HIF-1α和Hsp90抑制劑對福美雙誘導的脛骨軟骨發(fā)育不良肉雞生長板功能恢復的影響
發(fā)布時間：2019-05-26 21:48
【摘要】：肉雞脛骨軟骨發(fā)育不良(Tibial dyschondroplasia,TD)是一種以生長板無血管化和無礦化為特征的重要家禽脛跗骨疾病。它主要引起軟骨細胞的異常分化和家禽的跛行,從而降低動物的生長性能,對家禽業(yè)造成巨大的經(jīng)濟損失。1.HIF-1ɑ抑制劑在福美雙誘導的TD上的作用本研究旨在評估缺氧誘導因子-1α(Hypoxia-Inducible Factor-1α,HIF-1ɑ)抑制劑FK228在福美雙誘導的TD上的作用和HIF-1ɑ和Hsp90之間的關系。將150只肉雞隨機分成3組:對照組、福美雙組、FK228組。通過RT-qPCR檢測第10天和14天HIF-1ɑ、Hsp90和血管內皮生長因子(vascular endothelial growth factor,VEGF)基因的表達;Western blot檢測第14天HIF-1ɑ和Hsp90蛋白表達水平。結果顯示:在TD病程中HIF-1ɑ顯著上調(P0.05),VEGF沒有顯示變化(p0.05)。HIF-1ɑ抑制劑能夠顯著下調HIF-1ɑ和VEGF基因的表達和蛋白的表達水平(P0.05),從而減少生長板的尺寸和肉雞的跛行。綜上所述,HIF-1ɑ和VEGF在肉雞脛骨軟骨發(fā)育不良非血管化的生長板上在形成中起著重要作用,這可能就是作為防治肉雞無血管化生長板和跛行的HIF-1ɑ抑制因子作用的靶點。HIF-1ɑ抑制因子可以作為預防肉雞脛骨軟骨生長板無血管化、生長跛行和恢復生長板血管生成的新靶標。2.Hsp90抑制劑EGCG和芹黃素在肉雞脛骨軟骨發(fā)育不良上具有治愈生長板的作用熱休克蛋白90(Heat-shock protein 90,Hsp90)在動物組織中是一種前血管生長因子,研究表明在肉雞TD的病例中Hsp90表達量增加。本研究旨在評估Hsp90抑制劑表沒食子兒茶素沒食子酸酯(EGCG)和芹黃素在福美雙誘導的肉雞TD中的作用。本研究采用HE對生長板進行組織學觀察,RT-qPCR檢測Hsp90基因的表達量。結果表明:肉雞TD的發(fā)生伴隨血管減少,軟骨細胞分化發(fā)生改變,Hsp90表達量顯著增加(P0.05)。然而,TD肉雞給予EGCG和芹黃素后發(fā)現(xiàn)軟骨細胞柱狀組織修復和Hsp90表達活性被降低(P0.05),最終跛行消失。結果表明Hsp90是TD發(fā)生的一個關鍵因素;EGCG和芹黃素通過抑制Hsp90基因的表達來有效的治療TD,減少跛行和肉雞腿的畸形。3.HIF-1α抑制劑Apigenin在生長板軟骨治愈上的作用本研究旨在了解缺氧誘導因子(HIF-1α)抑制劑的機制和芹黃素在福美雙誘導TD上的抗氧化能力。將150只肉雞隨機分為3組:對照組、福美雙組、芹黃素組。分別于試驗的第10天和第14天采用RT-qPCR方法對HIF-1ɑ基因表達量進行檢測。結果表明:與對照組相比,HIF-1ɑ基因表達量在福美雙誘發(fā)TD期間顯著上調(P0.05);芹黃素組HIF-1ɑ表達量顯著下調(P0.05),生長板尺寸和跛行減少。另外,福美雙誘導肝臟中天冬氨酸氨基轉移酶(AST)、丙氨酸氨基轉移酶(ALT)和丙二醛(MDA)含量的增加,而福美雙組抗氧化酶(SOD;GSH-Px)和堿性磷酸酶(ALP)值降低;而芹黃素組各項指標均接近正常組。結果表明:HIF-1ɑ抑制劑能夠恢復肉雞跛行和非血管化的生長板,且芹黃素能夠有效的改善福美雙引起的肝臟損傷和氧化失衡。
[Abstract]:Dystrophy of tibia cartilage (Tibial dyschondroplasia,TD) in broilers is an important disease of tibia and tarsal bone in poultry characterized by non-vascularization and mineralization of growth plate. It mainly causes the abnormal differentiation of cartilage cells and the claudication of poultry, thus reducing the growth performance of animals. The effect of HIF-1 inhibitor on TD induced by Fumei Shuang was studied in order to evaluate hypoxia-inducible factor-1 偽 (Hypoxia-Inducible Factor-1 偽). 1. The effect of HIF-1 inhibitor on Fumei-induced HIF-1 偽 was studied in order to evaluate hypoxia-induced factor-1 偽 (HIF-偽). The role of FK228, an inhibitor of HIF-1, in TD induced by Fumibi and the relationship between HIF-1 and Hsp90. 150 broilers were randomly divided into three groups: control group, Fumei group and FK228 group. The expression of HIF-1, Hsp90 and vascular endothelial growth factor (vascular endothelial growth factor,VEGF (vascular endothelial growth factor,VEGF) genes on the 10th and 14th day were detected by RT-qPCR. The expression levels of HIF-1 and Hsp90 proteins on the 14th day were detected by; Western blot. The results showed that HIF-1 was significantly up-regulated in the course of TD (p0.05). HIF-1 inhibitor could significantly down-regulate the expression of HIF-1 and VEGF genes and the expression of protein (P 0.05). Thus reducing the size of the growth board and the limp of broilers. To sum up, HIF-1 and VEGF play an important role in the formation of non-vascularized growth plates with dysplasia of tibia in broilers. This may be the target for the prevention and treatment of avascularization growth plate and claudication inhibitor of HIF-1 in broilers. HIF-1 inhibitor can be used to prevent the absence of vascularization of tibia cartilage growth plate in broilers. A new target for growth claudication and recovery of growth plate vascularization. 2. Hsp90 inhibitor EGCG and celery can cure growth plate heat shock protein 90 (Heat-shock protein 90) in broilers with dystrophy of tibia cartilage. Hsp90) is a pre-vascular growth factor in animal tissues. Studies have shown that the expression of Hsp90 is increased in broilers with TD. The purpose of this study was to evaluate the role of Hsp90 inhibitors epigallocatechin gallate (EGCG) and celery in TD induced by Fu Mei Shuang. In this study, HE was used to observe the histology of the growth plate, and the expression of Hsp90 gene was detected by RT-qPCR. The results showed that the occurrence of TD in broilers was accompanied by the decrease of blood vessels, the differentiation of cartilage cells and the increase of Hsp90 expression (P 0.05). However, after administration of EGCG and celery in TD broilers, it was found that the columnar tissue repair and Hsp90 expression activity of cartilage cells were decreased (P 0.05), and finally limp disappeared. The results showed that Hsp90 was a key factor in the occurrence of TD. EGCG and celery can effectively treat TD, by inhibiting the expression of Hsp90 gene. 3. The role of Apigenin, an inhibitor of HIF-1 偽, in the healing of growth plate cartilage. The purpose of this study was to investigate the mechanism of hypoxia inducible factor 偽 (HIF-1 偽) inhibitor and the antioxidant capacity of celery on Fumei induced TD. 150 broilers were randomly divided into three groups: control group, Fumei group and celery group. The expression of HIF-1 gene was detected by RT-qPCR on the 10th and 14th day of the experiment, respectively. The results showed that compared with the control group, the expression of HIF-1 gene was significantly up-regulated during TD induced by Fu Mei Shuang (P 0.05), while the expression of HIF-1 in celery group was significantly down-regulated (P 0.05), and the size of growth plate and claudication were decreased. In addition, the contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) in liver were increased, while the (ALP) values of antioxidant enzymes (SOD;GSH-Px) and alkaline phosphatase were decreased. However, all the indexes in celery group were close to those in normal group. The results showed that HIF-1 inhibitor could restore limp and non-vascularization growth plate in broilers, and celery could effectively improve liver injury and oxidative imbalance induced by Fu Mei Shuang.
【學位授予單位】：華中農業(yè)大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：S858.31
本文編號：2485660
[Abstract]:Dystrophy of tibia cartilage (Tibial dyschondroplasia,TD) in broilers is an important disease of tibia and tarsal bone in poultry characterized by non-vascularization and mineralization of growth plate. It mainly causes the abnormal differentiation of cartilage cells and the claudication of poultry, thus reducing the growth performance of animals. The effect of HIF-1 inhibitor on TD induced by Fumei Shuang was studied in order to evaluate hypoxia-inducible factor-1 偽 (Hypoxia-Inducible Factor-1 偽). 1. The effect of HIF-1 inhibitor on Fumei-induced HIF-1 偽 was studied in order to evaluate hypoxia-induced factor-1 偽 (HIF-偽). The role of FK228, an inhibitor of HIF-1, in TD induced by Fumibi and the relationship between HIF-1 and Hsp90. 150 broilers were randomly divided into three groups: control group, Fumei group and FK228 group. The expression of HIF-1, Hsp90 and vascular endothelial growth factor (vascular endothelial growth factor,VEGF (vascular endothelial growth factor,VEGF) genes on the 10th and 14th day were detected by RT-qPCR. The expression levels of HIF-1 and Hsp90 proteins on the 14th day were detected by; Western blot. The results showed that HIF-1 was significantly up-regulated in the course of TD (p0.05). HIF-1 inhibitor could significantly down-regulate the expression of HIF-1 and VEGF genes and the expression of protein (P 0.05). Thus reducing the size of the growth board and the limp of broilers. To sum up, HIF-1 and VEGF play an important role in the formation of non-vascularized growth plates with dysplasia of tibia in broilers. This may be the target for the prevention and treatment of avascularization growth plate and claudication inhibitor of HIF-1 in broilers. HIF-1 inhibitor can be used to prevent the absence of vascularization of tibia cartilage growth plate in broilers. A new target for growth claudication and recovery of growth plate vascularization. 2. Hsp90 inhibitor EGCG and celery can cure growth plate heat shock protein 90 (Heat-shock protein 90) in broilers with dystrophy of tibia cartilage. Hsp90) is a pre-vascular growth factor in animal tissues. Studies have shown that the expression of Hsp90 is increased in broilers with TD. The purpose of this study was to evaluate the role of Hsp90 inhibitors epigallocatechin gallate (EGCG) and celery in TD induced by Fu Mei Shuang. In this study, HE was used to observe the histology of the growth plate, and the expression of Hsp90 gene was detected by RT-qPCR. The results showed that the occurrence of TD in broilers was accompanied by the decrease of blood vessels, the differentiation of cartilage cells and the increase of Hsp90 expression (P 0.05). However, after administration of EGCG and celery in TD broilers, it was found that the columnar tissue repair and Hsp90 expression activity of cartilage cells were decreased (P 0.05), and finally limp disappeared. The results showed that Hsp90 was a key factor in the occurrence of TD. EGCG and celery can effectively treat TD, by inhibiting the expression of Hsp90 gene. 3. The role of Apigenin, an inhibitor of HIF-1 偽, in the healing of growth plate cartilage. The purpose of this study was to investigate the mechanism of hypoxia inducible factor 偽 (HIF-1 偽) inhibitor and the antioxidant capacity of celery on Fumei induced TD. 150 broilers were randomly divided into three groups: control group, Fumei group and celery group. The expression of HIF-1 gene was detected by RT-qPCR on the 10th and 14th day of the experiment, respectively. The results showed that compared with the control group, the expression of HIF-1 gene was significantly up-regulated during TD induced by Fu Mei Shuang (P 0.05), while the expression of HIF-1 in celery group was significantly down-regulated (P 0.05), and the size of growth plate and claudication were decreased. In addition, the contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) in liver were increased, while the (ALP) values of antioxidant enzymes (SOD;GSH-Px) and alkaline phosphatase were decreased. However, all the indexes in celery group were close to those in normal group. The results showed that HIF-1 inhibitor could restore limp and non-vascularization growth plate in broilers, and celery could effectively improve liver injury and oxidative imbalance induced by Fu Mei Shuang.
【學位授予單位】：華中農業(yè)大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：S858.31
【參考文獻】
相關期刊論文 前1條
1 Georgina N.Masoud;Wei Li;;HIF-1α pathway: role, regulation and intervention for cancer therapy[J];Acta Pharmaceutica Sinica B;2015年05期
，本文編號：2485660
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