脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)是脂肪酸结合蛋白家族之一,在调控脂肪酸的摄取、运输和代谢中发挥重要作用。近年来多项研究证实,FABP5在多种肿瘤中高表达,其参与了肿瘤的增殖、转移以及诱导免疫逃逸等多种肿瘤...脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)是脂肪酸结合蛋白家族之一,在调控脂肪酸的摄取、运输和代谢中发挥重要作用。近年来多项研究证实,FABP5在多种肿瘤中高表达,其参与了肿瘤的增殖、转移以及诱导免疫逃逸等多种肿瘤生物学过程。该文综述了FABP5在肿瘤中的最新研究进展,旨在讨论FABP5在肿瘤中的作用及机制,为肿瘤相关研究提供新思路,同时为肿瘤新靶点的开发提供更多理论依据。展开更多
OBJECTIVE: To study the mechanism of Dangfei Liganning capsule(当飞利肝宁胶囊) in the treatment of rats with metabolic associated fatty liver disease(MAFLD). METHODS: Totally 48 specific pathogen free SpragueDawley ma...OBJECTIVE: To study the mechanism of Dangfei Liganning capsule(当飞利肝宁胶囊) in the treatment of rats with metabolic associated fatty liver disease(MAFLD). METHODS: Totally 48 specific pathogen free SpragueDawley male rats were randomly divided into normal Group, model group, Dangfei Liganning high, moderate, and low-dose groups and Essentiale group which were fed with high fat diet for 8 weeks, and gavage and molding were carried out simultaneously. Dangfei Liganning high, middle and low-dose group were given 0.27, 0.135 and 0.0675 g·kg-1·d-1 respectively by gavage, Essentiale group was given 0.123 g·kg-1·d-1 by gavage, the same amount of distilled water was given by gavage in the normal group and the model group. The rats were weighed at the 0th week, 2nd week, 4th week, 6th week and 8th weekend respectively. The rats were sacrificed at the end of the 8th week. Serum levels of alanine aminotransferase(ALT), alanine aminotransferase(AST),triglyceride(TG), total cholesterol(CHO), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein (LDL-C), total protein(TP), albumin(Alb), globulin(GLB), total bilirubin(TBIL), direct bilirubin(DBIL), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were measured. The levels of liver tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and liver pathology [hematoxylin and eosin(HE) staining, oil red O staining] were detected. The expression levels of liver X receptor α(LXRα), steroid regulatory element binding protein-1(SREBP-1) and fatty acid synthase(FAS) were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction reverse transcription-polymerase chain reaction. RESULTS: From the beginning to the 8th week, the growth rate of body weight in the Dangfei Liganning highdose group was slower than all other groups. There was no significant difference in ALB level in all groups(P > 0.05). Compared with the model group, the levels of ALT, AST, LDL-C, TG, CHO, TP, GLB, TBIL, DBIL, IL-6, TNF-α were significantly decreased and HDL-C were significantly increased in Dangfei Liganning high-dose group(P < 0.01, < 0.05). HE and oil red O staining showed that the fatty lesions in rat liver were alleviated, while the expressions of LXRα, SREBP-1, FAS m RNA and protein were significantly decreased(P < 0.01). CONCLUSIONS: Dangfei Liganning capsule can slow down the increase of body weight of MAFLD rats, reduce the levels of transaminase, Lipid and inflammatory factors in MAFLD rats, promote the synthesis of liver protein and bile metabolism, and improve the liver fatty lesion of MAFLD rats, among which the Dangfei Liganning highdose group is more effective. The mechanism of action may be through blocking LXR-SREBP-1-FAS signal pathway.展开更多
目的探讨脂肪酸结合蛋白5(fatty acid-binding protein 5,FABP5)与细胞维甲酸结合蛋白2(cellular retinoic acid-binding protein 2,CRABP2)在脑胶质瘤中的表达及与脑胶质瘤病理级别、维甲酸治疗抵抗的关系。方法应用免疫组织化学染色...目的探讨脂肪酸结合蛋白5(fatty acid-binding protein 5,FABP5)与细胞维甲酸结合蛋白2(cellular retinoic acid-binding protein 2,CRABP2)在脑胶质瘤中的表达及与脑胶质瘤病理级别、维甲酸治疗抵抗的关系。方法应用免疫组织化学染色法检测125例脑星型细胞瘤组织中FABP5及CRABP2蛋白表达。全反式维甲酸作用前后,以Brdu-ELISA法检测胶质瘤细胞增殖,并以实时荧光定量PCR检测胶质瘤细胞株中FABP5及CRABP2在m RNA水平的表达。结果 FABP5阳性细胞比例在WHOⅡ级星型细胞瘤中占(16±9)%,Ⅲ级中占(33±22)%,Ⅳ级中占(50±29)%,FABP5蛋白表达与胶质瘤病理级别呈显著正相关(P<0.05)。CRABP2阳性细胞比例在Ⅱ级星型细胞瘤中占(46±12)%,WHOⅢ级中占(30±15)%,Ⅳ级中占(10±9)%,CRABP2蛋白表达与胶质瘤病理级别呈显著负相关(P<0.05)。全反式维甲酸促进了胶质瘤细胞株的增殖,全反式维甲酸作用后胶质瘤细胞FABP5 m RNA表达显著上调,而CRABP2显著下调。结论 FABP5及CRABP2的异常表达与胶质瘤恶性程度相关,并可能介导了胶质瘤细胞对维甲酸的分化抵抗效应。展开更多
AIM: To evaluate the effect of resveratrol, alone and in combination with fenofibrate, on fructose-induced metabolic genes abnormalities in rats.METHODS: Giving a fructose-enriched diet (FED) to rats for 12 wk was use...AIM: To evaluate the effect of resveratrol, alone and in combination with fenofibrate, on fructose-induced metabolic genes abnormalities in rats.METHODS: Giving a fructose-enriched diet (FED) to rats for 12 wk was used as a model for inducing hepatic dyslipidemia and insulin resistance. Adult male albino rats (150-200 g) were divided into a control group and a FED group which was subdivided into 4 groups, a control FED, fenofibrate (FENO) (100 mg/kg), resveratrol (RES) (70 mg/kg) and combined treatment (FENO + RES) (half the doses). All treatments were given orally from the 9<sup>th</sup> week till the end of experimental period. Body weight, oral glucose tolerance test (OGTT), liver index, glucose, insulin, insulin resistance (HOMA), serum and liver triglycerides (TGs), oxidative stress (liver MDA, GSH and SOD), serum AST, ALT, AST/ALT ratio and tumor necrosis factor-α (TNF-α) were measured. Additionally, hepatic gene expression of suppressor of cytokine signaling-3 (SOCS-3), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), malonyl CoA decarboxylase (MCD), transforming growth factor-β1 (TGF-β1) and adipose tissue genes expression of leptin and adiponectin were investigated. Liver sections were taken for histopathological examination and steatosis area were determined.RESULTS: Rats fed FED showed damaged liver, impairment of glucose tolerance, insulin resistance, oxidative stress and dyslipidemia. As for gene expression, there was a change in favor of dyslipidemia and nonalcoholic steatohepatitis (NASH) development. All treatment regimens showed some benefit in reversing the described deviations. Fructose caused deterioration in hepatic gene expression of SOCS-3, SREBP-1c, FAS, MDA and TGF-β1 and in adipose tissue gene expression of leptin and adiponectin. Fructose showed also an increase in body weight, insulin resistance (OGTT, HOMA), serum and liver TGs, hepatic MDA, serum AST, AST/ALT ratio and TNF-α compared to control. All treatments improved SOCS-3, FAS, MCD, TGF-β1 and leptin genes expression while only RES and FENO + RES groups showed an improvement in SREBP-1c expression. Adiponectin gene expression was improved only by RES. A decrease in body weight, HOMA, liver TGs, AST/ALT ratio and TNF-α were observed in all treatment groups. Liver index was increased in FENO and FENO + RES groups. Serum TGs was improved only by FENO treatment. Liver MDA was improved by RES and FENO + RES treatments. FENO + RES group showed an increase in liver GSH content.CONCLUSION: When resveratrol was given with half the dose of fenofibrate it improved NASH-related fructose-induced disturbances in gene expression similar to a full dose of fenofibrate.展开更多
文摘脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)是脂肪酸结合蛋白家族之一,在调控脂肪酸的摄取、运输和代谢中发挥重要作用。近年来多项研究证实,FABP5在多种肿瘤中高表达,其参与了肿瘤的增殖、转移以及诱导免疫逃逸等多种肿瘤生物学过程。该文综述了FABP5在肿瘤中的最新研究进展,旨在讨论FABP5在肿瘤中的作用及机制,为肿瘤相关研究提供新思路,同时为肿瘤新靶点的开发提供更多理论依据。
基金Supported by Capital Health Development Research Project:Assessment of the Efficacy of BIEJIAJIANWAN Pill in Patients with Chronic Hepatitis B Cirrhosis/Fibrosis (CD2018-2-2173)Beijing Municipal Administration of Hospitals Incubating Program:Clinical Observation on the Treatment of Nonalcoholic Fatty Liver Disease by Invigorating the Spleen,Soothing the Liver,Activating Blood Circulation and Resolving Phlegm (PZ2019011)。
文摘OBJECTIVE: To study the mechanism of Dangfei Liganning capsule(当飞利肝宁胶囊) in the treatment of rats with metabolic associated fatty liver disease(MAFLD). METHODS: Totally 48 specific pathogen free SpragueDawley male rats were randomly divided into normal Group, model group, Dangfei Liganning high, moderate, and low-dose groups and Essentiale group which were fed with high fat diet for 8 weeks, and gavage and molding were carried out simultaneously. Dangfei Liganning high, middle and low-dose group were given 0.27, 0.135 and 0.0675 g·kg-1·d-1 respectively by gavage, Essentiale group was given 0.123 g·kg-1·d-1 by gavage, the same amount of distilled water was given by gavage in the normal group and the model group. The rats were weighed at the 0th week, 2nd week, 4th week, 6th week and 8th weekend respectively. The rats were sacrificed at the end of the 8th week. Serum levels of alanine aminotransferase(ALT), alanine aminotransferase(AST),triglyceride(TG), total cholesterol(CHO), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein (LDL-C), total protein(TP), albumin(Alb), globulin(GLB), total bilirubin(TBIL), direct bilirubin(DBIL), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were measured. The levels of liver tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and liver pathology [hematoxylin and eosin(HE) staining, oil red O staining] were detected. The expression levels of liver X receptor α(LXRα), steroid regulatory element binding protein-1(SREBP-1) and fatty acid synthase(FAS) were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction reverse transcription-polymerase chain reaction. RESULTS: From the beginning to the 8th week, the growth rate of body weight in the Dangfei Liganning highdose group was slower than all other groups. There was no significant difference in ALB level in all groups(P > 0.05). Compared with the model group, the levels of ALT, AST, LDL-C, TG, CHO, TP, GLB, TBIL, DBIL, IL-6, TNF-α were significantly decreased and HDL-C were significantly increased in Dangfei Liganning high-dose group(P < 0.01, < 0.05). HE and oil red O staining showed that the fatty lesions in rat liver were alleviated, while the expressions of LXRα, SREBP-1, FAS m RNA and protein were significantly decreased(P < 0.01). CONCLUSIONS: Dangfei Liganning capsule can slow down the increase of body weight of MAFLD rats, reduce the levels of transaminase, Lipid and inflammatory factors in MAFLD rats, promote the synthesis of liver protein and bile metabolism, and improve the liver fatty lesion of MAFLD rats, among which the Dangfei Liganning highdose group is more effective. The mechanism of action may be through blocking LXR-SREBP-1-FAS signal pathway.
文摘目的探讨脂肪酸结合蛋白5(fatty acid-binding protein 5,FABP5)与细胞维甲酸结合蛋白2(cellular retinoic acid-binding protein 2,CRABP2)在脑胶质瘤中的表达及与脑胶质瘤病理级别、维甲酸治疗抵抗的关系。方法应用免疫组织化学染色法检测125例脑星型细胞瘤组织中FABP5及CRABP2蛋白表达。全反式维甲酸作用前后,以Brdu-ELISA法检测胶质瘤细胞增殖,并以实时荧光定量PCR检测胶质瘤细胞株中FABP5及CRABP2在m RNA水平的表达。结果 FABP5阳性细胞比例在WHOⅡ级星型细胞瘤中占(16±9)%,Ⅲ级中占(33±22)%,Ⅳ级中占(50±29)%,FABP5蛋白表达与胶质瘤病理级别呈显著正相关(P<0.05)。CRABP2阳性细胞比例在Ⅱ级星型细胞瘤中占(46±12)%,WHOⅢ级中占(30±15)%,Ⅳ级中占(10±9)%,CRABP2蛋白表达与胶质瘤病理级别呈显著负相关(P<0.05)。全反式维甲酸促进了胶质瘤细胞株的增殖,全反式维甲酸作用后胶质瘤细胞FABP5 m RNA表达显著上调,而CRABP2显著下调。结论 FABP5及CRABP2的异常表达与胶质瘤恶性程度相关,并可能介导了胶质瘤细胞对维甲酸的分化抵抗效应。
文摘AIM: To evaluate the effect of resveratrol, alone and in combination with fenofibrate, on fructose-induced metabolic genes abnormalities in rats.METHODS: Giving a fructose-enriched diet (FED) to rats for 12 wk was used as a model for inducing hepatic dyslipidemia and insulin resistance. Adult male albino rats (150-200 g) were divided into a control group and a FED group which was subdivided into 4 groups, a control FED, fenofibrate (FENO) (100 mg/kg), resveratrol (RES) (70 mg/kg) and combined treatment (FENO + RES) (half the doses). All treatments were given orally from the 9<sup>th</sup> week till the end of experimental period. Body weight, oral glucose tolerance test (OGTT), liver index, glucose, insulin, insulin resistance (HOMA), serum and liver triglycerides (TGs), oxidative stress (liver MDA, GSH and SOD), serum AST, ALT, AST/ALT ratio and tumor necrosis factor-α (TNF-α) were measured. Additionally, hepatic gene expression of suppressor of cytokine signaling-3 (SOCS-3), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), malonyl CoA decarboxylase (MCD), transforming growth factor-β1 (TGF-β1) and adipose tissue genes expression of leptin and adiponectin were investigated. Liver sections were taken for histopathological examination and steatosis area were determined.RESULTS: Rats fed FED showed damaged liver, impairment of glucose tolerance, insulin resistance, oxidative stress and dyslipidemia. As for gene expression, there was a change in favor of dyslipidemia and nonalcoholic steatohepatitis (NASH) development. All treatment regimens showed some benefit in reversing the described deviations. Fructose caused deterioration in hepatic gene expression of SOCS-3, SREBP-1c, FAS, MDA and TGF-β1 and in adipose tissue gene expression of leptin and adiponectin. Fructose showed also an increase in body weight, insulin resistance (OGTT, HOMA), serum and liver TGs, hepatic MDA, serum AST, AST/ALT ratio and TNF-α compared to control. All treatments improved SOCS-3, FAS, MCD, TGF-β1 and leptin genes expression while only RES and FENO + RES groups showed an improvement in SREBP-1c expression. Adiponectin gene expression was improved only by RES. A decrease in body weight, HOMA, liver TGs, AST/ALT ratio and TNF-α were observed in all treatment groups. Liver index was increased in FENO and FENO + RES groups. Serum TGs was improved only by FENO treatment. Liver MDA was improved by RES and FENO + RES treatments. FENO + RES group showed an increase in liver GSH content.CONCLUSION: When resveratrol was given with half the dose of fenofibrate it improved NASH-related fructose-induced disturbances in gene expression similar to a full dose of fenofibrate.