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Effects of total iridoid glycosides of Picrorhiza scrophulariiflora against non-alcoholic steatohepatitis rats induced by high-fat and high-sugar diet through regulation of lipid metabolism

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Chinese Herbal Medicines 2020年第1期12卷 67-72页

作者： Xu Xu Wei-ting Wang Zhuan-you Zhao Wen-gong Xi Bing Yu Chun-hua Hao Xin Li Wen-bin Hou Li-da Tang State Key Laboratory of Drug Delivery Technology and Pharmacokinetics Tianjin Institute of Pharmaceutical ResearchTianjin 300193China State Key Laboratory of Pharmacokinetics and pharmacodynamics Tianjin Institute of Pharmaceutical ResearchTianjin 300193China Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Institute of Radiation MedicinePeking Union Medical College&Chinese Academy of Medical SciencesTianjin 300192China

Objective:To investigate the therapeutic effect of total iridoid glycosides of Picrorhiza scrophulariiflora(TIGP)on non-alcoholic steatohepatitis(NASH).Methods:SD rats were fed with high-fat and high-sugar diet for 8 weeks to establish *** were given orally at doses of 20,40 and 80 mg/kg/d for 4 *** assay(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),fasting plasma glucose(FPG),fasting insulin(FINS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),chemokine-1(MCP-1),leptin(LEP)in serum were ***,TC,superoxide dismutase(SOD),malondialdehyde(MDA),and free fatty acid(FFA)in liver tissue were determined by colorimetric *** of hepatocytes and inflammation was performed by pathological ***:The results showed that TIGP significantly decreased TC,TG and FFA in liver tissue,increased SOD activity,decreased MDA content,decreased serum levels of TG,TC,HDL-C/LDL-C,ALT,AST,GLU,HOMA-IR,TNF-αand LEP,and in addition,improved steatosis of liver cells compared to ***:TIGP had anti-fatty liver effect against NASH rats induced by high-fat and high-sugar *** mechanism was related to the regulation of lipid metabolism and reduction of insulin resistance,through inhibition of oxidative stress and inflammation.

关键词： HOMA-IR leptin non-alcoholic steatohepatitis TNF-α total iridoid glycosides of Picrorhiza scrophulariiflora

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Effect of Tong-Qiao-Huo-Xue decoction on the expressions of related proteins of the blood-brain barrier and analysis of constituents in cerebrospinal fluid of cerebral ischemic rats

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中国药理学与毒理学杂志 2015年第S1期29卷 49-49页

作者： Ning WANG Li-li LI Qi-zhong JIN Ya-fang LIU Guang-yun WANG Yan WANG Key Laboratory of Xin′an Medicine Ministry of Education Anhui University of Chinese Medicine Hefei 230012 China Institute for pharmacodynamics and Safety Evaluation of Chinese Medicine Anhui Academy of Chinese Medicine Hefei 230012 China College of Pharmacy Anhui University of Chinese Medicine Hefei 230012 China

OBJECTIVE To evaluate the effects of Tong-Qiao-Huo-Xue decoction(TQHXD)on the bloodbrain barrier(BBB)permeability and the expressions of related proteins on the rats;and to analyse the constituents in the cerebrospinal fluid on the rats with cerebral ischemic *** Cerebral ischemia rats were induced by middle cerebral artery occlusion(MCAO).Adult male sprague-dawley(SD)rats were randomly divided into seven groups:sham-group;model group;nimodipine(NMP)-treated group and nao mai tai(NMT)-treated group were set as positive drug control groups;TQHXD-treated group(3,6 and 12g·kg-1body weight);The neurological function of rats was estimated by neurological defect scoring after the 1,7and 15 dafter *** structure of the brain in rats were observed by hematoxylin and eosin(H&E)*** features of hippocampus neurons and the opening of tight junction(TJ)of BBB in rats were observed by transmission electron microscope(TEM).Western blotting was performed to detect the expression of ZO-1,occludin,claudin-5,AQP-4 and MMP-9 in BBB after cerebral ischemia *** analysis experiments:adult male SD rats were randomly divided into four groups:Distilled water was administered intragastrically sham-operated rats;Distilled water was administered intragastrically model rats by MCAO;TQHXD was administered intragatrically to rats in sham-operated group;TQHXD was administered intragestrically to rats in model group by *** and HPLC was used to detect three compounds,namely,muscone,ligustilide and hydroxysafflor yellow A,in rats cerebrospinal fluid(CSF)after oral administration of ***,samples of cerebrospinal fluid of rats in each group were compared with single medicine so as to explicit the three compounds come from which *** TQHXD significantly reduced the neurological defect *** examination indicated that dense neuropil and largely surviving neurons had been seen in TQHXD-treated rats.T

关键词： Tong-Qiao-Huo-Xue-Decoction blood-brain barrier ti

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Combination of Shengmai San and Radix puerariae ameliorates depression-like symptoms in diabetic rats at the nexus of PI3K/BDNF/SYN protein expression

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Animal Models and Experimental Medicine 2023年第3期6卷 211-220页

作者： Ayaz Ahmed Guirong Zeng Mudassar Azhar Fengzhong Wang Jingru Wang Bei Fan Xinmin Liu Dejiang Jiang Qiong Wang Institute of Food Science and Technology Chinese Academy of Agricultural SciencesBeijingChina Hunan Key Laboratory of pharmacodynamics and Safety Evaluation of New Drugs&Hunan Provincial Research Center for Safety Evaluation of Drugs ChangshaChina Dr.Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan Institute of Drug Discovery Technology Ningbo UniversityNingboChina Research Center for Pharmacodynamic Material Basis and Mechanism of ActionCollege of PharmacyGuizhou University of Traditional Chinese MedicineGuiyangChina Sino-Portugal TCM International Cooperation Center The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhouChina

Background:Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as *** individuals are more vulnerable to experience depression compared to the normal ***,novel treatment approaches are required to reduce depressive symptoms among diabetic *** Chinese medicines(TCMs)such as Shengmai San(SMS)and Radix puerariae(R)are usually widely used to treat ailments such as neurological com-plications since ancient ***:In this study,SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic *** antidepressant po-tential of the prepared combination was evaluated behaviorally using open field test,novelty-induced hypophagia,and forced swim test in diabetic rats with biochemical and protein expression(PI3K,BDNF[brain-derived neurotrophic factor],and SYN[pr-esynaptic vesicle protein])***:Diabetic rats(streptozotocin,45 mg/kg)showed elevated fasting blood glu-cose(FBG)>12 mM with depressive symptoms throughout the *** with R-SMS(0.5,1.5,and 4.5 g/kg)significantly reverted depressive symptoms in diabetic rats as evinced by significantly(p<0.05)reduced immobility time with an increased tendency to eat food in a novel *** with R-SMS also significantly increased the protein expression of PI3K,BDNF,and SYN protein,which play a crucial role in ***:This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats;thus,this formulation might be studied further to develop as an antidepressant.

关键词： BDNF depression Shengmai San STZ induced diabetes traditional Chinese medicine

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Hypotensive Effects and Phytochemical Profile of Aqueous Extract and Fractions of Desmodium velutinun Leaves (Willd) D. C. (Fabaceae) in the Rat

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Journal of Biosciences and Medicines 2022年第8期10卷 100-109页

作者： Blondy Mboungou-Bouesse Arnaud Wilfrid Etou Ossibi Elva Ngolo Romaric De Garde Elion Itou Béril Fabrice Mavouba Dieu-Merci Bevel Gallo Mongo Gouollaly Tsiba Ange Antoine Abena Laboratory of Biochemistry and Pharmacology Faculty of Health Sciences Marien Ngouabi University Brazzaville Republic of Congo Department of Pharmacopeia and Traditional Medicine National Institute of Health Science & Research Delhi India Laboratory of Chemistry Organic Biomolecules and Pharmacodynamics Science City (Ex-ORSTOM) Brazzaville Republic of Congo Plant and Life Chemistry Unit Faculty of Sciences and Techniques Marien Ngouabi Univesity Brazzaville Republic of Congo

Desmodium velutinum (D. velutinum) is a plant of the family Fabaceae used in traditional Congolese medicine for the treatment of high blood pressure (HBP) or hypertension (HT). The present work evaluated the hypotensive activity and determined the phytochemical profile of the aqueous extract and fractions of Desmodium velutinun (Willd) D. C. (Fabaceae) in the rat. The hypotensive effect of the aqueous extract and different fractions (F1, F2, F3 and F4) was evaluated at the dose of 2.5 mg/kg in normotensive rats anesthetized with 15% urethane at 1.5 g/kg, i.p. (intraperitoneally). Our results showed that the F3 fraction after administration caused a significant decrease in blood pressure and heart rate which remained higher than that of the aqueous extract and fractions (F1, F2 and F4). The richness in polyphenolic and flavonoid compounds as well as the separating capacity of the eluent used within the F3 fraction clearly justifies the beneficial effects of the latter on blood pressure and heart rate compared with the extract and fractions (F1, F2 and F4). In a second part we carried out the qualitative (thin-layer chromatography) and quantitative (total polyphenols and flavonoids determination) analysis. The chemical compounds remained dominated by the polyphenolic and flavonoid groups, the content of total polyphenols and total flavonoids meets the following increasing order: (extract, F1, F2, F3 and F4). The results obtained could certify the use of Desmodium velutinun in traditional Congolese medicine.

关键词： Hypotensive Fraction Desmodium velutinun Phytochemistry

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Phytochemical Screening and Toxicity Assessment of Imperata cylindrica (L.) P. Beauv. (Poaceae) Raw Extracts with Brine Shrimp (Artemia salina) Lethality Assay

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Journal of Biosciences and Medicines 2022年第8期10卷 153-171页

作者： Anne Marie Léticia Konan Koffi Julien Golly Adou Koffi Mathieu Kra Amissa Augustin Adima Essis Esmel Claude Lohoues Biochemistry Department Medical Sciences Faculty Felix Houphouet-Boigny University Abidjan C&ocirc te d’Ivoire Laboratory of the Biology of Immunity Center Pasteur Institute Abidjan C&ocirc te d’Ivoire pharmacodynamics Biochemical Laboratory Felix Houphouet-Boigny University Abidjan C&ocirc te d’Ivoire Research Department Water Chemicals and Natural Substances INP-HB Yamoussoukro C&ocirc te d’Ivoire

Background: Herbal medicinal preparations are used as dietary supplements for disease prevention and as alternative/complementary medicine. The growing interest in herbal medicine raises the question of its safety and efficacy. Numerous recorded cases of intoxication and toxicological studies reveal that medicinal plants can be toxic, which hinders their safe use. Plant intoxications related to a variety of factors include plant organs and many extraction solvents. Little toxicological data on medicinal plants is available. The need to investigate is important for safe use. Imperata cylindrica, a poaceae, is one of the medicinal plants for which few toxicological data are available. Materials & Methods: To expand toxicological data, water, 70% ethanol, and 30% acetone extracts of the leaves and roots, obtained by maceration and reflux methods, were used for phytochemicals molecules qualitative detection and toxicity test by the brine shrimp lethality assay. Results: The qualitative analysis of the different extracts revealed the presence of alkaloids, polyphenolic compounds, saponins, and polyterpenoids. The toxicity endpoint was lethal concentration 50 (LC50). The leaves’ extracts LC50 was between 489.78 μg/mL and 1066.6 μg/mL. As for the root extracts, the LC50 was between 341.98 μg/mL and 1530 μg/mL. Discussion: The different compounds’ presence justifies the use of Imperata cylindrica as a medicinal plant. According to Clarkson classification the root extracts are moderately toxic (LC50: 168.47 μg/mL), and leaf extracts are weakly toxic (LC50: 527.25 μg/mL). The extrapolation made in relation to the Gosselin, Smith, and Hodge scale, allows us to characterize the Imperata cylindrica root and leaf extracts as non-toxic to humans by oral route. Conclusion: This result can be a base for more precise toxicological studies.

关键词： Imperata cylindrica Poaceae Phytochemical Analyses Cytotoxicity Artemia salina

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Novel opioid-neurotensin-based hybrid peptide with spinal long-lasting antinociceptive activity and a propensity to delay tolerance development

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1440-1452页

作者： Karolina Fra˛czek Mattia Ferraiolo Emmanuel Hermans Magdalena Bujalska-Zadrozny Kaja Kasarello Anna Erdei Kamila Kulik Agnieszka Kowalczyk Piotr Wojciechowski Dorota Sulejczak Piotr Sosnowski Sebastian Granica Sandor Benyhe Katarzyna Kaczynska Lukasz Nagraba Artur Stolarczyk Agnieszka Cudnoch-Jedrzejewska Patrycja Kleczkowska Department of pharmacodynamics Centre for Preclinical Research(CBP)Medical University of WarsawWarsaw 02-097Poland Laboratory of Neuropharmacology Institute of NeurosciencesUniversite´Catholique de LouvainBrussels B-1200Belgium Department of Experimental and Clinical Physiology Centre for Preclinical Research(CBP)Medical University of WarsawWarsaw 02-097Poland Institute of Biochemistry Biological Research CentreHungarian Academy of SciencesSzeged H-6701Hungary Doctoral School of Therotecical Medicine University of SzegedSzeged H-6720Hungary Department of Respiration Physiology Mossakowski Medical Research CentrePolish Academy of SciencesWarsaw 02-106Poland Department of Experimental Pharmacology Mossakowski Medical Research CenterPolish Academy of SciencesWarsaw 02-106Poland Department of Neuropeptides Mossakowski Medical Research CentrePolish Academy of SciencesWarsaw 02-106Poland Department of Pharmacognosy and Molecular Basis of Phytotherapy Faculty of PharmacyMedical University of WarsawWarsaw 02-097Poland Department of Orthopaedics and Rehabilitation Medical University of WarsawWarsaw 04-749Poland

The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tolerance development, was assessed in an acute pain model. The PK23 chimera at a dose of 10 nmol/rat produced a potent pain-relieving effect, especially after its intrathecal administration. Compared with intrathecal morphine, this novel compound was found to possess a favourable side effect profile characterized by a reduced scratch reflex, delayed development of analgesic tolerance or an absence of motor impairments when given in the same manner, though some animals died following barrel rotation as a result of its i.c.v. administration(in particular at doses higher than 10 nmol/rat). Nonetheless, these results suggest the potential use of hybrid compounds encompassing both opioid and neurotensin structural fragments in pain management. This highlights the enormous potential of synthetic neurotensin analogues as promising future analgesics.

关键词： opioid neurotensin doses

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Skin Organoid Research Progress and Potential Applications

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International Journal of Dermatology and Venereology 2022年第2期5卷 101-106页

作者： Hong-Yang Li Kun Ren Cheng Wang Wen-Bo Bu Pharmacal Research Laboratory Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsHospital for Skin Diseases(Institute of Dermatology)Chinese Academy of Medical Science and Peking Union Medical CollegeNanjingJiangsu 210042China Jiangsu Center for pharmacodynamics Research and Evaluation China Pharmaceutical UniversityNanjingJiangsu 210009China Department of Dermatology Zhongda Hospital Southeast UniversityNanjingJiangsu 210009China Department of Surgery Hospital for Skin Diseases(Institute of Dermatology)Chinese Academy of Medical Science and Peking Union Medical CollegeNanjingJiangsu 210042China.

Skin diseases were characterized by various types and high incidence,which seriously affect people’s *** present,skin pathogenesis research and the therapeutic drug development for skin diseases are limited by the lack of reasonable research models that recapitulate the development of skin *** are three-dimensionally cultured cell populations derived from skin stem cells,which exhibits the ability of multicell assembly and the similar histological characteristics with the living tissues and *** article reviews the establishment of normal skin organoids and skin tumor organoids,and summarizes the application of skin organoids in the evaluation of drug sensitivity,pathological mechanism research,and individualized *** addition,the advantages and limitations of organoids in skin disease research are also discussed,which provides a basis for revealing the pathogenesis of skin diseases and developing preventive and therapeutic drugs for skin diseases.

关键词： skin disease organoid three-dimensional culture personalized treatment drug screening

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Maintenance time of sedative effects after an intravenous infusion of diazepam: A guide for endoscopy using diazepam

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World Journal of Gastroenterology 2008年第33期14卷 5197-5203页

作者： Mitsushige Sugimoto Takahisa Furuta Akiko Nakamura Naohito Shirai Mutsuhiro Ikuma Shingen Misaka Shinya Uchida Hiroshi Watanabe Kyoichi Ohashi Takashi Ishizaki Akira Hishida First Department of Medicine Hamamatsu University School of Medicine1-20-1 Handayama Higashi-ku Hamamatsu 431-3192 Japan Center for Clinical Research Hamamatsu University School of Medicine1-20-1 Handayama Higashi-ku Hamamatsu 431-3192 Japan Department of Gastroenterology Enshu General Hospital1-1-1 Tyuou Naka-ku Hamamatsu 430-0929 Japan Department of Pharmacoki-netics and pharmacodynamics School of Pharmaceutics Sciences University of Shizuoka52-1 Yada Suruga-ku Shizuoka 422-8526 Japan Department of Clinical Pharmacology and Therapeutics Hamamatsu University School of Medicine1-20-1 Handayama Higashi-ku Hamamatsu 431-3192 Japan Department of Clinical Pharmacology and Therapeutics Oita University1-1 Idaigaoka Hazama Yufu 879-5593 Japan

AIM: To examine whether the sedative effects assessed by psychomotor tests would depend on the cytochrome P450 (CYP ) 2C19 genotypes after an infusion regimen of diazepam commonly used forgastrointestinal endoscopy in Japan. METHODS: Fifteen healthy Japanese volunteers consisting of three different CYP2C19 genotype groups underwent a critical ? icker fusion test, an eye movement analysis and a postural sway test as a test for physical sedative effects, and a visual analog scale (VAS) symptom assessment method as a test for mental sedative effects during the 336 h period after the intravenous infusion of diazepam (5 mg). RESULTS: The physical sedative effects assessed by the critical flicker test continued for 1 h (t values of 5 min, 30 min and 60 min later: 4.35, 5.00 and 3.19, respectively) and those by the moving radial area of a postural sway test continued for 3 h (t values of 5 h, 30 h, 60 min and 3 h later: -4.05, -3.42, -2.17 and -2.58, respectively), which changed significantly compared with the baseline level before infusion (P < 0.05). On the other hand, the mental sedative effects by the VAS method improved within 1 h. The CYP2C19 genotype-dependent differences in the postinfusion sedative effects were not observed in any of the four psychomotor function tests. CONCLUSION: With the psychomotor tests, the objective sedative effects of diazepam continued for 1 h to 3 h irrespective of CYP2C19 genotype status and the subjective sedative symptoms improved within 1 h. Up to 3 h of clinical care appears to be required after the infusion of diazepam, although patients feel subjectively improved.

关键词： Diazepam Sedation cytochrome P450(CYP) 2C19 Endoscopy Complication Critical flicker fusion test Eye movement analysis Postural sway test Visual analog scale

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Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2751-2777页

作者： Yurong Lai Xiaoyan Chu Li Di Wei Gao Yingying Guo Xingrong Liu Chuang Lu Jialin Mao Hong Shen Huaping Tang Cindy Q.Xia Lei Zhang Xinxin Ding Drug Metabolism Gilead Sciences Inc.Foster CityCA 94404USA Department of Pharmacokinetics Pharmacodynamics and Drug MetabolismMerck&Co.Inc.KenilworthNJ 07033USA Pharmacokinetics Dynamics and MetabolismPﬁzer Worldwide Research and DevelopmentGrotonCT 06340USA Eli Lilly and Company IndianapolisIN 46221USA Drug Metabolism and Pharmacokinetics BiogenCambridgeMA 02142USA Drug Metabolism and Pharmacokinetics Accent TherapeuticsInc.LexingtonMA 02421USA Department of Drug Metabolism and Pharmacokinetics GenentechA Member of the Roche GroupSouth San FranciscoCA 94080USA Drug Metabolism and Pharmacokinetics Department Bristol-Myers Squibb CompanyPrincetonNJ 08540USA Bioanalysis and Biomarkers Glaxo Smith KlineKing of the PrussiaPA 19406USA Department of Drug Metabolism and Pharmacokinetics Takeda Pharmaceuticals International Co.CambridgeMA 02139USA Ofﬁce of Research and Standards Ofﬁce of Generic DrugsCDERFDASilver SpringMD 20993USA Department of Pharmacology and Toxicology College of PharmacyUniversity of ArizonaTucsonAZ 85721USA Current afﬁliation:Translational Medicine EMD Serono Research&Development InstituteInc.BillericaMA 01821USA Current afﬁliation:Drug Metabolism Gilead Sciences Inc.Foster CityCA 94404USA

Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical *** nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological *** progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the *** importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly *** increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME *** this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

关键词： Drug discovery and development New drug application Biologics license application Pharmacokinetics ADME New modalities Model-informed drug development Micro-physiological systems

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HIV-1 Tat对多巴胺的传递和小胶质细胞反应性的调节存在脑区特异性

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神经损伤与功能重建 2018年第7期 379-379页

作者： Miller DR Shaerzadeh F Phan L Sharif N Gamble-George J McLaughlin JP Streit WJ Khoshbouei H 聂昊 Department of Neuroscience University of Florida College of Medicine and Mc Knight Brain Institute Department of pharmacodynamics University of Florida College of Pharmacy

转录蛋白的反式激活因子HIV-1 Tat与多巴胺神经元发生变性的神经性获得性免疫缺陷综合症相关。使用在多西环素(Dox)调节下表达GFAP驱动的Tat蛋白的小鼠模型,我们研究了在喙状延髓黑质致密部(SNc)中的小胶质细胞与神经元的交互作用。小... 详细信息

转录蛋白的反式激活因子HIV-1 Tat与多巴胺神经元发生变性的神经性获得性免疫缺陷综合症相关。使用在多西环素(Dox)调节下表达GFAP驱动的Tat蛋白的小鼠模型,我们研究了在喙状延髓黑质致密部(SNc)中的小胶质细胞与神经元的交互作用。小胶质细胞和酪氨酸羟化酶(TH)的免疫组化结果显示,SNc中小胶质细胞与多巴胺能神经元的比例小于腹侧被盖区(VTA),与此同时,野生型小鼠经过7 d Dox暴露后,这种差异得以维持。野生型小鼠使用Dox对其小胶质细胞密度没有影响。在神经元对HIV-1 Tat的潜在不利影响的敏感性的研究中,我们发现体内HIV-1 Tat暴露选择性地降低SNc中的TH免疫反应性,但不降低VTA中的TH免疫反应性,与此同时,SNc中TH m RNA的水平保持不变。体内HIV-1 Tat诱导不会改变这些脑区中神经元的总数。用全细胞膜片移液管将Tat(5 ng)打入多巴胺神经元降低了自发放电活动。Tat诱导也导致小胶质细胞数量下降,但不导致小胶质细胞活化。因此,多巴胺能表型的消失是由于TH免疫反应性的丧失而不是由于神经元死亡——因为神经元死亡会诱发小胶质细胞激活。我们得出结论,HIV-1 Tat造成低多巴胺能状态的副作用是通过降低TH的免疫反应性和激发多巴胺能神经元的活性而产生的。在体内Tat暴露后小胶质细胞的减少提示小胶质细胞功能的受损,且多巴胺神经元和小胶质细胞之间存在双向交互的改变。

关键词： HIV-1 Tat 多巴胺能神经元小胶质细胞小胶质细胞-神经元交互神经性获得免疫缺陷综合征

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