三氧化二砷、黄磷、四氯化碳的急性肝脏毒作用的研究

大鼠每日分别经口染毒三氧化二砷（45mg/kg)、黄磷（3mg/kg)、四氯化碳（990mg/kg)，连续4日后，均出现肝脏病理改变，黄磷及四氯化碳组大鼠的血清GPT和GOT活性明显升高，但三氧化二砷组则无显著变化，三个染毒组大鼠的血清和肝微粒体过氧化脂质含量、血清IgM和补体C3含量均较对照组显著升高。     

氰戊菊酯对肺脏与外周血的影响

本文报道经气管染毒氰戊菊酯对大鼠肺脏和外周血的影响。氰戊菊酯引起肺实质损伤和异常的血清反应具有明显的剂量依赖性以及典型的时间反应特征;PAMs、PMN、LDH、NANA和ALb是早期灵敏的生物学评价指标;BALF中酶活性升高和蛋白含量增加,主要来自肺细胞生物膜的损伤和肺气血/屏障破坏后的血浆渗出;PAMs体外吞噬杀菌功能的下降,主要与其胞膜及亚微结构损伤有关。     

藏药七十味珍珠丸灌胃给予脑缺血再灌注损伤模型大鼠的量-时-效关系研究

目的:研究七十味珍珠丸治疗大鼠脑缺血再灌注损伤的量-时-效关系。方法:将大鼠随机分为假手术组(生理盐水,10mL/kg)、模型对照组(生理盐水,10 mL/kg)、阳性对照组(尼莫地平,30 mg/kg)、七十味珍珠丸不同剂量组(0.52、1.04、2.08、4.17、8.33、16.67、33.34、66.68、133.36、266.72、533.44 mg/kg),每组18只,各组大鼠灌胃相应药物1次;灌胃25 min后,除假手术组外,其余各组大鼠均用线栓法制造脑缺血再灌注损伤模型。脑缺血24、48、72 h后,对各组大鼠进行神经行为学评级,检测大鼠脑梗死率以评价脑缺血各时段七十味珍珠丸的最佳有效时间点、最佳给药剂量(D_(max))和最大效应(最小脑梗死率,E_(max)),然后采用Thermo Kinetica 5.1软件对七十味珍珠丸给药剂量与脑梗死率进行量-时-效关系拟合,计算量效曲线下面积(AUClast)、滞留剂量(MRTlast);并检测各组大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)的水平。结果:与假手术组比较,模型组大鼠神经行为显著异常(P<0.05或P<0.01),脑梗死率明显增加(P<0.01),大鼠血清中SOD水平显著降低(P<0.01,48 h),MDA水平显著升高(P<0.05,48 h)。与模型对照组比较,尼莫地平组神经行为异常无显著变化(P>0.05),脑梗死率显著降低(P<0.01,24、48 h),大鼠血清中SOD水平显著升高(P<0.01,48 h),MDA水平显著降低(P<0.05,48 h);七十味珍珠丸2.08～33.34 mg/kg剂量组神经行为异常显著改善(P<0.05,24 h);脑缺血24 h,七十味珍珠丸4.17～133.36 mg/kg剂量组脑梗死率均显著降低(以33.34 mg/kg剂量组最低,P<0.05或P<0.01),33.34～533.44 mg/kg剂量组大鼠血清中SOD水平均显著升高(P<0.05),0.52～2.08、8.33、33.34、266.72、533.44 mg/kg剂量组MDA水平均显著降低(P<0.05),D_(max)为33.34 mg/kg、E_(max)为3.02%、AUClast为5 141.76 mg/kg、MRTlast为329.161 mg/kg;脑缺血48 h,七十味珍珠丸2.08～133.36 mg/kg剂量组脑梗死率均显著降低(以66.68 mg/kg剂量组最低,P<0.05或P<0.01),1.04～533.44(除4.17外)mg/kg剂量组大鼠血清中SOD水平均显著升高(P<0.05),16.67～66.68、533.44 mg/kg剂量组大鼠血清中MDA水平均显著降低(P<0.05),D_(max)为66.68 mg/kg、E_(max)为2.13%、AUClast为5 219.36 mg/kg、MRTlast为340.521 mg/kg;脑缺血72 h,七十味珍珠丸各剂量组脑梗死率、MDA水平均无显著降低(P>0.05),SOD水平均无显著升高(除0.52 mg/kg剂量组外,P>0.05)。结论:七十味珍珠丸治疗大鼠脑缺血再灌注损伤的最佳有效时间点为48 h、D_(max)为66.68 mg/kg,其改善机制可能与增强SOD水平、降低MDA水平有关。     

氰戊菊酯染毒大鼠肺灌洗液中细胞与生化效应

给大鼠一次气管注入氰戊菊酯悬液(FS)以及中毒室内吸入氰戊菊酯(FA),通过分析BALF中细胞与生化组分评价肺脏的毒性反应。结果表明PAM_s数下降,PMN数、Alb和NANA含量增加,LDH、ALP和ACP活性升高,提示氰戊菊酯引起肺细胞生物膜损伤、弥漫性肺泡炎和肺水肿。氰戊菊酯的阈剂量和阈浓度分别为0.93 mg/kg和200 mg/m~3,阈下剂量和阈下浓度为0.19 mg/kg和40 mg/m~2。研究结果为探讨氰戊菊酯的肺脏毒性及其机理,为制订其卫生标准提供依据。     

冠心舒对鹌鹑实验性高胆固醇血症和小鼠凝血时间的影响

对照组与给药组的鹌鹑均用诱发饲料(其中含胆固醇1％和脂肪20％)喂饲。冠心舒200mg/kg/d ip,药后第4、6周血清胆固醇均比对照组降低31％(P<0.001)。提示冠心舒有显著的预防血清胆固醇升高的作用。另外冠心舒120mg/kg ip可使小鼠凝血时间延长,药后1h、2h分别比对照组延长10.26s(P<0.01)和1.02s(P<0.05),药后6h恢复正常。     

急性氰戊菊酯中毒大鼠肺泡细胞形态的动态变化

用扫描电镜观察氰戊菊酯(Fen)经气管染毒大鼠肺灌洗液(BALF)中肺泡细胞形态的动态变化,结果0.19 mg/kg染毒未诱发肺损伤,0.93 mg/kg仅引起轻度肺泡炎,4.7 mg/kg和(或)23.3 mg/kg导致肺实质损伤。肺泡巨噬细胞(PAM)表面呈现不同形状的凹窝、空洞及表面皱褶(或胞浆指状突起)的不规则样变,以至肺泡细胞大量裂解死亡。中性白细胞(PMN)、单核细胞(Mc)、淋巴细胞(Lc)、Ⅱ型肺泡上皮细胞(EPⅡ)、纤毛细胞(CC)及红细胞(RBC)显著增多,并出现多个细胞的聚集。上述反应发生于染毒后30 min,4～24 h达高峰,4 d后恢复正常。本研究为探讨Fen对肺的毒性、毒理和制订用药卫生标准提供了细胞形态学依据。     

新癀片对动物发热模型的解热作用研究

目的研究新癀片对不同动物模型的解热作用。方法制备酵母致大鼠发热、牛奶致家兔发热、内毒素致家兔发热模型测量给药后各组的体温,计算各组大鼠体温与基础体温差值以及各给药组降温率。结果新癀片95.0 mg/kg剂量组在药后1~4.5 h,47.5 mg/kg剂量组药后4、4.5 h对酵母所致大鼠体温升高有显著的抑制作用。药后1 h,新癀片47.5 mg/kg剂量组牛奶致发热家兔体温开始下降;药后2 h,47.5、23.8 mg/kg剂量组家兔体温均下降显著,一直持续到药后5 h,仍有显著的降温作用。新癀片47.5 mg/kg剂量能够显著降低内毒素致发热家兔各时间点体温的升高,在药后4、5 h时对体温的降温率达50.3%、85.2%。结论新癀片对酵母致大鼠发热、牛奶致家兔发热和内毒素致家兔发热均有很好的解热作用。     

葎草水提物止痒作用的实验研究

目的：研究葎草水提物的止痒作用。方法：通过采用4-氨基吡啶（4-AP）诱发小鼠皮肤瘙痒反应、氯喹诱发小鼠全身瘙痒反应、组胺致豚鼠局部瘙痒反应及2,4-二硝基氟苯（DNFB）致小鼠右耳廓迟发型变态反应的瘙痒动物模型,并用放射免疫分析方法（RIA）测定氯喹致小鼠瘙痒后血清中IL-4的含量,观察葎草水提物的止痒作用。结果：葎草水提物100、30mg/kg显著抑制4-AP和氯喹诱发小鼠瘙痒反应的持续时间,其中100mg/kg可显著减少搔痒次数,并显著降低氯喹诱发小鼠瘙痒反应后血清中IL-4的含量;葎草水提物25、7.5mg/kg显著提高豚鼠致痒阈;100、30mg/kg显著抑制DNFB致小鼠右耳廓肿胀。结论：葎草水提物具有止痒作用,可能与抑制组胺和IL-4的释放有关。     

云南产螺旋藻多糖抗氧化抗疲劳作用的实验研究

从云南产螺旋藻中分离纯化出螺旋藻多糖（PSP）。12～14 mo小鼠igPSP100mg/kg、200 mg/kg,能降低心、肝、脑组织MDA含量,增加 RBC及脑SOD活力,使全血及肝应GSH-Px活性及 GSH含量升高。3～4 mo小鼠 ig PSP 100mg/kg、200 mg/比可提高血清 LDH活力,降低运动后血乳酸水平,并能延长小鼠游泳时间。表明PSP具有较明显的抗氧化抗疲劳作用。     

埃他卡林对脂多糖、油酸、二甘醇等所致肾脏损伤的影响

目的观察埃他卡林对脂多糖、油酸和二甘醇等不同因素所致肾脏损伤的影响。方法采用大鼠股静脉注射2%醋酸铅致敏后注射脂多糖1μg（1ml/kg）,4h造成内毒素休克肾损伤模型,大鼠左肾动脉注射油酸0.15ml/kg,24h造成油酸所致肾损伤模型,分别在造模前3d及1h,以埃他卡林1,3,9mg/（kg.d）灌胃给药;小鼠腹腔注射二甘醇10g/kg后,立即以埃他卡林1,3,9mg/（kg.d）灌胃给药6d,第7天造模成功。3种模型建立后,观察血清肌酐、尿素氮水平和肾脏形态学变化,评价肾脏功能。结果（1）内毒素性休克大鼠血清肌酐和尿素氮水平显著升高,组织病理显示有肾小球微血栓、肾小管上皮肿胀和管腔内蛋白管型形成。埃他卡林9mg/kg组能明显降低血清尿素氮和肌酐水平,改善上述病理变化。（2）左肾动脉注射油酸大鼠血清肌酐和尿素氮水平显著升高,组织病理显示肾小球内皮细胞坏死,球囊腔减小,肾小管间质充血且管腔内有蛋白管型形成。埃他卡林对油酸所致大鼠肾脏损伤无显著性改善作用。（3）二甘醇肾损伤小鼠血清肌酐水平显著性升高,埃他卡林9mg/kg组血清肌酐水平恢复至正常。结论埃他卡林不适合于脂多糖、油酸所致肾脏损伤的防治,埃他卡林可否用于二甘醇所致肾损伤的治疗值得进一步研究。     

Vomitoxin-induced dysregulation of serum IgA, IgM and IgG reactive with gut bacterial and self antigens.

The effect of dietary vomitoxin exposure on immunoglobulins that react with naturally occurring gut bacterial and self antigens was assessed in the B6C3F1 mouse. Ingestion of 25 ppm vomitoxin for 4 and 8 wk resulted in significantly elevated total IgA but depressed total IgG and IgM in serum when compared with control mice fed semi-purified diet only. IgA specific for phosphorylcholine (PC) and inulin (haptens associated with intestinal bacteria) increased significantly in mice fed vomitoxin whereas IgM with the identical specificity decreased. When sera were assessed for autoantibodies recognizing DNA and bromelated mouse red blood cells (MRBC), vomitoxin-exposed mice exhibited elevated specific IgA as compared with controls. This occurred together with decreases in DNA-specific IgG and IgM, and decreases in MRBC-specific IgM. Additionally, vomitoxin exposure did not enhance the specific serum IgA response to orally administered trinitrophenylated sheep red blood cells (TNP-SRBC), but significantly depressed TNP-specific serum IgG. The results suggest that hyperelevation of total and specific serum IgA for oral and self antigens occurs during vomitoxin feeding and that may be coupled with down-regulation of total and specific IgM or IgG. These effects could be contributory to the capacity of vomitoxin to induce IgA immune complex glomerulonephritis.     

混合性结缔组织病患者血清免疫球蛋白含量和补体C3C4的相关性的研究

目的 探讨混合性结缔组织病患者血清免疫球蛋白含量和补体C3C4相关性的关系及其临床意义. 方法用免疫速率比浊法测定68例混合性结缔组织病患者血清免疫球蛋白和补体C3C4含量,并与70名健康体检者进行对比分析.结果 患者组免疫球蛋白I gA、I gG和补体C3C4的含量与对照组相比有明显差异,差异具有统计学意义(P<0.05).患者组补体C3C4的含量具有直线相关性,(P<0.05).结论 混合性结缔组织病患者血清免疫球蛋白I gA、I gG和补体C3C4的含量与病情有关,可用于病情判断和预后评价.     

接触苯、甲苯工人血清免疫球蛋白的变化及意义

目的探讨苯、甲苯作业工人血清免疫球蛋白的变化,寻求苯、甲苯危害的早期指标。方法抽取接触苯、甲苯工人(苯作业组)及某五交化公司工人(非苯作业组)静脉血2ml,EDTANa2抗凝,静置4～5h分离血清,采用单向琼脂扩散法检测苯作业工人及对照组血清IgG、IgA,IgM含量。结果苯作业工人血清免疫球蛋白IgA增高,但与对照组比较无显著差异(P>0.05);IgG、IgM显著增高,与对照组比较差异有统计学意义(P<0.05)。结论IgG、IgM显著增高说明本组苯作业工人体液免疫反应较高,机体处于保护性免疫反应亢进状态,苯作业工人应及时采取保护措施。     

Alterations in immune parameters in foundry and pottery workers

To assess the immune competence of workers occupationally exposed to mainly silica, peripheral blood lymphocytes, serum immunoglobulins (IgG, IgA and IgM), C3 and C4 complement protein concentrations of foundry and pottery workers were evaluated and compared to healthy controls with no history of silica and other chemical exposure. The absolute number and percentage of functionally different subsets of peripheral blood mononuclear lymphocytes, i.e. T, T-suppressor and natural killer cells were unchanged. However, T-helper lymphocytes in pottery (P<0.05) and B cells in foundry (P<0.01) workers were significantly lower when compared to their controls. In addition, silica-exposed foundry workers had a significant reduction in the IgG, IgA and IgM levels. No significant differences were observed in the serum complement C3 and C4 levels of the workers. These results suggest that human chronic exposure to mainly silica and other chemicals originating from foundry and pottery settings may be detrimental to the immune system.     

Nuss与Ravitch两种术式对漏斗胸患儿免疫功能影响的对比研究

目的通过检测经Nuss手术及Ravitch手术治疗的先天性漏斗胸患儿手术前后的免疫指标，对比研究两种手术方式对漏斗胸患儿术后早期免疫功能的影响。方法回顾性分析80例漏斗胸手术，其中行Nuss手术40例（Nuss组），Ravitch手术40例（Ravitch组），2组分别于术前及术后第7天检测血清免疫球蛋白IgG、IgA、IgM含量。结果术前比较2组患儿的血清IgG、IgA、IgM含量无明显差异（P〉0．05），术后第7天检测显示Nuss组患儿血清IgG、IgA、IgM含量较Ravitch组患儿明显升高，差异有统计学意义（P〈0．05）；Nuss组中，术后7d血清IgG、IgA、IgM与术前相比均有明显升高（P〈0．05），而Ravitch组中仅IgA含量在术后7d与术前比较有明显差异（P〈0．05），IgG和IgM术后7d与术前比较，差异均无统计学意义（P〉0．05）。结论Nuss手术较Ravitch手术创伤性小，患儿术后机体免疫力恢复较早，更有利于患儿康复；免疫指标的检测可以作为评估漏斗胸患儿术后手术疗效及预后的辅助手段之一。     

生长抑素对恶性肠梗阻患者免疫功能的影响

目的:探讨应用生长抑素(商品名思他宁)非手术治疗恶性肠梗阻患者免疫功能的变化及临床意义。方法:将70例非手术治疗的恶性肠梗阻患者分为研究组和观察组,每组35例。研究组给予思他宁治疗;观察组给予常规治疗。检测治疗后两组患者的细胞免疫指标(CD 4+,CD 8+及CD 4+/CD 8+)、体液免疫指标(IgMI,gA和IgG)以及血清免疫调节因子(IL-1I,L-6和TNF-α)的变化,并观察两组患者并发症发生率的变化。结果:两组患者治疗后10 d的检测结果显示,研究组CD4+及CD4+/CD8+值明显高于观察组(P<0.05);IgMI,gA和IgG值明显高于观察组(P<0.05);血清IL-1I,L-6和TNF-α的浓度明显低于观察组(P<0.05)。研究组并发症发生率明显低于观察组(P<0.05)。结论:恶性肠梗阻患者应用生长抑素治疗能明显改善临床症状,提高保守治疗的成功率,同时能明显改善机体免疫功能,降低并发症发生率,有利于患者的康复。     

Quantitative Assessment of Mesangial Immunoglobulin A (IgA) Accumulation, Elevated Circulating IgA Immune Complexes, and Hematuria during Vomitoxin-lnduced IgA Nephropathy

Quantitative Assessment of Mesangial Immunoglobulin A (IgA)Accumulation, Elevated Circulating IgA Immune Complexes, andHematuria during Vomitoxin-lnduced IgA Nephropathy. Dong, W.,Sell, J. E., and Pectka, J. J. (1991). Fundam. Appl. Toxicol.17,197-207. Extended dietary exposure to the trichothecene vomitoxin(deoxynivalenol), a naturally occurring fungal contaminant ofcereal grains, induces elevated serum IgA and mesangial IgAaccumulation in a manner similar to the human glomerulonephritis,IgA nephropathy. A 12-week feeding study was conducted in theB6C3F1 mouse to evaluate the effects of exposure to 25 ppm dietaryvomitoxin over time on formation of IgA immune complexes (IgA-IQ,hematuria, and mesangial deposition of IgA, IgG, IgM, and complementcomponent C3. Both serum IgA and IgA-IC were significantly elevatedin vomitoxin-exposed treatment groups compared to controls atweeks 4, 8, and 12, whereas serum IgG was unaffected. The incidenceof hematuria was also significant in vomitoxin-exposed miceat weeks 4, 8, and 12. Quantitative immunofluorescence intensitymeasurements using interactive laser cytometer image analysisrevealed significantly greater mesangial IgA accumulation invomitoxin-fed mice compared to controls at weeks 4,8, and 12.Although glomerular IgG and IgM deposition was present in bothcontrols and treated mice, it was significantly lower in treatedmice as compared to controls at week 12. Mesangial C3 depositionwas not induced by vomitoxin feeding. Elevated IgA-IC, hematuria,and IgA mesangial accumulation occurring during exposure tovomitoxin mimicked human IgA nephropathy, whereas the absenceof mesangial C3 represented a major difference between thistoxin-induced immune deregulation and the human disease.     

经鼻饲肠内营养及护理在慢性阻塞性肺病机械通气患者中的应用

目的探讨慢性阻塞性肺病(COPD)机械通气患者经鼻饲肠内营养及护理的作用。方法38例患者分为2组,实验组给予鼻饲肠内营养4周,每周2次测定所有病人的IgA,IgG,IgM,转铁蛋白(TFN),前白蛋白(PAB),血清白蛋白(ACB)及一次脱机成功率。结果治疗2周末,实验组PAB、TFN及IgA、IgG、IgM均显著高于对照组(P<0.05)。治疗4周末,实验组所有指标均显著高于对照组(P<0.05)。结论经鼻饲肠内营养是COPD机械通气患者的重要治疗措施,良好细致的护理是保证其成功实施的关键。     

Acute lung injury from intratracheal exposure to fugitive residual oil fly ash and its constituent metals in normo- and spontaneously hypertensive rats

We have recently shown that the spontaneously hypertensive (SH) rats with underlying cardiovascular disease exhibited greater pulmonary vascular leakage and oxidative stress than healthy normotensive (Wistar Kyoto, WKY) rats after a 3-day inhalation exposure to residual oil fly ash (ROFA) particles (Kodavanti et al., 2000). Since host responsiveness to a 3-day episodic ROFA inhalation could be different from a single acute exposure, we examined ROFA and its constituent metal (vanadium, V; nickel, Ni)-induced lung injury after a single intratracheal (IT) exposure. Male SH and WKY rats (12-13 wk) were IT instilled with either saline or ROFA (0.0, 0.83 or 3.33 mg/kg). The bronchoalveolar lavage fluid (BALF) was analyzed for lung injury markers at 24 and 96 h post-IT. Rats were also IT instilled with 0.0 or 1.5 micromol/kg of either VSO(4) or NiSO(4).6H(2)O in saline (equivalent to a dose of 2-3 mg ROFA), and assessed at 6 and 24 h post-IT. Basal levels of BALF protein, macrophages, and neutrophils, but not lactate dehydrogenase (LDH), were higher in control SH compared to control WKY rats. Lung histology of control SH rats exhibited mild focal alveolitis and perivascular inflammation; these changes were minimal in control WKY rats. ROFA-induced increases in BALF protein, and to a lesser extent in LDH, were greater in SH compared to WKY rats. ROFA IT was associated with the increases in BALF total cells in both strains (SH > WKY). BALF neutrophils increased at 24 h and macrophages at 96 h in a dose-dependent manner (SH > WKY). The increase in BALF neutrophils was largely reversed by 96 h in both rat strains. The V-induced increases in BALF protein and LDH peaked at 6 h post-IT and returned to control by 24 h in WKY rats. In SH rats, BALF protein and LDH were not affected by V. Ni caused BALF protein to increase in both strains at 6 and 24 h; however, the control values at 24 h were high in SH rats, and were not distinguishable from exposed rats. The Ni-induced increase in LDH activity was progressive over a 24-h time period (WKY > SH). The number of macrophages decreased following V and Ni exposure at 6 h, and this decrease was reversed by 24 h in both strains. V caused BALF neutrophils to increase only in WKY rats. The Ni-induced increase in BALF neutrophils was more dramatic and progressive than that of V, but was similar in both strains. Lung histology similarly revealed more severe and persistent edema, perivascular and peribronchiolar inflammation, and hemorrhage in Ni- than in V-exposed rats. This effect of Ni appeared slightly more severe in SH than in WKY rats. In summary, the acute single IT exposure to ROFA resulted in greater pulmonary protein leakage and inflammation in SH rats than in WKY rats. The metallic constituents of ROFA produced these effects in a strain-specific manner such that, at the dose level used, V caused pulmonary injury only in WKY rats, whereas Ni was toxic to both strains.