高静
神经药理及新药研究
个性化签名
- 姓名:高静
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
中药学
- 研究兴趣:神经药理及新药研究
高静, 女,1966年10月28日生。1984年进入南京大学生物系生理专业学习, 1994年毕业, 获理学博士学位。同年留校,任教于医学院药理学教研室。1997年获“ 南京大学药理学教学改革与成果二等奖”。1998年7月-1999年7月赴美国伊利诺宜大学进修。现兼任南京大学医学院药物研究所所长。研究方向:神经药理及新药研究。已发表论文50余篇,申请专利三项。
主要研究成果:
1. 抗谷氨酸兴奋性神经毒性机制的研究。发现谷氨酸可透过胎盘屏障产生神经毒性,而吗啡、?-内啡肽、镧系元素、单纯疱疹病毒均可增强谷氨酸的神经毒性。银杏叶提取物(EGb761)则可逆转由谷氨酸、海人藻酸、?-淀粉样蛋白诱导的神经元退变。其机制与清除自由基、增强胞内钙平衡能力有关。
2. 脑内硫氧还蛋白(Trx)在抑制神经元损伤,尤其是线粒体缺陷神经元氧化应激损伤方面有重要作用,为神经退变病的防治开辟了新思路。
3. 榄仁叶提取物可对抗急、慢性化学性、免疫性肝损伤、抗炎,且对肿瘤细胞的生长有抑制作用,获得有效单体化合物两种,为乌苏酸和亚细亚酸,其抗肝损伤的机制与保护线粒体、清除自由基、抑制Il-6过度表达有关。
参加的学术团体
1. 国际脑研究组织(团体)
2. 中国神经科学学会
3. 中国心理学会生理心理专业委员会
4. 中国药理学会抗衰老专业委员会(理事)
5. 江苏省药理学会(理事)
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主页访问
2165
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成果阅读
725
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成果数
7
【期刊论文】Hepatoprotective activity of Terminalia catappa L. leaves and its two triterpenoids
高静, Jing Gao, Xinhui Tang, Huan Dou, Yimei Fan, Xiaoning Zhao, and Qiang Xu
Journal of Pharmacy and Pharmacology, 2004, 56: 1-7,-0001,():
-1年11月30日
The aim of this study was to evaluate the effect of the chloroform extract of Terminalia catappa L. leaves (TCCE) on carbon tetrachloride (CCl4)-induced acute liver damage and D-galactosamine (D-GalN)-induced hepatocyte injury. Moreover, the effects of ursolic acid and asiatic acid, two isolated components of TCCE, on mitochondria and free radicals were investigated to determine the mechanism underlying the action of TCCE on hepatotoxicity. In the acute hepatic damage test, remarkable rises in the activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (5.7-and 2.0-fold) induced by CCl4 were reversed and significant morphological changes were lessened with pre-treatment with 50 and 100mgkg 1 TCCE. In the hepatocyte injury experiment, the increases in ALT and AST levels (1.9-and 2.1-fold) in the medium of primary cultured hepatocytes induced by D-GalN were blocked by pre-treatment with 0.05, 0.1, 0.5gL 1 TCCE. In addition, Ca2+-induced mitochondrial swelling was dose-dependently inhibited by 50-500M ursolic acid and asiatic acid. Both ursolic acid and asiatic acid, at concentrations ranging from 50 to 500M, showed dose-dependent superoxide anion and hydroxyl radical scavenging activity. It can be concluded that TCCE has hepatoprotective activity and the mechanism is related to protection of liver mitochondria and the scavenging action on free radicals.
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高静, Xin-Hui Tang, *, †, Jing Gao, Feng Fang, Jin Chen, Li-Zhi Xu, Xiao-Ning Zhao*, and Qiang Xu*
The American Journal of Chinese Medicine, Vol. 33, No.4, 627-637,-0001,():
-1年11月30日
The protective effects of oleanolic acid (OA) on carbon tetrachloride (CCl4)-induced liver mitochondrial damage and the possible mechanisms were investigated. Pretreatment with OA prior to the administration of CCl4 significantly suppressed the increases of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (4.2-and 19.9-fold, respectively) in a dose-dependent manner in mice. The dissipation of mitochondrial membrane potential (14.8%) and intra-mitochondrial Ca2+ overload (2.1-fold) in livers of CCl4-insulted mice were also dose-dependently prevented by pretreatment with 20, 50 or 100mg/kg OA. In addition, the effects of OA on liver mitochondria permeability transition (MPT) induced by Ca2+ were assessed by measuring the change in mitochondrial membrane potential, release of matrix Ca2+ and mitochondrial swelling in vitro. The results showed that preincubation with 50 or 100μg/ml OA obviously inhibited the Ca2+-induced mitochondrial swelling, mitochondrial membrane depolarization and intra-mitochondrial Ca2+ release. It could be concluded that OA has protective effects on liver mitochondria and the mechanisms underlying its protection may be related to its inhibitory action on MPT.
Oleanolic Acid, Carbon Tetrachloride, Mitochondrial Permeability Transition, Mitochondrial Membrane Potential, Ca2+, , Mitochondrial Swelling.,
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【期刊论文】Inhibitory Effect of TCCE on CCl4-induced Overexpression of IL-6 in Acute Liver Injury
高静, Jing GAO*, Huan DOU, Xin-Hui TANG, Li-Zhi XU, Yi-Mei FAN, and Xiao-Ning ZHAO
Acta Biochimica et Biophysica Sinica 2004, 36(11): 1-6,-0001,():
-1年11月30日
Terminalia catappa L. leaves have been shown to protect against acute liver injury produced by some hepatotoxicants, but the active components and mechanisms are not clear. This study was designed to characterize the protective effects of the chloroform fraction of the ethanol extract of T. catappa leaves (TCCE) against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice, and analyze the changes in expression level of Interleukin-6 (IL-6) in the process. It was found that TCCE pretreatment (10 or 30mg/kg, ig) protected mice from CCl4 toxicity, as evidenced by the reversed alterations in serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST) activities. Additionally liver tissues were subjected to RT-PCR, Western blot and immunohistochemistry to analyze changes in IL-6 expression. It was found that TCCE markedly suppressed the CCl4-induced over-transcription of IL-6 gene. Consistent with the result, the expression of IL-6 protein was also blocked by TCCE in CCl4-stimulated mice, especially in the area around central vein on liver tissue section. In conclusion, TCCE is effective in protecting mice from the hepatotoxicity produced by CCl4, and the mechanisms underlying its protective effects may be related to the inhibition on the overexpression of IL-6 mainly around terminal hepatic vein.
acute liver injury, TCCE, CCl4, IL-6, expression
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高静, Xin-Hui Tang, *, Ling Gao, Jing Gao, Yi-Mei Fan, Li-Zhi Xu, Xiao-Ning Zhao*, and Qiang Xu†
The American Journal of Chinese Medicine, Vol. 32, No.4, 509-519,-0001,():
-1年11月30日
The hepatoprotective effects of the extract of Terminalia catappa L. leaves (TCE) against D-Galactosamine (D-GalN)-induced liver injury and the mechanisms underlying its protection were studied. In acute hepatic injury test, it was found that serum ALT activity was remarkably increased (3.35-fold) after injection of D-GalN in mice. But with oral pretreatment of TCE (20, 50 and 100mg/kg/d) for 7 days, change in serum ALT was notably reversed. In primary cultured hepatocytes from fetal mice, it was found that cell viability was decreased by 45.0% after addition of D-GalN, while incubation with TCE (0.1, 0.5 and 1.0mg/ml) for 36 hours could prevent the decrease in a dose-dependent manner. Meanwhile, D-GalN-induced both the increase of AST level (1.9-fold) and the decrease of SOD activity (48.0%) in supernatant of primary cultured hepatocytes could also be inhibited by pretreatment with TCE. In order to study the possible mechanisms underlying its hepatoprotective effects, one effective component separated from TCE, 2a, 3b, 23-trihydroxyursane-12-en-28-oic acid (DHUA), was used to determine anti-mitochondrial swelling activity and superoxide radicals scavenging activity in vitro. It was found that at the concentration range of 50-500 mmol/L DHUA, Ca2+-induced mitochondrial swelling was dose-dependently inhibited, and superoxide radicals scavenging activity was also shown in a dose-dependent manner. It was concluded that TCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the direct mitochondrion protection and strong scavenging activity on reactive oxygen species (ROS).
Terminalia catappa L., , 2a,, 3b,, 23-trihydroxyursane-12-en-28-oic acid (, DHUA), , Hepatoprotective Effects, D-Galactosamine, Mitochondria, Reactive Oxygen Species.,
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高静, Xinhui Tanga, c, Jing Gaoa, b, *, Jin Chena, Feng Fanga, Yanping Wanga, Huan Doua, Qiang Xub, Zhongming Qiand
Biochemical and Biophysical Research Communications 337(2005)320-324,-0001,():
-1年11月30日
The possible inhibition of ursolic acid (UA) on mitochondrial permeability transition (MPT) in mouse liver was investigated to identify the mechanisms underlying the hepatoprotective effect of UA. The effect of UA on liver MPT induced by Ca2+ was assessed by measuring changes in mitochondrial volume, mitochondrial membrane potential (MMP), release of matrix Ca2+, and transfer of cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) from the intermembrane space to the cytoplasm. The results showed that obvious mitochondrial swelling, loss of MMP, and release of matrix Ca2+ occurred after the addition of 50 lM Ca2+. However, preincubation with 20, 50 or 100 lg ml 1 UA significantly blocked the above changes. Addition of 100lg ml1 UA inhibited on mitochondrial swelling by 73.2% after 5min, while the MMP dissipating and Ca2+ releasing were, respectively, suppressed by 59.3% and 54.1% after 3min. In addition, Western blot analysis showed Cyt c and AIF transferred from mitochondrial pellet to the supernatant after the addition of 50lM Ca2+, but the process was significantly inhibited by various concentrations of UA. The results suggest that the mechanisms underlying the hepatoprotection of UA may be related to its direct inhibitory action on MPT.
Keywords: Ursolic acid, Mitochondrial permeability transition, Mitochondrial swelling, Mitochondrial membrane potential, Cytochrome c, Apoptosisinducing factor
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高静, Jing GAO*, Hui-Ying SUN, Zeng-Rong ZHU, Zhen DING, and Li ZHU
Acta Biochimica et Biophysica Sinica 2005, 37 (2): 119-125,-0001,():
-1年11月30日
Neuroprotective effects of dehydroepiandrosterone (DHEA) have been shown to be associated with its antioxidant properties, but the mechanisms remain unknown. Considering that the thioredoxin (Trx) system, an important cellular redox modulation system, changes under oxidative stress and could exert protective effects, the relationship between the antioxidant effects of DHEA and the Trx system regulation was explored. Using MTT assay and morphological observation, the effects of DHEA in the model of H2O2-induced oxidative stress in SH-SY5Y cells were analyzed, then RT-PCR and Western blot assay were used to detect the alteration in mRNA and protein level of Trx. The results showed that a pre-treatment of DHEA (10-100nM) protected cells against the toxicity induced by H2O2 in a dose-dependent manner, which could be confirmed in morphological observation by phase-contract microscope. In addition, Trx mRNA transcription was inhibited by H2O2 (300
dehydroepiandrosterone (, DHEA), , thioredoxin (, Trx), , H2O2, SH-SY5Y cell
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【期刊论文】Phytochemical and antiinflammatory studies on Terminalia catappa
高静, Y. M. Fan, L. Z. Xu, J. Gao*, , Y. Wang, X. H. Tang, X. N. Zhao, Z. X. Zhang
Fitoterapia 75(2004)253-260,-0001,():
-1年11月30日
The antiinflammatory activity of Terminalia catappa leaves ethanolic extract was studied using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in acute and chronic models. A bioassay-oriented fractionation procedure showed that the activity concentrates in the chloroform fraction. Ursolic acid (1) and 2a, 3b, 23-trihydroxyurs-12-en-28-oic acid (2), isolated from the chloroform fraction, exhibited strongantiinflammatory activities. The results suggest that the triterpenic acids 1 and 2 are responsible for the antiinflammatory activity of T. catappa leaves.
Terminalia catappa, 2a,, 3b,, 23-Trihydroxyurs-12-en-28-oic acid, Ursolic acid, Topical antiinflammatory activity, 12-O-Tetradecanoylphorbol-13-acetate
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