肾康注射液对高血压肾病大鼠肾脏的保护作用

目的探讨肾康注射液对高血压肾病大鼠肾脏的影响。方法将32只高血压肾病模型大鼠随机分为4组:模型对照组、阳性对照组、肾康注射液大剂量组、肾康注射液小剂量组;WKY大鼠作为阴性对照组。阳性对照组腹腔注射给予福辛普利钠1.6mg·kg-1,肾康注射液大、小剂量组腹腔分别注射给予肾康注射液,相当于生药剂量为4,2g·kg-1,阴性对照组和模型组腹腔分别注射等体积生理盐水,1d1次,连续给药30d。观察肾康注射液对高血压肾病大鼠的尿24h蛋白、尿β2-微球蛋白、肾脏炎症因子以及肾功能、肾脏病变等的影响。结果与模型组比较,肾康注射液能降低大鼠24h尿蛋白的含量及质量浓度,降低肾脏炎症因子白介素-1β(IL-1β),降低尿素氮、血肌酐、尿酸浓度,改善大鼠肾功能,组间比较差异有统计学意义(P<0.05)。结论肾康注射液能改善高血压大鼠肾功能。     

小檗碱对糖尿病肾病大鼠肾组织VEGF表达的影响

目的观察小檗碱(berberine,BBR)对糖尿病肾病(diabetic nephropathy,DN)大鼠肾脏的保护作用。方法采用高糖高脂饲料联合低剂量(35 mg·kg-1)链脲佐菌素(streptozotocin,STZ)诱导糖尿病肾病大鼠模型。随机分为空白对照组、模型组、BBR(50 mg·kg-1)、BBR(100 mg·kg-1)和BBR(200 mg·kg-1)剂量治疗组结果。分别在给药2、4、6、8周时检测大鼠空腹血糖变化,给药8周后测定大鼠血肌酐和尿素氮含量,尿总蛋白含量的变化;PAS染色观察DN肾脏组织病理学改变;免疫组织化学法检测肾脏组织血管内皮生长因子表达;Western blot法检测DN肾脏组织血管内皮生长因子表达水平。结果与正常对照组相比,模型组血糖及尿总蛋白指标明显升高,产生明显的形态学异常变化,同时血管内皮生长因子的表达量明显升高;与模型组相比,小檗碱给药组大鼠血糖和尿总蛋白量均明显下降;同时血液指标血肌酐和尿素氮水平也不同程度的下降;另外,BBR给药组还可明显改善糖尿病肾病大鼠肾脏病理学异常,降低肾脏血管内皮生长因子的表达。结论小檗碱可明显改善糖尿病肾病大鼠发病过程中的生化指标和肾脏病理损伤,这可能与其影响糖尿病肾病状态下肾脏组织中血管内皮生长因子的表达有关。     

水飞蓟素对2型糖尿病肾病大鼠肾脏的保护作用研究

目的：：探讨水飞蓟素对链脲菌素-尼克酰胺诱导的2型糖尿病肾病大鼠肾脏的保护作用。方法：8周龄雄性albino Wist-ar大鼠60只,随机选取45只,采用肌注链脲菌素-尼克酰胺复制2型糖尿病模型(其中3只大鼠复制模型失败),随即分为糖尿病对照组(DC组,n=14)、糖尿病水飞蓟素低剂量治疗组(DT-L,60 mg·kg-1·d-1,n=14)和糖尿病水飞蓟素高剂量治疗组(DT-H,120 mg·kg-1·d-1,n=14)。其余15只大鼠仅注射等体积的缓冲液作为正常对照组(NC,n=15)。模型成功后1周给予水飞蓟素灌胃治疗,持续60 d。采用半自动生化分析仪检测糖化血红蛋白、尿量、血清肌酐、血清尿酸、尿白蛋白水平等生化指标。结果：实验结束时,与NC大鼠比较,DC大鼠的血糖、糖化血红蛋白、尿量、血清尿酸、尿白蛋白等水平均升高(P<0.05)。与DC大鼠比较较,DT-L和DT-H大鼠表现出较低水平的血糖、糖化血红蛋白、尿量、血清肌酐、血清尿酸、尿白蛋白水平,差异有统计学意义(P<0.05)。结论：水飞蓟素对2型糖尿病大鼠的肾脏具有保护作用,为其临床应用奠定实验基础。     

白茅根多糖对IgA肾病大鼠肾组织学病变及血清白细胞介素2和6的影响

目的观察白茅根多糖对IgA肾病大鼠肾组织学病变及血清白细胞介素(IL)2、IL-6含量的影响。方法 50只大鼠随机分为正常对照组、模型组、白茅根多糖低剂量组、白茅根多糖高剂量组和地塞米松组,每组10只。复合免疫法建立IgA肾病大鼠模型,于造模后第9周起白茅根多糖高、低剂量组及地塞米松组分别给予白茅根多糖20 mg·kg-1·d-1、10 mg·kg-1·d-1或地塞米松2 mg·kg-1·d-1,灌胃4周。检测各组大鼠尿红细胞、24 h尿蛋白,血清肌酐(Scr)、尿素氮(BUN)、IL-2、IL-6水平,并观察大鼠肾脏病理学改变。结果大鼠IgA肾病模型造模成功,模型组电镜观察见电子致密物沉积、系膜细胞增生、足突融合明显;尿红细胞数、24 h尿蛋白、血Scr、BUN、IL-6水平、IgA沉积水平均高于正常对照组(P<0.05或P<0.01)。各治疗组与模型组比较,尿红细胞数、24 h尿蛋白水平,血Scr、BUN均明显下降(P<0.01),白茅根多糖高剂量组血清IL-2和IL-6水平低于模型组(P<0.05或P<0.01),肾脏组织病理学异常改善。结论白茅根多糖可改善IgA肾病大鼠肾功能、降低IgA在系膜区的沉积,降低血清IL-2和IL-6水平可能是其作用机制之一。     

雷公藤多苷对糖尿病大鼠肾脏的保护作用及机制

目的观察雷公藤多苷(TWP)对糖尿病大鼠肾脏的保护作用及可能机制。方法用链尿佐菌素腹腔注射法构建糖尿病大鼠模型,动物随机分为正常组、模型组、TWP组(1.8 g.kg-1.d-1灌胃)。于第8周末观察各组大鼠血糖、血肌酐、血尿素氮和24 h尿蛋白量的变化;测定肾组织匀浆超氧化物歧化酶(SOD)活性、肾组织及尿中丙二醛(MDA)含量、血清转化生长因子(TGF-β1)水平;观察肾脏病理形态学的改变。结果 TWP可降低糖尿病大鼠血糖、血肌酐、血尿素氮和24 h尿蛋白水平,能使肾组织和尿MDA含量及血清TGF-β1水平下降,使肾组织SOD活性升高,改善肾脏组织病理学变化。结论雷公藤多苷能明显改善肾脏功能,其机制可能与抑制氧化应激、增强机体抗氧化能力和抑制TGF-β1表达有关。     

联合检测胱抑素C和尿β2-微球蛋白、微量白蛋白在尿酸性肾病早期诊断中的价值

目的:探讨胱抑素C和尿β2-微球蛋白、微量白蛋白在尿酸性肾病早期诊断中的价值。方法:选取120例高尿酸血症患者作为观察组和60例我院职工体检健康医务人员作为对照组,比较两组胱抑素C和尿β2-微球蛋白、微量白蛋白的水平。结果:高尿酸患者血Cys C、尿β2-MG和尿m ALB水平明显高于对照组。联合血胱抑素C、尿β2微球蛋白、尿微量白蛋白诊断尿酸性肾病的阳性率较传统的血清肌酐和血清尿素氮明显增高。结论:联合检测血胱抑素C、尿β?2-微球蛋白和尿微量白蛋白是尿酸性肾病早期诊断的敏感指标,对尿酸性肾病的早期筛查、治疗及预后评估具有重要的价值。     

槲皮素对糖尿病大鼠氧化应激及TGF-β1/CTGF的影响

目的:探讨槲皮素(QE)对糖尿病肾病(DN)大鼠氧化应激及转化生长因子-β1(TGF-β1)/结缔组织生长因子(CTGF)信号通路的影响。方法:腹腔注射链脲佐菌素(STZ)诱导糖尿病模型,模型成功后随机分为3组:糖尿病肾病组(DN组),槲皮素治疗组(QE组,100 mg·kg-1·d-1),卡托普利阳性对照组(CAP组,10 mg·kg-1·d-1)。另设正常对照组(NS组)。治疗12周,观察治疗期间及治疗后大鼠一般状况、血糖、24 h尿白蛋白、肾脏指数、肌酐、尿素氮,测定血清中总抗氧能力(T-AOC)、总超氧化物歧化酶(T-SOD)、丙二醛(MDA)、还原性谷胱甘肽(GSH)的水平;免疫组化方法观察肾皮质中CTGF的表达水平;RT-PCR方法检测肾皮质中TGF-β1mRNA的相对含量;透射电镜观察肾脏超微结构的变化。结果:造模3组均出现糖尿病及肾脏损害,与DN组相比,槲皮素组大鼠血糖、尿白蛋白、肌酐和尿素氮水平明显降低(P<0.01);T-AOC,T-SOD,GSH活性显著提高、MDA水平明显降低(P<0.05,P<0.01);肾皮质CTGF的表达明显减少(P<0.01);肾皮质中TGF-β1mRNA的相对含量明显降低(P<0.01);电镜显示:与DN相比,槲皮素组大鼠系膜细胞增生程度减轻,基底膜厚度均匀,足突融合减轻。结论:槲皮素可提高DN大鼠的抗氧化水平、抑制肾皮质TGF-β1/CTGF的表达,对DN具有防治作用。     

不同剂量和不同给药次数的链脲霉素对大鼠胰岛的影响

目的研究不同剂量和不同给药次数的链脲霉素(STZ)诱发胰岛炎和损害α、β细胞的程度。方法将Wistar大鼠分成6组对照组;A组STZ50mg·kg-1·d-11次给药;B组STZ50mg·kg-1·d-连续2d给药;C组STZ50mg·kg-1·d-1连续3d给药;D组STZ30mg·kg-1·d-1连续5d给药;E组STZ80mg·kg-1·d-11次给药。观察各组大鼠的体重和末梢血糖变化,择期摘取大鼠的胰腺制作成组织切片,进行HE,Azan和免疫组织化学染色,并在光学显微镜下进行组织学比较。结果与对照组相比,各组大鼠的胰腺均存在明显的胰岛炎,D组胰岛的炎细胞浸润、空洞形成和组织纤维化较其他各组显著严重,各组残留胰岛数量、胰岛平均面积、β细胞面积和β细胞面积胰岛平均面积之比均显著减少,尤其是C、D和E组最明显;相反,各组的α细胞面积和α细胞面积胰岛平均面积之比因α细胞的显露而显著增大。结论STZ可同时诱发化学性胰岛炎和自身免疫性胰岛炎,破坏α细胞和β细胞,使胰岛出现空洞形成和组织纤维化。STZ80mg·kg-1·d-11次给药可造成最严重的胰岛损害。     

次黄嘌呤与氧嗪酸钾不同剂量配伍制备高尿酸血症大鼠模型

目的确定次黄嘌呤与尿酸酶抑制剂氧嗪酸钾(OAPS)伍用制备高尿酸血症大鼠模型的合适剂量,为制备持续性高尿酸血症及痛风大鼠模型提供实验依据。方法给大鼠不同配伍剂量的次黄嘌呤(ig)与OAPS(sc)制备代谢性高尿酸血症大鼠模型,于造模后不同时间观察模型大鼠血清尿酸、尿素氮和肌酐水平。结果次黄嘌呤分别为125,250和500mg·kg-1,OAPS以25,50和100mg·kg-1与每个剂量的次黄嘌呤伍用造模。造模后3h血清尿酸和肌酐浓度均有所升高,造模后9h血清尿素氮浓度明显升高。在次黄嘌呤为500mg·kg-1,OAPS为100mg·kg-1时,造模后3,9和12h模型大鼠血清尿酸浓度分别为(781±167),(627±291)和(366±196)μmol·L-1,明显高于正常对照组(86±10),(75±16)和(80±15)μmol·L-1;造模后24h,血清尿素氮和肌酐水平〔(199±96)mg.L-1和(55±16)μmol·L-1〕均明显高于正常对照组〔(61±5)mg.L-1和(21±2)μmol·L-1〕。结论次黄嘌呤500mg·kg-1和OAPS100mg·kg-1伍用制备的代谢性高尿酸血症大鼠模型具有血清尿酸浓度高和维持时间长的特点。     

尿石汤配方颗粒对大鼠草酸钙结石肾脏的保护作用

目的 探讨尿石汤配方颗粒对大鼠草酸钙结石肾脏的保护作用.方法 建立草酸钙大鼠肾结石模型,检测尿石汤不同剂量给药后大鼠血清中肌酐(CRE)、尿素氮(BUN)、Ca2+、Mg2+的变化以及肾脏组织病理变化和肾脏骨桥蛋白(OPN)的表达水平变化.结果 造模后大鼠血清CRE、BUN、Ca2+水平显著升高,Mg2+水平显著下降,...     

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.