果 单独染毒除2周时Pb、Cd组Ua<,1>-MG含量与Pb组UALP活力外,其余所测指标均从染毒2周开始明显高于对照组(P＜0.05;P＜0.01),且升高幅度与染毒时间呈正相关;联合染毒组从2周开始,所测指标均明显高于对照组(P＜0.01).在整个试验过程中,联合染毒组尿酶活力和尿蛋白含量均高于单独染毒组.结论 Pb、Cd联合暴露对大鼠肾脏功能的损伤呈协同毒性效应.     

黄芪注射液对大鼠肝损伤的保护作用

目的 :探讨黄芪注射液 (HQI)对大鼠实验性肝损伤的保护作用。方法 :采用硫代乙酰胺所致肝损伤模型 ,并测定肝功能 ,肝组织学检查及肝组织血浆和血清脂质过氧化测定。结果 :硫代乙酰胺模型组 2 4 h后大鼠血清 GPT为(1110 .0± 15 2 .5 ) U/10 0 m L,显著高于正常对照组 (P<0 .0 1)。HQI低、中、高剂量组大鼠血清 GPT分别为 (788.3±75 .3) U/10 0 m L、(76 0 .7± 6 7.7) U/10 0 m L、(5 17.1± 6 2 .2 ) U/10 0 m L,均显著低于模型组 (P<0 .0 1)。HQI治疗组肝组织和血清 MDA浓度显著低于模型组 ;病理学改变显著。结论 :HQI0 .5 g/kg～ 4 g/kg可对抗硫代乙酰胺引起的大鼠肝脏损伤 ;本实验结果提示 ,HQI具有减少脂质过氧化物产生的作用     

小檗碱对胰岛素抵抗大鼠糖脂代谢影响的研究

目的研究小檗碱对胰岛素抵抗大鼠糖脂代谢相关指标的影响及其酶学机制。方法选用雄性Wistar大鼠,以高脂高热量饲料喂养8周,复制胰岛素抵抗大鼠模型,造模成功后随机分成模型组、小檗碱组、二甲双胍组,各组干预4周,同时设置健康对照组;比较各组葡萄糖耐量试验(GTT)各时间点血糖水平、总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)、胰岛素敏感性指数(ISI)、肝脏葡萄糖激酶(GK)活性的差异。组间均数比较采用方差分析和LSD-t检验。结果与模型组比较,小檗碱组餐后60min血糖水平下降[分别为(7.2±1.4)mmol/L,(8.0±1.2)mmol/L,P<0.05],FFA水平下降[分别为(258±29)mmol/L,(479±34)mmol/L,P<0.05],ISI增强[分别为(-4.9±0.3),(-5.4±0.4),P<0.05],GK活性增强[分别为(13.6±1.7),(5.6±0.8),P<0.05];二甲双胍阳性对照组取得类似结果。结论小檗碱能调节胰岛素抵抗大鼠的糖脂代谢水平,增强胰岛素敏感性;其调节糖代谢机制可能与提高GK活性水平有关。     

毛兰素通过 JNK/c-Jun信号通路对 2型糖尿病大鼠肝脏损伤的保护作用机制研究

目的基于 c-Jun氨基末端激酶( JNK)/c-Jun信号通路对氧化应激反应的调控作用,研究毛兰素对 2型糖尿病大鼠肝脏损伤的保护作用。方法于 2021年 10月至 2022年 2月腹腔注射链脲佐菌素构建糖尿病大鼠模型,将造模成功大鼠分为模型组、毛兰素低剂量组( 10 mg/kg)、毛兰素高剂量组( 40 mg/kg)及罗格列酮组( 1.25 mg/kg)、毛兰素( 40 mg/kg)+JNK激活组(5 mg/ kg),每组 10只,另取正常饲养大鼠 10只作为对照组。连续给药,6周后,通过血糖仪和胰岛素放射免疫分析试剂盒检测空腹血糖( FBG)、空腹胰岛素( FINS)水平,计算胰岛素抵抗指数( HOMA-IR)及胰岛素敏感指数( ISI);天平称取大鼠体质量和肝质量,计算肝脏指数;试剂盒检测丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶( AST)、总超氧化物歧化酶( T-SOD)、谷胱甘肽过氧化物酶( GSH-Px)活性及丙二醛(MDA)含量; HE染色观察肝脏组织病理学变化; western blotting法检测肝脏组织中 JNK/c-Jun信号通路相关蛋白表达。结果与对照组相比,模型组肝脏指数［( 4.26±0.12)g/100 g比( 2.24±0.09)g/100 g］、 FBG［( 21.49±1.78)mmol/L比( 5.14±0.45)mmol/L］、 FINS［( 80.17±6.38)mmol/L比( 22.35±2.04)mmol/L］、 HOMA-IR［( 76.46±6.56)比( 5.11±1.12)］、 ALT［( 138.71±10.21)U/L比( 70.29±5.54)U/L］和 AST活性［( 77.21±5.08)U/L比( 40.38±3.27)U/L］、 MDA含量［( 13.45±1.34)nmol/mg prot比( 3.72±0.87)nmol/mg prot］、 JNK/c-Jun信号通路相关蛋白表达均明显升高( P<0.05),体质量、 ISI［( ?7.45±0.18)比( ?4.74±0.11)］、 SOD［( 100.79±11.22)U/mg prot比( 223.46±19.86)U/mg prot］和 GSH-Px活性［( 24.42±1.74)U/mg prot比(56.79±3.18)U/mg prot］明显降低( P<0.05),且肝脏组织病理损伤较为严重;与模型组相比,毛兰素低剂量组、毛兰素高剂量组和罗格列酮组肝脏指数、 FBG、FINS、HOMA-IR、ALT和 AST活性、 MDA含量、 JNK/c-Jun信号通路相关蛋白表达均明显降低( P<0.05),体质量、 ISI、SOD和 GSH-Px活性明显升高( P<0.05)减轻肝脏损伤程度;与毛兰素高剂量组相比,毛兰素低剂量组、毛兰素+JNK激活组肝脏指数、 FBG、FINS、HOMA-IR、ALT和 AST活性、 MDA含量、 JNK/c-Jun信号通路相关蛋白表达均明显升高(P<0.05)体质量、 ISI、SOD和 GSH-Px活性明显降低( P<0.05),肝脏损伤恢复缓慢。结论毛兰素可通过调控 JNK/c-Jun信号通路,抑制,JNK/c-Jun通路蛋白表达,从而缓解氧化应激反应,改善糖尿病大鼠肝脏损伤。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.