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Mitochondrial dysfunction and Huntington disease

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Neuroscience Bulletin 2006年第2期22卷 129-136页

作者： Wei-Yan ZHANG zhen-lun gu Zhong-Qin LIANG zheng-Hong QIN Soochow University School of Life Sciences Department of Pharmacology Soochow University School of Medicine Suzhou 215123 China

Huntington disease （HD） is a chronic autosomal-dominant neurodegenerative disease. The gene coding Huntingtin has been identified, but the pathogenic mechanisms of the disease are still not fully understood. This pa... 详细信息

关键词： mitochondrial dysfunction Huntington disease Huntingtin

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Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals

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World Journal of Gastroenterology 2006年第27期12卷 4359-4363页

作者： Fang Song Mei-Lin Xie Lu-Jia Zhu Ke-Ping Zhang Jie Xue zhen-lun gu Department of Pharmacology Medical School of Soochow University Suzhou 215123 Jiangsu Province China Suzhou Institute of Chinese Marteria Medica Suzhou 215123 Jiangsu Province China

AIM： To evaluate the effects of osthole on fatty liver, and investigate the possible mechanism. METHODS： A quail model with hyperlipidemic fatty liver and rat model with alcoholic fatty liver were set up by feeding high fat diet and alcohol, respectively. These experimental animals were then treated with osthole 5-20 mg/kg for 6 wk, respectively. Whereafter, the lipid in serum and hepatic tissue, and coefficient of hepatic weight were measured. RESULTS： After treatment with osthole the levels of serum total cholesterol （TC）, triglyceride （TG）, lower density lipoprotein-cholesterol （LDL-C）, coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased. The activity of superoxide dismutase （SOD） in liver was improved. In alcohol-induced fatty liver rats, the level of malondialdehyde （MDA） in liver was decreased. In high fat-induced fatty liver quails, glutathione peroxidase （GSH-PX） in liver was significantly improved. The histological evaluation of liver specimens demonstrated that the osthole dramatically decreased lipid accumulation. CONCLUSION： These results suggested that osthole had therapeutic effects on both alcohol and high fatinduced fatty liver. The mechanism might be associated with its antioxidation.

关键词： Hyperlipidemic fatty liver Alcoholic fatty liver Osthole Quails Rats

Therapeutic effect of osthole on hyperlipidemic fatty liver in rats

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Acta Pharmacologica Sinica 2007年第3期28卷 398-403页

作者： Yan ZHANG Mei-lin XIE~2 Lu-jia ZHU zhen-lun gu Department of Pharmacology,Medical School of Soochow University Suzhou 215123,China Department of Pharmacology Medical School of Soochow University Suzhou China

Aim:To study the effects of osthole on hyperlipidemic fatty liver and investigatethe possible ***:A rat model with hyperlipidemic fatty liverwas successfully established by feeding fatty milk for 6 *** experimentalrats were then treated with 5-20 mg/kg osthole for 6 *** mouse hyperlipi-demic model was induced by feeding fatty milk when they were treated with 10-20mg/kg osthole for 3 ***:After treatment with osthole,the levels of ratserum total cholesterol(TC),triglyceride(TG)and low density lipoprotein-choles-terol significantly decreased as compared with the fatty liver model group(P<0.05or P<0.01).Hepatic weight and its coefficient,the hepatic tissue contents of TC,TG,and malondialdehyde,also significantly decreased(P<0.05 or P<0.01).Infatty milk-induced hyperlipidemic mice,the post-heparin plasma activities of lipo-protein lipase(LPL),hepatic lipase(HL),and total lipase(TL)significantlyincreased after treatment with 10-20 mg/kg osthole for 3 weeks(P<0.05 or P<0.01).Importantly,the histological evaluation of rat liver demonstrated that ostholedramatically decreased lipid accumulation(P<0.01).Conclusion:Osthole wasfound to have therapeutic effects on fatty milk-induced rat fatty liver;the mecha-nisms might be associated with its anti-oxidation and the elevation of the activi-ties of LPL and HL.

关键词： osthole hyperlipidemic fatty liver pharmacology

Caspase-1 inhibitor Ac-YVAD-CHO attenuates quinolinic acid-induced increases in p53 and apoptosis in rat striatum

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Acta Pharmacologica Sinica 2005年第2期26卷 150-154页

作者： Yi CAO zhen-lun gu Fang LIN Rong HAN zheng-hong QIN Department of Pharmacology,Soochow University School of Medicine,Suzhou 215007,China Department of Pharmacology Soochow University School of Medicine Suzhou China

Aim:To study the effects of the caspase-1 inhibitor Ac-YVAD-CHO on quinolinicacid(QA)-induced ***:Rats were pre-treated with intrastriatalinfusion of Ac-YVAD-CHO(2-8μg)before intrastriatal injection of QA(60 nmol).Striatal total proteins,genomic DNA,and nuclear proteins were *** of Ac-YVAD-CHO on QA-induced caspase-1 activity,internucleosomalDNA fragmentation, IκB-α degradation,NF-κB,and AP-1 activation,and increasesin p53 protein levels were measured with enzyme assays,agarose gel electro-phoresis,electrophoresis mobility shift assays,and Western blot ***:Pre-treatment with Ac-YVAD-CHO inhibited QA-induced internucleo-somal DNA ***-YVAD-CHO inhibited QA-induced increases incaspase-1 activity and p53 protein levels,but had no effect on QA-induced IκB-αdegradation,NF-κB or AP-1 ***:Caspase-1 is involved inQA-induced p53 upregulation but not IκB-α *** of caspase-1attenuates QA-induced apoptosis in rat striatum.

关键词： caspase 1 Ac-YVAD-CHO Huntington disease protein p53 NF-kappaB inhibitor alpha apoptosis NF-kappaB

Puerarin reduces increased c-fos, c-jun, and type Ⅳ collagen expression caused by high glucose in glomerular mesangial cells

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Acta Pharmacologica Sinica 2005年第8期26卷 982-986页

作者： Cai-ping MAO, zhen-lun gu~1 Department of Pharmacology, Suzhou Institute of Chinese Materia Medica, Medical College of Soochow University Suzhou 215007, China Department of Pharmacology Suzhou Institute of Chinese Materia Medica Medical College of Soochow University Suzhou China

Aim: Increased expression of c-fos, c-jun and type Ⅳ collagen (CoⅣ) in glomerular mesangial cells (GMC) are important characteristics of diabetic nephropathy. Both c-los and c-jun regulate the gene expression of extracellular matrix components, and CoⅣ is the main component of the extracellular matrix. It has been reported that puerarin inhibits aggregation of the extracellular matrix in diabetic rats by an as yet unknown mechanism. The aim of this study is to investigate the effect of puerarin on c-fos, c-jun and CoⅣ expression in GMC cultured in medium containing 5.6 or 27.8 mmol/L glucose. Methods: The expressions of c-fos and c-jun were measured at the protein level using flow cytometry. CoⅣ content was detected using radioimmunoassay. Protein kinase C (PKC) activity was measured using liquid scintillation counting. Results: Puerarin (10-5mmol/L) significantly ameliorated the high-glucose effect on c-fos, c-jun and CoⅣ expression. This effect is accompanied by a reduced PKC activity in these cells. Coclusion: Our results suggest that reduced PKC activity and expression of c-fos and c-jun in GMC might participate in the mechanisms underlying the therapeutic effect of puerarin on diabetic nephropathy.

关键词： puerarin glomerular mesangial cells extracellular matrix diabetic nephropathy

Prostaglandin A1 inhibits increases in intracellular calcium concentration,TXA2 production and platelet activation

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Acta Pharmacologica Sinica 2006年第5期27卷 549-554页

作者： Yi ZHU zhen-lun gu Zhong-qin LIANG Hui-lin ZHANG zheng-hong QIN~2 Department of Pharmacology,Soochow University School of Medicine,Suzhou 215123,China Department of Pharmacology Soochow University School of Medicine Suzhou China

Aim:In our previous studies we found that cyclopentenane prostaglandin A1(PGA1) had neuroprotective effects in a rodent ischemic *** the presentstudy we aimed to investigate the inhibitory effect of PGA1 on platelet ***:The rate of aggregation of human platelets was measured by *** rate of adhesion of platelets to cultured endothelial cells wasdetermined by using [~3H]-adenine labeled platelets.5-Hydroxytryptamine releasefrom platelets was measured with O-phthaldialdehyde *** levels of TXB2,a stable metabolite of TXA2,were determined by *** in platelet morphology were observed using an electronmicroscope,and the intraplatelet free calcium concentrations were measured withFluo-3/AM FCM ***:PGA1 significantly inhibited thrombin-,col-lagen-and ADP-induced aggregation and adhesion of *** morphologi-cal changes of platelets induced by thrombin were blocked by ***1inhibited the release of 5-hydroxytyptamine from dense granules and the synthe-sis of ***:PGA1 inhibits the activation of platelets probablythrough blocking increases in intracellular calcium concentration and TXA2synthesis.

关键词： prostaglandin A1 platelet aggregation calcium TXA2

Molecular mechanism and regulation of autophagy

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Acta Pharmacologica Sinica 2005年第12期26卷 1421-1434页

作者： Ya-ping YANG~2 Zhong-qin LIANG~2 zhen-lun gu~2 zheng-hong QIN~(2,3) 2 Department of Pharmacology,Soochow University School of Medicine,Suzhou 215007,China Department of Pharmacology Soochow University School of Medicine Suzhou China

Autophagy is a major cellular pathway for the degradation of long-lived pro-teins and cytoplasmic organelles in eukaryotic cells.A large number of intracellu-lar/extracellular stimuli,including amino acid starvation and invasion ofmicroorganisms,are able to induce the autophagic response in *** discov-ery of the ATG genes in yeast has greatly advanced our understanding of themolecular mechanisms participating in autophagy and the genes involved in regu-lating the autophagic *** yeast genes have mammalian homologs,suggesting that the basic machinery for autophagy has been evolutionarily con-served along the eukaryotic *** regulation of autophagy is a very com-plex *** signaling pathways,including target of rapamycin(TOR)ormammalian target of rapamycin(mTOR),phosphatidylinositol 3-kinase-I(PI3K-I)/PKB,GTPases,calcium and protein synthesis all play important roles in *** molecular mechanisms and regulation of autophagy are dis-cussed in this review.

关键词： autophagy phosphatidylinositol 3-kinase Atg protein mTOR protein protein degradation

A short-chain α-neurotoxin from Naja naja atra produces potent cholinergic-dependent analgesia

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Neuroscience Bulletin 2006年第2期22卷 103-109页

作者： Hui-Ling ZHANG Rong HAN zhen-lun gu Zhi-Xing CHEN Bo-Wen CHEN Paul F. Reid Laurence N. Raymond zheng-Hong QIN Department of Pharmacology Soochow University School of Medicine Suzhou 215007 China ReceptoPharm Plantation Florida USA

Objective To investigate the analgesia induced by cobrotoxin （CT） from venom of Naja naja atra, and the effects of atropine and naloxone on the antinociceptive activity of CT in rodent pain models. Methods CT was administered intraperitoneally （33.3, 50, 75 μg/kg）, intra-cerebral venticularly （2.4 μg/kg） or microinjected into periaqueductal gray （PAG, 1.2 μg/kg）. The antinociceptive action was tested using the hot-plate test and the acetic acid writhing test in mice and rats. The involvement of cholinergic system and the opioid system in CT-induced analgesia was examined by pretreatment of animals with atropine （0.5 mg/kg, im or 10 mg/kg, ip） or naloxone （3 mg/kg, ip）. The effect of CT on motor activity was tested using the Animex test. Results CT （33.3, 50 and 75 μg/kg, ip） exhibited a dosedependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. In the mouse acetic acid writhing test, the intra-cerebral ventricle administration of CT 2.4 μg/kg （1/23th of a systemic dose） produced marked analgesic effects. Microinjection of CT 1.2 μg/kg （1/46th of systemic dose） into the PAG also elicited a robust analgesic action in the hot-plate test in rats. Atropine at 0.5 mg/kg （ira） or naloxone at 3 mg/kg （ip） failed to block the analgesic effects of CT, but atropine at 10 mg/kg （ip） did antagonize the analgesia mediated by CT in the mouse acetic acid writhing test. At the highest effective dose of antinociception （75 μg/kg）, CT did not change the spontaneous mobility of mice. Conclusion These results suggest that CT from Naja naja atra venom has analgesic effects. Central nervous system may be involved in CT＇ analgesic effects and the PAG may be the primary central site where CT exerts its effects. The central cholinergic system but not opioid system appears to be involved in the antinociceptive action of CT.

关键词： cobrotoxin analgesia periaqueductal gray matter atropine naloxone

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Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration Research 2025年第4期20卷 917-935页

作者： Dian Jiao Lai Xu zhen gu Hua Yan Dingding Shen Xiaosong gu Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated Hospital of Nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological *** regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of *** pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota *** results are lacking for conventional treatments for *** resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with ***-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research *** review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of *** also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current *** studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic ***,many new technologies for the diagnosis and treatment of epilepsy are being ***,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

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