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Critical role of PI3K/AKT in the restoration of endothelial function by heme oxygenase-1 in diabetic db/db mioce

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Critical role of PI3K/AKT in the restoration of endothelial ...

Hemin restores the impaired endothelium-dependent vasodilatation in diabetic db/db mice and the possible mechanisms involved

中国药理学会第十一次全国学术会议

作者： WT WONG cw lau Institute of Vascular Medicine and School of Biomedical Sciences Chinese University of Hong Kong SARChina

OBJECTIVE Heme oxygenase-1(HO-1),an inducible isoform of heme oxygenase,can exert vaso-protective ***,such vascular benefit in diabetic vasculopathy remains largely *** present study aims at investigating the impact of HO-1 induction on endothelial function in diabetic db/db *** Diabetic db/db and non-diabetic db/m mice were treated intraperitoneally with hemin(a potent inducer of HO-1) or vehicle for two *** aortae were isolated and suspended in myograph for isometric force measurement;levels of marker proteins were determined by the Western blotting method;nitric oxide (NO) production in cultured human umbilical vein endothelial cells(HUVEC) was estimated using NO-sensitive DAF-DA fluorescence *** Two-week hemin administration augmented endothelium-dependent relaxations in response to acetylcholine in db/db mouse aortae which was antagonized by the co-treatment with the HO-1 inhibitor Sn(IV) mesoporphyrinⅨdichloride(SnMP) and largely inhibited by the PI3K inhibitor wortmannin and Akt inhibitorⅤ.Overnight treatment with hemin and bilirubin(a metabolic product of HO-1 activity) in organ culture improved endothelial function in db/db mouse aortae and SnMP inhibited the effect of hemin but not that of bilirubin while Akt inhibitorⅤinhibited the effect of both hemin and *** hemin treatment increased the phosphorylation level of eNOS and Akt in diabetic mouse ***,hemin and bilirubin restored the lost NO production and increased eNOS and Akt phosphorylation in HUVECs exposed to high glucose and this effect was inhibited by Akt inhibitorⅤand dominant -negative Akt transfection which suppresses Akt *** addition,hemin treatment also improved the acetylcholine-induced relaxation in renal arteries from diabetic *** The present study demonstrates that the PDK/Akt signaling pathway is likely to mediate the vascular benefit of HO-1 induction in restoring the impaired endothelial f

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中国病理生理杂志 2010年第A10期26卷 2055-2055页

作者： WONG WT WONG SL lau cw Institute of Vascular Medicine and School of Biomedical Sciences Chinese University of Hong Kong

关键词： impaired endothelium monoxide protective oxygenase exert potent hemin inducer benefit

ROS does not contribute to acute development of nitroglycerine tolerance in rat aortas

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ROS does not contribute to acute development of nitroglyceri...

Hemin restores the impaired endothelium -dependent vasodilatation in diabetic db/db mice and the possible mechanisms involved

中国病理生理学会第九届全国代表大会及学术会议

作者： DOING JH WONG SL TIAN XY LEE HK LEE WY lau cw Institute of Vascular Medicine and School of Biomedical Sciences Chinese University of Hong Kong

＜正＞The development of nitroglycerine tolerance limits its clinical efficacy of nitric oxide（NO）*** cellular mechanisms have been proposed to explain this phenomenon,one of which is an exaggerated production of reactive oxygen specious（ROS）.The present study examined whether ROS contribute to the occurrence of nitroglycerine tolerance which is induced acutely in aortas isolated from male Sprague-Dawley *** aortas were exposed to 30μmol/L nitroglycerine（with and without pre-incubation of ROS inhibitors） for 90 min and washed out 4 times during the following 60 min before phenylephrine was added to induce a steady contraction. Subsequently,nitroglycerine was added cumulatively（3 nmol/L-50μmol/L）to evoke ***-induced relaxations were severely impaired after 90-min pre-exposure to *** with apocynin,tempol and tiron plus DETCA

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Hemin restores the impaired endothelium -dependent vasodilat...

What are the ten new commandments in severe polytrauma management？

中国病理生理学会第九届全国代表大会及学术会议

作者： LIU J,WONG WT,TIAN XY,LIU LM,WONG SL,lau cw,YU J,YAO X,HUANG Y Institute of Vascular Medicine and School of Biomedical Sciences,Chinese University of Hong Kong,China

Heme oxygenase(HO)is the enzyme that catalyzes the degradation of heme and leads to the formation of carbon monoxide,free iron and *** evidence suggests that HO-1,an inducible isoform of HO,can exert vaso-protective ***, such vascular benefit in diabetic vasculopathy remains largely *** present study investigates the impact of HO-1 induction on endothelial dysfunction in type 2 diabetic db/db *** db/db and non-diabetic db/mmice were treated with hemin

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World Journal of Emergency Medicine 2010年第2期1卷 85-92页

作者： cw Kam CH Lai SK Lam FL So CL lau KH Cheung Accident ＆ Emergency Department Tuen Mun Hospital Hong Kong China

This review aims to provide a concise overview of the trauma management evolution in the past decade. 1） Trauma care priorities have incorporated staff protection against infection and early decision making in addition to the conventional ABCDE. 2） Five stratified levels for DAM have replaced the non-specific conventional Plans A ＆ B. 3） CT scanning can be the tunnel to death for the hemodynamically unstable patient. 4） DPL has virtually been replaced by the FAST USG. 5） Direct whole-body MDCT provides rapid imaging diagnosis ＆ expedites the definitive treatment but carries high radiation hazards. 6） The dynamic shock assessment by fluid resuscitation response provides more outcome-specific evaluation than the static blood volume loss model. 7） DCR comprising of permissive hypotension, hemostatic resuscitation ＆ DCS aims to overcome the lethal triad of trauma. Early transfusion of blood components of FFP ＆ platelet concentrates improves the outcome in massive blood transfusion. 8） DCS aims to rectify the deranged physiology and not to fully restore the damaged anatomy. 9） A pre-defined protocol for major pelvic fracture can be life-saving and the novel Pre-PPP （pre-peritoneal pelvic packing） may further reduce mortality coupled with the necessary TCAE. 10） Injury prevention is equally important if not more than the trauma resuscitation ＆ operation.

关键词： Polytrauma Priorities DAM CT MDCT DPL FAST Fluid resuscitation responder DCR DCS Pre-PPP Injury prevention

TURMERIC-COULD IT BE A MULTI-TARGETED HERB FOR COLORECTAL CANCER ADJUVANT THERAPY?

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World Journal of Traditional Chinese Medicine 2015年第4期1卷 74-75页

作者： Grace GL Yue Hin-Fai Kwok Julia KM Lee Lei Jiang Si Gao Carmen KM Chan Eric cw Wong Kwok-Pui Fung Ping-Chung Leung Zhong Zuo Clara BS lau Institute of Chinese Medicine State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK) School of Biomedical Sciences School of Pharmacy The Chinese University of Hong Kong

Turmeric is a medicinal herb in Asia and as dietary supplement in western *** major active component,*** good reputation for chemopreventive effects in different ***,poor oral bioavailability of curcumin hinders the w... 详细信息

关键词： TURMERIC-COULD IT BE A MULTI-TARGETED HERB FOR COLORECTAL CANCER ADJUVANT THERAPY

缺血性脑卒中患者诊间血压变异性对长期预后的影响

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中华高血压杂志 2015年第5期23卷 498-498页

作者： lau KK Wong YK Teo KC Chang RS Chan KH Hon SF Wat KL Cheung RT Li LS Siu cw Tse HF

血压变异性（blood pressure variablity，BPV）是动脉粥样硬化疾病发展的新的危险因素。最近研究显示，高BPV能预测腔隙性梗死患者的全因和心血管死亡率。除因小血管阻塞造成的脑卒中患者外，BPV是否对缺血性脑卒中患者的预后产生影响... 详细信息

血压变异性（blood pressure variablity，BPV）是动脉粥样硬化疾病发展的新的危险因素。最近研究显示，高BPV能预测腔隙性梗死患者的全因和心血管死亡率。除因小血管阻塞造成的脑卒中患者外，BPV是否对缺血性脑卒中患者的预后产生影响仍然不清楚。

关键词：脑卒中患者血压变异性长期预后缺血性动脉粥样硬化心血管死亡率腔隙性梗死危险因素