藏药佐太的研究现状与进展

藏药佐太是一种古老的传统藏药,由水银、硫黄、八金、八矿等原辅料炮制而成。佐太含有汞、金、银、铅、铜、铁等多种金属,是藏药中重金属元素的主要来源,也是配制名贵藏成药的贵重原料,现代医药迫切需要对其临床合理应用进行深入研究。本文对近年来有关佐太的研究进行全面的分析和总结,从制备工艺、化学成分、药效学、药代动力学、毒理学、质量标准及临床应用等方面进行了综述。     

不同给药速度对舒芬太尼诱发的呛咳的影响

目的研究不同给药速度对舒芬太尼呛咳发生率及程度的影响,用以指导临床以合理的速度推注舒芬太尼。方法120例ASA评分Ⅰ-Ⅱ级的外科手术患者随机分为4组,分别以5s、10s、15S、20S的速度推注舒芬太尼0．4μg／kg,观察给药前（T1）、给药后1min（T2）时的平均动脉压、心率、Sp02、呛咳情况,呛咳依据咳嗽次数分为轻度（1—2次）、中度（3～5次）、重度（〉5次）。结果4组患者均发生了呛咳反应,呛咳发生率分别为33．3％、26．7％、23．3％、3．3％。58组,10S组和15s组呛咳发生率差异无统计学意义（P〉0．05）,20s组与其他3组呛咳发生率相比差异有统计学意义（P〈0．05）。20S组的咳嗽程度也比其他组明显减轻。发生呛咳前后对比,4组患者平均动脉压、心率、血氧饱和度均出现较小波动,但4组间差异无统计学意义（P〉0．05）。结论舒芬太尼外周静脉推注0．4μg／kg,推注时间〉20s时,呛咳反应的发生明显减少,是较为安全的推注速度。     

藏药佐太对大鼠CYP1A2和NAT2活性的影响

目的:研究藏药佐太对大鼠细胞色素氧化酶(CYP1A2)、药物代谢酶N-乙酰基转移酶2(NAT2)活性的影响。方法:将70只SD大鼠随机均分为正常对照(生理盐水)组和佐太低、中、高剂量(1.2、3.8、12 mg/kg)单次给药组和多次给药组(每天1次,连续12 d),分别ig给药。正常对照组、佐太单次给药组于第2天,佐太多次给药组于第13天分别ig给予咖啡因(25 mg/kg),5 h后采集尿液,按10 mg/ml加入维生素C。采用高效液相色谱法测定大鼠尿液中咖啡因代谢物5-乙酰氨基-6-甲酰氨基-3-甲基尿酸(AFMU)、1-甲基黄嘌呤(1X)、1-甲基尿酸(1U)、1,7-二甲基尿酸(17U)的含量,以(AFMU+1X+1U)/17U、AFMU/(AFMU+1X+1U)比值来反映CYP1A2和NAT2活性。结果:与正常对照组比较,佐太中剂量单次给药组及多次给药组、高剂量多次给药组大鼠(AFMU+1X+1U)/17U、AFMU/(AFMU+1X+1U)比值降低,即CYP1A2和NAT2活性降低,差异有统计学意义(P<0.05)。结论:佐太对大鼠CYP1A2和NAT2活性有明显抑制作用。     

比较舒芬太尼与芬太尼术后静脉给药的镇痛效果

目的比较舒芬太尼与芬太尼术后静脉给药的镇痛效果。方法选择2009年3月-2012年3月我院接诊的130例下腹部手术患者进行研究。按照随机数表法,均分为实验组和对照组。实验组采用舒芬太尼、对照组采用芬太尼术后静脉给药。采用VAS评分标准对两组患者术后疼痛状况进行评分。并对两组患者的麻醉后不良反应的发生情况进行分析。结果实验组患者在术后3h、6h、9h、12h、24h及48h的VAS评分明显低于对照组,两组比较有统计学意义（P〈0.001）。实验组患者嗜睡的发生率明显低于对照组,两组比较有统计学意义（P〈0.05）。实验组患者的恶心呕吐和眩晕的发生率与对照组无显著性差异（P〉0.05）。结论舒芬太尼的术后静脉给药的镇痛效果良好,明显优于芬太尼。     

藏药佐太的抗抑郁抗焦虑作用研究

目的 观察藏药佐太的抗抑郁和抗焦虑作用,并探讨其可能作用机制。方法 1）初步评价实验：在小鼠ig给予6.07、60.70、303.49、606.97 mg/kg佐太14 d后,通过强迫游泳实验和开场实验初步评价佐太对抑郁和焦虑的影响,同时通过检测小鼠血清中5-羟色胺（5-HT）和去甲肾上腺素（NE）水平来探讨佐太产生影响的可能作用机制。2）不可预测性慢性温和应激模型（CUMS）实验：建立CUMS模型,ig给予6.07、60.70、606.97 mg/kg佐太后,通过小鼠体质量变化、糖水偏爱实验、小鼠悬尾实验、开场实验和埋珠实验评价佐太对CUMS模型小鼠的抗抑郁和抗焦虑作用,同时检测小鼠血清中皮质酮（CORT）、促肾上腺皮质激素（ACTH）和下丘脑中促肾上腺皮质激素释放激素（CRH）水平,测定佐太对CUMS模型小鼠下丘脑-垂体-肾上腺（HPA）轴的影响。结果 1）佐太能够显著减少小鼠强迫游泳实验中不动时间（6.07、60.70、303.49、606.97 mg/kg）;增加小鼠在开场实验中中央区停留时间百分率（606.97 mg/kg）和中央区运动百分比（303.49、606.97 mg/kg）;增加小鼠血清中5-HT（6.07、606.97 mg/kg）和NE（6.07、303.49、606.97 mg/kg）水平。2）CUMS实验中,与对照组比较,经过42 d CUMS慢性应激小鼠表现出明显的抑郁和焦虑样行为,包括糖水偏爱率的降低、悬尾不动时间显著增加、开场实验中运动时间、中央区域停留时间及运动距离的减少和周边区域运动距离的增加、埋珠实验中埋珠个数的增加。而ig给予佐太（6.07、60.70、606.97 mg/kg）能够显著改善CUMS模型引起的上述症状,并且佐太（6.07、60.70 mg/kg）能够显著降低CORT、ACTH和CRH水平,抑制CUMS模型引起的HPA轴亢进。结论 佐太具有一定的抗抑郁和抗焦虑作用,并且其作用机制可能与升高5-HT、NE水平和抑制HPA轴亢进有关。     

藏药佐太对秦艽中龙胆苦苷药物动力学的影响

目的 探讨藏药佐太对秦艽中龙胆苦苷在家兔体内的药动学特征的影响.方法 对照组家兔给予龙胆苦苷提取液、实验组家兔给予龙胆苦苷和佐太的混合溶液后,采用RP-HPLC法测定给药后其血浆中的龙胆苦苷,DAS 2.0软件计算各组家兔血浆中龙胆苦苷的药动学参数.结果 对照组、实验组的家兔血浆中主要药物代谢动力学参数T1/2分别为1.66±0.32、1.74±0.39 h,AUC0-1分别为99.84±28.36、86.35±4.53 μg·h·ml-1,Cl分别为0.46±0.13、0.50±0.09 L·h-1,kg-1,Vd分别为1.10±0.39、1.24±0.25 L·kg-1,MRT分别为2.88±0.16、2.83±0.13 h.两组的主要药动学参数无显著性差异.结论 单次给予佐太对家兔龙胆苦苷的药动学特征无影响.     

硼替佐米不同给药途径对多发性骨髓瘤周围神经病变的影响

目的 通过比较静脉和皮下注射硼替佐米后多发性骨髓瘤(MM)患者周围神经病变(PN)发生的情况,探索减少硼替佐米治疗相关性PN更合适的给药途径.方法 选取2012年1月至2020年3月淮安市第一人民医院和上海健康医学院附属周浦医院收治的46例无PN的初诊MM患者.所有患者均使用含硼替佐米的方案治疗,22例采用静脉注射硼替...     

藏药四臣颗粒大鼠口服给药13周长期毒性研究

目的 通过13周长期毒性实验,观察四臣颗粒对大鼠的毒性反应,为临床安全用药提供依据。方法 SD大鼠128只,随机分为阴性对照组和四臣颗粒小、中、大剂量组,每组32只,雌雄各半。分别连续灌胃纯化水和四臣颗粒8.83,20.98和33.12g·kg^-1 13周。实验期间观察大鼠的一般状态,测定体质量和记录摄食量,分别于给药13周及停药4周后取部分大鼠进行眼科、血液学、凝血指标、血清生化学、电解质、尿液学、脏器系数及组织病理学检查。结果 给药期间四臣颗粒中、大剂量组体质量增长缓慢(P<0.05或P<0.01),雄性大剂量组摄食量增加(P<0.05或P<0.01),雌性中、大剂量组摄食量减少(P<0.05)。给药结束血液学检查显示,中、大剂量组RBC、HGB和HCT、MCHC降低(P<0.05或P<0.01),MCV、MCH、RDW升高(P<0.05或P<0.01),但数值在正常值范围内。给药组RETIC出现剂量-效应相关性升高(P<0.01)。雄性中、大剂量组尿胆红素显著升高(P<0.05)。给药组肝脏系...     

石榴皮多酚有效部位单次给药毒性及对无水乙醇致大鼠胃溃疡的保护作用

目的研究石榴皮多酚有效部位对小鼠单次给药毒性,评价其安全性,为新药研发和临床用药提供理论依据。观察石榴皮多酚有效部位对无水乙醇致大鼠胃溃疡的保护作用。方法选择健康昆明种小鼠50只,随机分为5组,每组10只,分别灌胃给予不同剂量的石榴皮多酚有效部位,连续观察14 d,每日记录各组小鼠一般情况、毒性反应及死亡情况,采用Bliss法计算半数致死量。选择健康大鼠70只,随机分为:正常组、模型组(等体积生理盐水)、三九胃泰颗粒组(1 850 mg·kg-1)、枸橼酸铋钾组(33 mg·kg-1)和石榴皮多酚有效部位低、中、高剂量组(430、852、1 704 mg·kg-1),连续灌胃10 d;d 10,除正常组外,其余各组采用无水乙醇灌胃(每只1.5 m L)致大鼠胃溃疡;计算各组胃溃疡指数、溃疡抑制率、观察胃黏膜组织形态学改变、测定胃黏膜组织中PGE2、NO、SOD、MDA含量。结果石榴皮多酚有效部位的半数致死量(LD50)为8 520.9 mg·kg-1,其95%的可信限范围为(7 291.2~9 914.4)mg·kg-1;病理学显示,给药剂量为16 000 mg·kg-1的小鼠脏器有不同程度的损伤。实验表明,与模型组比较,石榴皮多酚有效部位对胃黏膜损伤有明显修复作用,且明显升高胃溃疡大鼠胃黏膜NO含量、提高胃溃疡大鼠胃黏膜SOD活性及降低MDA含量、增加PGE2含量。结论石榴皮多酚有效部位给药剂量为5 063mg·kg-1未出现死亡,随着石榴皮多酚有效部位给药剂量的增加,给药剂量为16 000 mg·kg-1可造成小鼠的心、肝、肺、肾脏有不同程度的损伤,甚至导致死亡。石榴皮多酚有效部位的LD50为8 520.9 mg·kg-1,其95%的可信限范围为(7291.2~9 914.4)mg·kg-1。石榴皮多酚有效部位对无水乙醇致大鼠胃溃疡具有良好的保护作用,这种作用可能与促进胃溃疡上皮细胞合成、提高再生黏膜功能、增强抗氧化能力和诱导、促进NO合成有关。     

地佐辛不同给药方式对全麻术后苏醒与镇痛效果的比较

目的 比较地佐辛不同给药方式对瑞芬太尼复合麻醉术后苏醒期拔管与镇痛效果.方法 选择2015年4月~2016年4月我院收治的手术患者162例,随机分为观察组和对照组,每组患者81例.两组患者在手术中均采用瑞芬太尼复合麻醉的方法,手术结束前20min,两组患者均给予地佐辛,用量为0.2mg·kg-1.对照组患者采用静脉注射的方式给药,观察组患者采用肌肉注射的方式给药,对比两组患者术后苏醒时间和拔管时间,以及苏醒时、苏醒后1h、苏醒后2h的VAS疼痛评分.结果 观察组患者拔管时间和苏醒时间均低于对照组患者,苏醒后1h、苏醒后2h的VAS疼痛评分均低于对照组患者,差异均具有统计学意义(P<0.05).结论 采用肌肉注射的方法进行地佐辛给药,在瑞芬太尼复合麻醉术后苏醒期拔管与镇痛中,能够取得更为理想的临床效果.     

Lead selenide nanoparticles-induced oxidative damage of kidney in rats

ObjectiveTo investigate the effect of lead selenide nanoparticles (nano PbSe) on kidney in rats.MethodSpecific pathogen free SD rats were randomly divided into 4 groups (8 rats/group), and injected with of 0 mg/kg (control group), 10 mg/kg (low dose group), 20 mg/kg (middle dose group), or 30 mg/kg (high dose group) nano PbSe respectively. Seven weeks after injection, the serum was taken from rats for the detection of blood urea nitrogen (BUN), creatinine (Cr) and uric acid (UA). Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) levels were detected using renal tissue homogenate. Pathological examination was performed on kidney sections.ResultsThe levels of BUN and Cr in three exposure groups were significantly increased compared with those of control group. Levels of UA in middle dose and high dose group were higher than those in the control group. Levels of SOD, GSH-Px and T-AOC in three exposure groups were markedly decreased compared with those in the control group. Levels of MDA in three exposure groups were higher than those in the control group. Pathological changes at different levels of kidneys were observed, and the damage was more serious with the increase of concentration.ConclusionsNano PbSe can lead to oxidative damage to the kidney, with the toxicity positively correlates to the dosage.     

大鼠实验性高三酰甘油血症氧化损伤标志物研究

目的 建立大鼠高三酰甘油血症模型并观察模型鼠氧化损伤标志物及NADPH氧化酶的变化.方法60只雄性SD大鼠随机分为正常对照组、高三酰甘油血症模型组及阳性药物组,每组20只,模型组和阳性药物组采用高脂饲料喂养4周.测定基线及建模4周末的血清三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)及肝脏的TG、TC.以RT-PCR法检测建模6周末鼠肝NOX1-mRNA与NOX4-mRNA表达.阳性药物组4周末后以非诺贝特灌胃,剂量为100 mg·kg-1·d-1,持续2周后检测血清TG、HDL-C、LDL-C及TC.结果造模4周末,模型与阳性药物组血清TG、LDL-C、TC、肝脏TG、TC水平均较基线时明显升高(P<0.05);模型组与阳性药物组血清HDL-C明显低于其基线时水平(P<0.05).同时,模型组与阳性药物组血清MDA水平较基线时明显升高(P<0.05);SOD和GSH-PX较基线时明显降低(P<0.05).6周末模型组肝NOX1-mRNA与NOX4-mRNA表达均高于对照组与阳性药物组(P<0.05).阳性药物组经非诺贝特灌胃治疗2周后,血清TG、TC、LDL-C均明显下降(P<0.05),HDL-C明显上升(P<0.05).结论成功建立大鼠高三酰甘油血症模型,高三酰甘油血症大鼠GSH-PX和SOD明显降低,MDA明显上升,并通过激活体内NADPH氧化酶而诱导机体出现氧化损伤.     

Tetrahydrocurcumin: effect on chloroquine-mediated oxidative damage in rat kidney

Tetrahydrocurcumin is an antioxidative substance, which is derived from curcumin, the component of turmeric. In the present investigation, the effect of tetrahydrocurcumin and curcumin against chloroquine-induced nephrotoxicity were studied in female wistar rats. Oral administration of tetrahydrocurcumin significantly prevented the occurrence of chloroquine (970 mg/kg body weight)-induced renal damage. Upon administration of tetrahydrocurcumin to chloroquine-treated rats, the level of lipid peroxidation was significantly decreased while the levels of non-enzymic and enzymic antioxidants were significantly increased in kidney. Oral administration (80 mg/kg body weight) attenuated the chloroquine-induced nephrotoxicity by significantly decreased levels of serum urea and creatinine with significant normalization of creatinine clearance. On administration of tetrahydrocurcumin, the depleted renal antioxidant defense system (enzymatic and non-enzymatic antioxidants) was significantly increased in rats treated with chloroquine. These biochemical observations were supplemented by histopathological examination of kidney section. These results suggest that administration of chloroquine imposes an oxidative stress to renal tissue and that tetrahydrocurcumin protects the oxidative damage associated with chloroquine.     

Vitamin C coadministration augments bisphenol A,nonylphenol, and octylphenol induced oxidative damage on kidney of rats

The aim of this study was to investigate whether bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) induce oxidative stress on the kidney tissue of male rats and whether coadministration of vitamin C, an antioxidant, can prevent any possible oxidative stress. The Wistar male rats were divided into seven groups, including control, BPA, NP, OP, BPA+C, NP + C, OP +C. BPA, NP, and OP (25 mg/kg/day) was administered alone; vitamin C (60 mg/kg/day) was administered along with BPA, OP, and NP to the rats for 50 days. There was a decrease in serum concentration of blood urea nitrogen (BUN) in NP and OP groups compared with control group. Vitamin C coadministration with BPA, NP, and OP did not produce significant increase in BUN concentration in BPA +C, NP+ C, and OP + C group as compared with BPA, NP, and OP groups, respectively. The lowest serum creatinine activity and the highest lactate dehydrogenase (LDH) activity was present in kidney of BPA+C, NP+C and OP+C groups compared with BPA, NP, and OP groups. The malondialdehyde (MDA) levels were significantly higher while glutathione (GSH) levels were lower in treatment groups than controls. Furthermore, an increase was observed in MDA levels whereas a decrease was observed in GSH levels in BPA+ C, NP + C, and OP+ C groups compared with BPA, NP, and OP groups, respectively. These finding are in accordance with immunohistochemical staining of MDA and GSH. Histopathological examination of the kidneys of rats in BPA, OP, NP, BPA+ C, NP + C, and OP+ C groups revealed necrotic lesions, congestion, and mononuclear cell infiltration. In conclusion BPA, NP, and OP might induce oxidative damage in kidney of rats. In addition, coadministration of vitamin C with BPA, NP, and OP to male rats augments this damage in the kidney of male rats. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2011.     

益气补肾方药对顺铂致大鼠肾脏氧化损伤的保护作用

目的:探讨不同剂量中药对顺铂(DDP)所致大鼠肾脏氧化损伤的保护作用。方法:实验大鼠分为正常对照组、DDP模型组、低剂量中药组(10.8 g·kg^-1)、中剂量中药组(21.6 g·kg^-1)和高剂量中药组(32.4 g·kg^-1)。DDP模型组和3个中药组一次性尾静脉注射DDP (8 mg·kg^-1),正常对照组注射等量生理盐水。注射DDP当天起,3个中药组每日灌服相应剂量的中药煎剂。检测血清尿素氮(BUN)、肌酐(Cr)、肾皮质丙二醛(MDA)、一氧化氮(NO)含量和超氧化物歧化酶(SOD)、诱导型一氧化氮合酶(iNOS)的活性。结果:灌服中剂量中药组的大鼠与DDP模型组相比肾脏系数、BUN、Cr含量显著降低,肾皮质SOD活性显著升高,MDA、NO含量以及iNOS活性显著降低。结论:适当剂量的益气补肾方药可有效拮抗DDP所致的肾毒性,抑制DDP诱导的肾脏氧化损伤。     

Effect of thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat kidney

Objectives:

The biochemical effects of thiamine pyrophosphate on ischemia-reperfusion (IR) induced oxidative damage and DNA mutation in rat kidney tissue were investigated, and compared to thiamine.

Materials and Methods:

Rats were divided into four groups: Renal ischemia-reperfusion (RIR); thiamine pyrophosphate + RIR (TPRIR); thiamine + RIR (TRIR); and sham group (SG).

Results:

The results of biochemical experiments have shown that malondialdehyde (MDA) levels in rat kidney tissue after TRIR and TPRIR treatment were 7.2 ± 0.5 (P > 0.05) and 3.3 ± 0.3 (P < 0.0001) μmol/g protein, respectively. The MDA levels in the SG rat kidney tissue and in RIR group were 3.6 ± 0.2 (P < 0.0001) and 7.6 ± 0.6 μmol/g protein, respectively. Total glutathione (tGSH) levels in TRIR, TPRIR, SG, and RIR animal groups were 2.2 ± 0.3 (P > 0.05), 5.8 ± 0.4 (P < 0.0001), 6.2 ± 0.2 (P < 0.0001), and 1.7 ± 0.2 nmol/g protein, respectively. In the TRIR, TPRIR, SG, and RIR animal groups; 8-hydroxyguanine (8-OHGua)/Gua levels, which indicate mutagenic DNA, were 1.75 ± 0.12 (P > 0.05), 0.93 ± 0.1 (P < 0.0001), 0.85 ± 0.08 (P < 0.0001), and 1.93 ± 0.24 pmol/L, respectively.

Conclusions:

It has been shown that thiamine pyrophosphate prevents increase in mutagenic DNA in IR induced oxidative damage, whereas thiamine does not have this effect.KEY WORDS: DNA mutation, ischemia-reperfusion, oxidative damage, rat, thiamine pyrophosphate