环孢霉素A肾毒性的发病机制及人参总皂甙的预防作用

环孢霉素Ａ（ＣｓＡ）肾毒性的作用机理至今不十分明确，而反应性氧代谢产物（ＲＯＭ）与许多肾脏疾病有关。将Ｗｉｓｔａｒ大鼠分别给ＣｓＡ三种剂量１２．５、２５、５０ｍｇ·ｋｇ－１／ｄ日灌胃７天，大鼠出现急性肾功能不全，血肌酥、血清及肾皮质匀浆丙二醛显著升高，而肾皮质匀浆超氧化物歧化酶活性及全血谷胱甘肽过氧化物酶活性下降。在人参总皂甙及去铁敏预防组中，上述指标与正常组无显著差异，提示ＲＯＭ产生的增加及肾脏抗氧化能力的下降参与了ＣｓＡ所致的急性肾毒性，而入参总皂甙、去铁敏具有预防作用。     

Effect of ginsenoside Rb1 on long-term potentiation in the dentate gyrus of anaesthetized rats

Ginsenosides are the major principles of Panax ginseng and have various pharmacological actions on the central nervous system. In this report, we investigated whether ginsenoside Rb1 (10, 100 nmol l^-1, icv) could increase the population spike (PS) amplitude in a dose-dependent manner, and accelerate the maintenance phase of long-term potentiation (LTP) induced by high frequency stimulation (HFS) in the dentate gyrus of anaesthetized rats. However, it had no effect on basic synaptic responses evoked by test stimulation. Comparatively, ginsenoside Rb1 (10, 100 nmol l^-1, icv) inhibited the induction phase of LTP induced by HFS in a dose-dependent manner. This may be one of the mechanisms of action of ginsenoside Rb1 on synaptic transmission. The details of the mechanism need further investigation.     

Ginsenoside RB<Subscript>1</Subscript> the anti-ulcer constituent from the head of<Emphasis Type="Italic">Panax ginseng</Emphasis>

We previously reported that the butanol (BuOH) fraction of the head of Panax ginseng exhibited gastroprotective activity in peptic and chronic ulcer models. In order to identify the active constituent, an activity-guided isolation of the BuOH faction was conducted with a HCl x ethanol-induced gastric lesion model. The BuOH fraction was passed through a silica-gel column using a chloroform-methanol gradient solvent system, and six fractions (frs. 1-6) were obtained. The active fr. 5 was further separated by silica-gel column, to yield 6 subfractions (subfrs. a-f). Subfr. d was composed of ginsenosides Re, Rc and Rb1. The most active constituent was ginsenoside Rb1 (GRb1), a protopanaxadiol glycoside, which was investigated for its anti-ulcer effect. Gastric injury induced by HCl x ethanol, indomethacin and pyloric ligation (Shay ulcer) was apparently reduced with oral GRb1 doses of 150 and 300 mg/kg. GRb1 at these dosage significantly increased the amount of mucus secretion in an ethanol-induced model. The anti-ulcer effects were consistent with the result of histological examination. These results suggest that the major active constituent in the head of Panax ginseng is GRb1, and that anti-ulcer effect is produced through an increase in mucus secretion.     

人参皂甙Rg3联合三氧化二砷对人肝癌细胞增殖性的影响

目的探讨人参皂甙Rg3联合三氧化二砷对肝癌裸鼠移植瘤模型的治疗作用,观察其对移植瘤肝癌细胞增殖性的影响。方法采用人肝癌细胞株Bel-7402细胞,种植于32只雄性裸鼠皮下,随机分成联合用药组、Rg3组(5mg/kg、10mg/kg、20mg/kg)、三氧化二砷组及对照组。实验自肿瘤接种第3天开始,人参皂甙Rg3(3个剂量),隔日灌胃,共20次;三氧化二砷40μg.kg-1.d-1,每日腹腔内注射,连续28d;对照组为生理盐水。停药1周后,脱颈处死,完整取出瘤块,检测肿瘤的重量,计算抑瘤率。采用免疫组织化学法检测增殖细胞核抗原(PCNA)在裸鼠肝癌移植瘤组织中的表达情况。结果三氧化二砷组抑瘤率(55.25%)高于Rg3组(5mg/kg亚组为32.24%、10mg/kg亚组为45.10%,20mg/kg亚组为50.00%),但随着Rg3浓度的升高,二者之间的差异明显减小;联合用药组中,5mg/kg亚组平均瘤重(0.58±0.15)g,抑瘤率61.84%;10mg/kg亚组平均瘤重(0.54±0.11)g,抑瘤率64.47%;20mg/kg亚组平均瘤重(0.49±0.12)g,抑瘤率67.76%,其抑瘤作用高于三氧化二砷组,差异有统计学意义(P<0.05)。三氧化二砷组抑制肝癌细胞增殖作用(PI值:38.3±5.3)强于Rg3组(PI值:5mg/kg亚组58.1±2.4;10mg/kg亚组51.8±5.3;20mg/kg亚组41.9±6.5),联合用药组(PI值:5mg/kg亚组38.6±8.4;10mg/kg亚组30.9±3.2;20mg/kg亚组23.3±3.3)作用最强(P<0.05),可以明显抑制移植瘤肝癌细胞增殖性。结论三氧化二砷对裸鼠肝癌移植瘤生长的抑制作用可能是通过抑制PCNA蛋白的表达。人参皂甙Rg3与三氧化二砷联合用药对移植瘤肝癌细胞增殖性的抑制有协同作用。     

吉林人参花蕾的化学研究(4)——人参皂甙Ro、Rb_1、Rf、Rg_1的分离与鉴定

继前文[1,2]报道从吉林人参(Panax ginseng C.A.Meyer)的花蕾中分离鉴定了七种人参皂甙(ginsenoside-Rb_2、-Rb_3、-Rc、-Rd、-Re、-Rg_2和20—glC—Rf)之后,又从中分离出五种人参皂甙(甙Ⅷ—Ⅻ)。通过测定其理化常数、IR、′H—NMR、~3C—NMR、EI—MS、FD—MS,制备衍生物,并与标准品对照鉴定了其中四种,甙Ⅷ、~1Ⅸ、Ⅸ、Ⅻ分别为ginsenoside-Ro、-Rb_1、-Rf和-Rg_1,另一种在鉴定中。ginsenoside-Ro(Ⅷ)和-Rf(Ⅻ)从人参花蕾中分离鉴定为首次报道。     

不同浓度人参皂甙Rd对次声性脑损害的保护

目的观察次声对大鼠记忆功能的影响及不同剂量人参皂甙Rd对其脑损害的治疗作用。方法通过Y型电迷宫训练将成绩相近的SD大鼠随机分为5个组，除正常对照组以外均接受16Hz 130dB的次声作用gh／d。3个药物组在次声作用前3d开始分别给予不同剂量（30mg／kg、10mg／kg、2mg／kg）的人参皂甙Rd。次声作用7d后再次评定每组大鼠的迷宫成绩，并用单链DNA（Single-stranded DNA，ssDNA）免疫标记法检测海马内ssDNA（凋亡细胞）数。结果与正常对照组相比单纯次声组大鼠学习记忆功能下降、标记的ssDNA阳细胞数明显增多（P〈0．05）；与单纯次声组相比人参皂甙（30mg/kg、10mg／kg组）有明显的保护作用，减轻了学习记忆功能下降，ssDNA阳性细胞数明显减少（P〈0．05）。结论16Hz 130dB次声可引发大鼠海马损伤、细胞凋亡、记忆功能减退，人参皂甙可明显减轻这些损害。     

Inhibitory Effects of Ginsenoside Rh2 on Tumor Growth in Nude Mice Bearing Human Ovarian Cancer Cells

Ginsenoside Rh₂ (Rh₂), isolated from an ethanol extract of the processed root of Panax ginseng CA Meyer, inhibits the growth of B16 melanoma cells. This study was designed to evaluate the ability of Rh₂ to inhibit growth of human ovarian cancer cells (HRA) in vitro and in nude mouse. Rh₂ inhibited proliferations of various established human ovarian cancer cell lines in a dose-dependent manner between 10 and 60 μM in vitro and induced apoptosis at around the IC₅₀ dose. When HRA cells were inoculated s.c. into the right flank of nude mice, all mice formed a palpable tumor within 14 days. Although i.p. administration of Rh₂ alone hardly inhibited the tumor growth, when Rh₂ was combined with cis-diamminedichloroplatinum(II) (CDDP) the tumor growth was significantly inhibited, compared to treatment with CDDP alone. When mice were treated p.o. with Rh₂ daily (but not weekly), the tumor growth was significantly (P<0.01) inhibited, compared to CDDP treatment alone. When Rh₂ was combined with CDDP, the degree of tumor growth retardation was not potentiated. The survival time was significantly (P<, we examined whether p.o. administration of Rh₂ has a dose-dependent inhibitory effect on the tumor growth. I.p. and weekly administration of CDDP had more potent antitumor activity in the order of 1 mg/kg, 2 mg/kg and 4 mg/kg, whereas p.o. and daily administration of Rh₂ (0.4 to 1.6 mg/kg) not only had antitumor activity comparable to that of 4 mg/kg CDDP, but also resulted in a significant increase of the survival. Doses of Rh₂ used in this study did not result in any adverse side-effects as confirmed by monitoring hematocrit values and body weight, unlike 4 mg/kg CDDP, which had severe side-effects. It is noteworthy that p.o. but not i.p. treatment with Rh₂ resulted in induction of apoptotic cells in the tumor in addition to augmentation of the natural killer activity in spleen cells from tumor-bearing nude mice. Thus, particularly in view of the toxicity of CDDP, Rh₂ alone would seem to warrant further evaluation for treatment of recurrent or refractory ovarian tumor.     

人参皂苷Rg1对大鼠视神经损伤病理改变的实验研究

目的研究人参皂苷Rg1对大鼠视神经损伤的影响。方法制作大鼠视神经损伤模型,设置实验组和对照组,腹腔注射人参皂苷Rg1,10mg／kg,连续注射20d,取视神经损伤眼和对照眼球及球后视神经,HE染色、SABC法免疫组织化学染色：Bcl-2、Neurocan表达情况。结果HE染色显示健康大鼠视神经组织细胞和视神经损伤组形态学有差异。免疫化学提示视神经损伤后神经细胞凋亡明显增多,人参皂苷Rg1腹腔注射能够明显改善细胞凋亡情况。视神经损伤后神经纤维蛋白表达明显增多,可能部分与其改善细胞凋亡情况有关,但机制尚不清楚。结论人参皂苷Rg1对大鼠视神经损有保护作用。     

人参总皂甙对脑出血后内源性神经干细胞增殖的影响

目的:探讨人参总皂甙对脑出血内源性神经干细胞(NSCs)增殖的影响。方法:SD大鼠随机分为人参总皂甙和单纯脑出血组各20只,3、7、14、28、60d各4只,应用立体定向技术,用大鼠自体尾动脉不抗凝血液75μl缓慢注入大鼠尾状核,制成中等量脑出血模型,两组术后饲养不同时间后观察神经干细胞增殖情况,术后第1d开始腹腔注射人参总皂甙,连续注射14d,分别在术后3、7、14、28、60d处死,运用免疫组织化学方法检测脑出血后各组损伤区周围神经干细胞的增殖情况。结果:两组在3、7d未发现NSCs增殖,14、28、60d组发现少量的NSCs增殖,人参总皂甙组14、28、60d均较单纯出血组神经干细胞明显增殖(P<0.01)。结论:脑出血后神经干细胞被激活增殖,人参总皂甙对脑出血后神经干细胞的增殖有促进作用和改善运动功能。     

大七厘散质量标准的研究

目的建立大七散的质量标准。方法采用高效液相色谱法对大七厘散中的主要成分人参皂苷Rg1进行定量分析,λ=203nm;同时对制剂中其他主要药材大黄、冰片、当归尾进行薄层鉴别。结果能准确对大黄、冰片、当归尾进行定性鉴别;人参皂苷Rg1在0．5710-4．2840ug范围呈良好线性关系。结论本方法快速、简便、准确、重现性好。