人参皂甙Rb1对大鼠慢性缺氧性认知功能障碍的治疗作用

目的：目前尚无特效的防治慢性缺氧性认知功能障碍措施,前人的研究提示人参皂甙Rb1可能有上述功效,故本实验拟研究人参皂甙Rb1对大鼠慢性缺氧性认知功能障碍的治疗作用及其可能机制。方法：取雄性成年SD大鼠30只,随机分为对照组、模型组、人参皂甙Rb1（2 mg/kg·d）治疗组。采用Morris水迷宫行为学实验检测大鼠学习记忆功能,运用膜片钳技术在脑片水平检测海马的突出可塑性。结果：（1）模型组大鼠寻找平台潜伏期较对照组显著延长（P〈0.05）,在目标象限的停留时间较对照组明显缩短（P〈0.05）,人参皂甙Rb1治疗后,大鼠寻找平台潜伏期较模型组缩短（P〈0.05）,在目标象限的停留时间较模型组延长（P〈0.05）;（2）在高频强直刺激（HFS）作用下,各组均有长时程增强（LTP）现象,但模型组LTP较对照组明显减弱（P〈0.05）,人参皂甙Rb1治疗后LTP明显增强（P〈0.05）。结论：人参皂甙Rbl减轻了慢性缺氧大鼠在水迷宫实验中的行为学改变,并增强了慢性缺氧大鼠海马LTP,证实人参皂甙Rbl可明显减轻大鼠慢性缺氧性认知功能障碍,该作用与其减轻海马LTP抑制有关,为高原缺氧性认知功能障碍的防治提供了新思路,但其具体机制尚有待于进一步研究,本室将在此基础上进一步深入研究人参皂甙Rbl改善慢性缺氧性认知功能障碍的机制。     

人参皂甙Rb1对大鼠脑缺血再灌注神经损伤后的修复作用

通过阻塞大鼠大脑动脉,制备短暂性脑缺血大鼠模型,将出现神经功能缺失症状的大鼠随机分组,实施再灌注后立即按(40mg/kg)进行腹腔注射人参皂甙Rb1。结果发现大鼠脑缺血再灌注后,人参皂甙Rb1通过促进NAIP、Bcl-2表达和抑制Bax表达发挥神经损伤后的修复作用。人参皂甙Rb1给药组在各时间点的胶质细胞源性神经营养因子(GDNF)阳性细胞数远远高于单纯脑缺血再灌注组(P<0.01)。GDNF的表达与缺血性损伤有一定的联系,可认为人参皂甙Rbl对神经系统有一定保护作用。     

人参皂甙 Rb1与Re对大鼠缺血再灌注心肌细胞凋亡的影响

目的观察人参皂甙Rb1与Re对缺血再灌注心肌细胞凋亡的影响,并比较两者的效应差异.方法结扎Wistar大鼠左冠状动脉前降支,建立大鼠缺血再灌注动物模型;采用透射电镜、缺口末端标记法检测心肌凋亡细胞,利用光学显微镜进行细胞计数.结果 (1)透射电镜发现缺血再灌注组缺血区出现心肌凋亡细胞,假手术组未发现心肌凋亡细胞;(2)缺血再灌注组心肌细胞凋亡数为134.45±45.61个/视野,人参皂甙Rb1治疗组51.65±13.71个/视野,人参皂甙Re治疗组90.66±19.22个/视野,三组间有非常显著性差异(P<0.01).结论心肌缺血再灌注诱导心肌细胞凋亡,人参皂甙Rb1和Re均可显著减少缺血再灌注心肌细胞的凋亡.证实人参皂甙Rb1与Re均有抑制缺血再灌注心肌细胞凋亡,减轻心肌缺血再灌注损伤的作用;人参皂甙Rb1的抗心肌细胞凋亡作用较Re的效果为佳.     

人参皂甙 Rb1对大鼠缺血再灌注心肌细胞Bcl-2、Bax、Bad、Fas基因表达的影响

目的观察人参皂甙Rb1对缺血再灌注心肌细胞Bcl-2、Bax、Bad、Fas基因表达的影响.方法结扎/松解Wistar大鼠左冠状动脉前降支,建立大鼠缺血再灌注动物模型,免疫组化法检测Bcl-2、Bax、Bad、Fas基因的蛋白表达,并利用图象分析系统测量蛋白阳性表达区域平均光密度值,进行定量分析.结果缺血再灌注组及Rb1治疗组Bcl-2、Bax、Bad、Fas基因的表达较假手术组明显增加(P<0.05), Rb1治疗组Bcl-2的表达与缺血再灌注组比较无明显差异(P>0.05),而Bax、Bad、Fas的表达明显下降(P<0.05),人参皂甙Rb1治疗组Bcl-2/Bax、Bcl-2/Bad以及Bcl-2/Fas比值均较假手术组与缺血再灌注组明显增加.结论人参皂甙Rb1治疗可以抑制缺血再灌注心肌细胞中促凋亡基因Bax、Bad、Fas的表达,并使Bcl-2/Bax、Bcl-2/Bad以及Bcl-2/Fas比值增加.     

人参皂甙Rb1对阿尔茨海默病大鼠海马结构β-淀粉样蛋白表达的影响

目的观察人参皂甙Rb1对阿尔茨海默病（AD）模型大鼠学习记忆能力及海马结构β-淀粉样蛋白表达的影响。方法动物分3组：对照组、模型组及治疗组,用D半乳糖联合三氯化铝建立AD大鼠模型,治疗组在造模后给予人参皂甙Rb1腹腔注射4周;采用Morris水迷宫测试大鼠的空间学习记忆能力,用免疫组织化学方法观察海马结构β-淀粉样蛋白的表达。结果与对照组相比,模型组大鼠各时间段的逃避潜伏期均显著延长（P〈0．01）,海马CA1、CA3区及齿状回β-淀粉样蛋白表达的阳性细胞数明显增多（P〈0．01）;治疗组大鼠的逃避潜伏期较模型组明显缩短（P〈0．01）,海马CA1、CA3区及齿状回的β-淀粉样蛋白阳性细胞数显著减少（P〈0．01）。结论人参皂甙Rb1对AD模型大鼠学习记忆损害具有明显改善作用,其机制可能与人参皂甙Rb1减少海马结构β-淀粉样蛋白的表达有关。     

人参皂甙Rg1对脑缺血再灌注大鼠脑组织Bax和Bcl-2蛋白表达的影响

目的探讨人参皂甙Rg1对脑缺血再灌注大鼠脑组织Bcl-2和Bax表达的影响及其意义。方法分别给大鼠腹腔注射人参皂甙Rg1 10、20、40 mg/kg,采用大脑中动脉闭塞方法建立脑缺血再灌注模型,观察大鼠脑缺血再灌注后不同时间段（2 h、24 h）神经功能缺损评分;应用免疫组化法检测脑组织缺血再灌注24h后Bcl-2、Bax的表达。结果人参皂甙Rg1组大鼠脑缺血后各时间点神经功能缺损评分显著低于单纯缺血再灌注组（P〈0.05）;与单纯缺血再灌注组相比,人参皂甙Rg1各组Bcl-2表达显著增高,Bax表达显著降低,Bcl-2/Bax比值显著上调（P〈0.05）。结论人参皂甙Rg1防治大鼠脑缺血再灌注损伤的机制可能与促进脑组织Bcl-2表达、抑制Bax表达有关,且以高剂量效果较好。     

Ginsenoside Re impacts on biotransformation products of ginsenoside Rb1 by Cellulosimicrobium cellulans sp. 21 and its mechanisms

Ginsenoside Rg3, a known anti-cancer agent, is usually prepared by enzyme-mediated and acid hydrolysis of ginsenoside Rb1 and Rd. In this study, we used the bacterium Cellulosimicrobium cellulans sp. 21 to transform Rb1 into Rg3. When Rb1 was used as the sole substrate, the transformation products included Rg3, Rh2, C-K and PPD. However, when Rb1 and Re were mixed, the yield of Rg3 was significantly higher, indicating that Re attenuates the activity of β-1,2-glucosidase secreted by C. cellulans sp. 21. β-1,2-glucosidase hydrolyzes the β-1,2-glucose moiety at the C-3 position of Rb1, but Re dose not modify enzymes that produce Rg3 by hydrolyzing glucose at the C-20 position in aglycon. We also tested the inhibitory effects from various ginsenosides on β-1,2-glucosidase, and discovered that sugar chains played key roles in inhibiting β-1,2 glucosidase activity, whereas aglycones of protopanaxadiol and protopanaxatriol had little inhibitory effects. Some sugar chains with different linkages, such as C-20, C-3 and C-6, exhibited different inhibitory effects. Overall, our findings demonstrate that a combination of substrates, in addition to microorganism-secreted enzymes, can be used for selective biotransformation. This approach provides a novel strategy for natural product preparations via microbial transformation.     

Inhibitory effects of Ginsenoside Rb1 on apoptosis caused by HSV-1 in Human Glioma Cells

To investigate the inhibitory effects of Ginsenoside Rb1 (GRb1) on apoptosis caused by Herpes Simplex Virus-1 (HSV-1) in Human Glioma Cells (U251),U251 cells were infected by HSV-1 at a multiplicity of...     

Protective effect of vitamin B6 against doxorubicin-induced cardiotoxicity by modulating NHE1 expression

Doxorubicin (DOX) has been used to treat various types of cancer, but its application is limited due to its heart toxicity as well as other drawbacks. Chronic inhibition of Na⁺/H⁺ exchanger (NHE1) reduces heart failure and reduces the production of reactive oxygen species (ROS); vitamin B6 (VitB₆) has been demonstrated to have a crucial role in antioxidant mechanism. So, this study was designed to explore the effect of VitB₆ supplement on the DOX-induced cardiotoxicity and to imply whether NHE1 is involved. Ultrasonic cardiogram analysis revealed that VitB₆ supplement could alleviate DOX-induced cardiotoxicity; hematoxylin and eosin (HE) and Masson's staining further confirmed this effect. Furthermore, VitB₆ supplement exhibited significant antioxidative stress and antiapoptosis effect, which was evidenced by decreased serum malondialdehyde (MDA) content and increased serum superoxide dismutase (SOD) content, and decreased Bcl-2-associated X protein/B-cell lymphoma-2 ratio, respectively. Collectively, VitB₆ supplement may exert antioxidative and antiapoptosis effects to improve cardiac function by decreasing NHE1 expression and improve DOX-induced cardiotoxicity.     

Ginsenoside Rb1 enhances atherosclerotic plaque stability by skewing macrophages to the M2 phenotype

Atherosclerosis (AS) is characterized as progressive arterial plaque, which is easy to rupture under low stability. Macrophage polarization and inflammation response plays an important role in regulating plaque stability. Ginsenoside Rb1 (Rb1), one of the main active principles of Panax Ginseng, has been found powerful potential in alleviating inflammatory response. However, whether Rb1 could exert protective effects on AS plaque stability remains unclear. This study investigated the role of Rb1 on macrophage polarization and atherosclerotic plaque stability using primary peritoneal macrophages isolated from C57BL/6 mice and AS model in ApoE^?/? mice. In vitro, Rb1 treatment promoted the expression of arginase‐I (Arg‐I) and macrophage mannose receptor (CD206), two classic M2 macrophages markers, while the expression of iNOS (M1 macrophages) was decreased. Rb1 increased interleukin‐4 (IL‐4) and interleukin‐13 (IL‐13) secretion in supernatant and promoted STAT6 phosphorylation. IL‐4 and/or IL‐13 neutralizing antibodies and leflunomide, a STAT6 inhibitor attenuated the up‐regulation of M2 markers induced by Rb1. In vivo, the administration of Rb1 promoted atherosclerotic lesion stability, accompanied by increased M2 macrophage phenotype and reduced MMP‐9 staining. These data suggested that Rb1 enhanced atherosclerotic plaque stability through promoting anti‐inflammatory M2 macrophage polarization, which is achieved partly by increasing the production of IL‐4 and/or IL‐13 and STAT6 phosphorylation. Our study provides new evidence for possibility of Rb1 in prevention and treatment of atherosclerosis.     

卵巢早衰动物模型制备研究进展

卵巢早衰是一种典型异质性疾病,病因复杂多样。近年来,卵巢早衰的发病率有明显上升趋势,严重影响妇女身心健康和生活质量。建立一种理想可靠的卵巢早衰动物模型对研究卵巢早衰有着重要的临床意义。本文就国内外学者建立的卵巢早衰动物模型作一综述,讨论比较各种方法的优缺点。