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沉默信息调节因子1激活剂SRT1720减轻大鼠急性颅脑损伤的机制 被引量:1
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作者 钱龙杰 苏文利 +1 位作者 朱文献 王毅鑫 《中国组织工程研究》 CAS 北大核心 2024年第28期4447-4454,共8页
背景:有研究显示在急性颅脑损伤小鼠模型中,以药物激活沉默信息调节因子1的转录和翻译水平后能明显升高脑组织中沉默信息调节因子1的表达,降低脑组织炎症应激和氧化应激水平,改善神经功能。目的:探讨腹腔注射沉默信息调节因子1激活剂SRT... 背景:有研究显示在急性颅脑损伤小鼠模型中,以药物激活沉默信息调节因子1的转录和翻译水平后能明显升高脑组织中沉默信息调节因子1的表达,降低脑组织炎症应激和氧化应激水平,改善神经功能。目的:探讨腹腔注射沉默信息调节因子1激活剂SRT1720减轻大鼠急性颅脑损伤的机制。方法:取90只SD大鼠,采用随机数字表法分为3组,每组30只:假手术组不造模;模型组、激活剂组建立急性颅脑损伤模型,6 h后假手术组、模型组、激活剂组分别腹腔注射二甲亚砜溶液、二甲亚砜溶液、SRT1720,1次/d,连续注射28 d。设定取材时间点,检测大鼠神经功能、脑组织含水量、脑组织氧化应激与炎症反应、脑组织形态、细胞凋亡与血管新生以及脑组织中沉默信息调节因子1蛋白表达。结果与结论:①注射7,14,28 d时,与假手术组比较,模型组大鼠改良神经功能缺损评分、脑组织含水量及细胞凋亡率均升高(P<0.05);与模型组比较,激活剂组大鼠改良神经功能缺损评分、脑组织含水量及细胞凋亡率均降低(P<0.05);②注射7,14,28 d时,与假手术组比较,模型组大鼠脑组织中活性氧自由基、髓过氧化物酶水平升高(P<0.05),血清中丙二醛、肿瘤坏死因子α和白细胞介素6水平升高(P<0.05),血清中超氧化物歧化酶水平降低(P<0.05);与模型组比较,激活剂组大鼠大鼠脑组织中活性氧自由基、髓过氧化物酶水平降低(P<0.05),血清中丙二醛、肿瘤坏死因子α和白细胞介素6水平降低(P<0.05),血清中超氧化物歧化酶水平升高(P<0.05);③注射7,14,28 d的免疫组化染色显示,模型组大鼠脑组织中新生血管数量多于假手术组(P<0.05),激活剂组大鼠脑组织中新生血管数量多于模型组(P<0.05);注射7,14,28 d的Western blot检测显示,模型组大鼠脑组织中沉默信息调节因子1蛋白表达低于假手术组(P<0.05),激活剂组大鼠脑组织中沉默信息调节因子1蛋白表达高于模型组(P<0.05);注射7,14,28 d的苏木精-伊红染色显示,激活剂组大鼠脑组织损伤程度轻于模型组;④结果表明,腹腔注射SRT1720通过下调急性颅脑损伤大鼠脑组织氧化和炎性应激水平、抑制神经细胞凋亡、促进血管新生来减轻脑组织损伤。 展开更多
关键词 沉默信息调节因子1信号 急性颅脑损伤 氧化 炎症性应激 细胞凋亡
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Role of microglial polarization in age-related macular degeneration
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作者 Zhang Yichi Yang Xiuxia +4 位作者 Liu Pingping Liu Mengjie Luo Wenting Liu Yang Yang Chengcheng 《国际眼科杂志》 CAS 2024年第12期1863-1872,共10页
Microglia,originating from primitive macrophages in the yolk sac,serves as both immune system defenders and regulators of homeostasis.These cells exhibit two primary polarization states:conventionally activated(M1)and... Microglia,originating from primitive macrophages in the yolk sac,serves as both immune system defenders and regulators of homeostasis.These cells exhibit two primary polarization states:conventionally activated(M1)and alternatively activated(M2).The polarization of microglia plays a crucial role in influencing inflammatory disorders,metabolic imbalances,and neural degeneration.This process is implicated in various aspects of ocular diseases,especially age-related macular degeneration(AMD),including inflammation,oxidative stress and pathological angiogenesis.The distinct functional phenotypes of microglia impact disease progression and prognosis.Thus,regulating the polarization or functional phenotype of microglia at different stages of AMD holds promise for personalized therapeutic approaches.This comprehensive review outlines the involvement of microglia polarization in both physiological and pathological conditions,emphasizing its relevance in AMD.The discussion underscores the potential of polarization as a foundation for personalized treatment strategies for AMD. 展开更多
关键词 microglia polarization choroidal neovascularization INFLAMMATION oxidative stress macular degeneration
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JNKs,insulin resistance and inflammation:A possible link between NAFLD and coronary artery disease 被引量:22
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作者 Giovanni Tarantino Armando Caputi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第33期3785-3794,共10页
The incidence of obesity has dramatically increased in recent years.Consequently,obesity and associated disorders such as nonalcoholic fatty liver disease constitute a serious problem.Therefore,the contribution of adi... The incidence of obesity has dramatically increased in recent years.Consequently,obesity and associated disorders such as nonalcoholic fatty liver disease constitute a serious problem.Therefore,the contribution of adipose tissue to metabolic homeostasis has become a focus of interest.In this review,we discuss the latest discoveries that support the role of lipids in nonalcoholic fatty liver disease.We describe the common mechanisms(cJun aminoterminal kinases,endoplasmic reticulum stress,unfolded protein response,ceramide,lowgrade chronic inflammation)by which lipids and their derivatives impair insulin responsiveness and contribute to inflammatory liver and promote plaque instability in the arterial wall.Presenting the molecular mechanism of lipid activation of proinflammatory pathways,we attempt to find a link between nonalcoholic fatty liver disease,metabolic syndrome and cardiovascular diseases.Describing the common mechanisms by which lipid derivatives,through modulation of macrophage function,promote plaque instability in the arterial wall,impair insulin responsiveness and contribute to inflammatory liver and discussing the molecular mechanism of lipid activation of proinflammatory pathways,the key roles played by the proliferatoractivated receptor and liver X receptorα,nuclear receptorslipid sensors that link lipid metabolism and inflammation,should be emphasized.Further studies are warranted of antiinflammatory drugs such as aspirin,antiinterleukin6 receptors,immunemodulators(calcineurin inhibitors),substances enhancing the expression of heat shock proteins(which protect cells from endoplasmic reticulum stressinduced apoptosis),and anticJun aminoterminal kinases in welldesigned trials to try to minimize the high impact of these illnesses,and the different expressions of the diseases,on the whole population. 展开更多
关键词 Nonalcoholic fatty liver disease cJun aminoterminal kinase Cardiovascular disease
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