Rho A/ROCK信号转导通路在肝纤维化中的作用及法舒地尔的肝脏保护机制研究
发布时间：2021-03-31 06:39
肝纤维化（hepatic fibrosis）是多种病因所致的慢性肝损伤的修复反应,是慢性肝病转化为肝硬化和肝功能衰竭的必经阶段和共同病理基础,因此,预防、治疗甚至逆转肝纤维化是阻断肝硬化的关键环节。研究证实肝纤维化是由于胶原合成、沉积与降解和吸收的动态平衡被破坏,使胶原的合成与沉积大于降解和吸收,致使细胞外基质（extracellularmatrix,ECM）过度沉积为典型特征,在这一过程中炎症反应、氧化应激、免疫反应和细胞凋亡等病理生理过程发挥了重要的作用。我国是肝病高发国家,目前尚无有效的抗肝病药物,如何阻止或逆转ECM过度沉积成为治疗慢性肝病的关键,也是国内外学者的研究重点。Rho蛋白作为小分子的鸟苷酸结合蛋白,属于Ras超家族成员,被称为“分子开关”。ROCK是Rho A下游最主要的效应分子,是丝氨酸/苏氨酸（Ser/Thr）蛋白激酶家族成员。近年来研究发现,激活的Rho A/ROCK信号转导通路能够介导细胞粘附与迁移、肌动蛋白骨架形成及细胞增殖和凋亡等多种生物学功能,这些效应在多种器官组织慢性炎症纤维化中发挥了重大作用。有研究表明,选择性阻断该信号通路可以改善纤维化器官的进展...
【文章来源】：河北医科大学河北省
【文章页数】：131 页
【学位级别】：博士
【部分图文】：
肝脏组织病理变化（H&E染色）
图 2 肝脏组织病理变化（Masson 染色）Fig. 2 Effects of fasudil on hepatic fibrosis as assessed by staining withMasson's trichrome.Representative microscopic photographs of liver stained with Masson's trichrome (400×magnification). Livers were obtained from the normal control (NC), untreated diabetic(DM), low-dose fasudil-treated (L-Fas), high-dose fasudil-treated (H-Fas), and captopril-treated (Cap) groups. Scale bar, 50 μm.#P < 0.05 vs. control group;##P < 0.01 vs. controlgroup; *P < 0.05 vs. DM group; **P < 0.01 vs. DM group; n = 10.
图 3 大鼠肝脏组织 TGF- 1、MMP-9、TIMP-1、 NF-κB p65 及 IκB蛋白含量变化情况Fig. 3 TGF- 1, MMP-9, TIMP-1, NF-κB p65 and IκB protein levels in ratlivers treated with fasudil.Livers were obtained from the normal control (NC), untreated diabetic (DM), low-dosefasudil-treated (L-Fas), high-dose fasudil-treated (H-Fas), and captopril-treated (Cap)groups. Intensities of target proteins were standardized to that of β-actin. The proportionshowed in the histogram below the target bands. Results are expressed as the mean ±SEM.#P < 0.05 vs. control group;##P < 0.01 vs. control group; *P < 0.05 vs. DM group; **P <0.01 vs. DM group; n = 10.
【参考文献】：
期刊论文
[1]影响2型糖尿病患者新发非酒精性脂肪肝相关因素分析[J]. 阎劲松,袁丹,李东升. 实用肝脏病杂志. 2016(02)
[2]法舒地尔对早期糖尿病肾病患者氧化应激的影响[J]. 徐美荣,吴甘霖. 实用医学杂志. 2015(08)
[3]法舒地尔抑制氧化应激反应减轻2型糖尿病大鼠心肌纤维化[J]. 李贵芝,周红,房彩霞,张力辉,王绵,王瑞英. 基础医学与临床. 2014(02)
[4]法舒地尔抗动脉粥样硬化作用及其机制[J]. 武多娇,张怡,高平进,朱鼎良. 中国临床药学杂志. 2010(02)
[5]大鼠免疫性与淤胆性肝纤维化发病机制比较[J]. 何瑶,陈白莉,杨荣萍,任明,曾志荣. 南方医科大学学报. 2010(02)
[6]肝纤维化动物模型探讨[J]. 周贤,刘翼,夏国栋,邵泽勇. 四川动物. 2010(01)
[7]Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis[J]. Eugen Florin Georgescu,Reanina Ionescu,Mihaela Niculescu,Laurentiu Mogoanta,Liliana Vancica. World Journal of Gastroenterology. 2009(08)
[8]异丙酚对离体大鼠心肌缺血/再灌注损伤后细胞凋亡及其机制研究[J]. 解丽君,张建新,李兰芳. 中国应用生理学杂志. 2008(01)
[9]氧化应激的病理生理作用[J]. 光吉博則,谷仁烨. 日本医学介绍. 2007(04)
[10]Inhibitory effect of angiotensinⅡreceptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis[J]. Shiro Yokohama,Yoshihiko Tokusashi,Kimihide Nakamura,Yosui Tamaki,Satoshi Okamoto,Mituyoshi Okada,Kazunobu Aso,Takenao Hasegawa,Masaru Aoshima,Naoyuki Miyokawa,Masakazu Haneda,Masashi Yoneda. World Journal of Gastroenterology. 2006(02)
本文编号：3110985
【文章来源】：河北医科大学河北省
【文章页数】：131 页
【学位级别】：博士
【部分图文】：
肝脏组织病理变化（H&E染色）
图 2 肝脏组织病理变化（Masson 染色）Fig. 2 Effects of fasudil on hepatic fibrosis as assessed by staining withMasson's trichrome.Representative microscopic photographs of liver stained with Masson's trichrome (400×magnification). Livers were obtained from the normal control (NC), untreated diabetic(DM), low-dose fasudil-treated (L-Fas), high-dose fasudil-treated (H-Fas), and captopril-treated (Cap) groups. Scale bar, 50 μm.#P < 0.05 vs. control group;##P < 0.01 vs. controlgroup; *P < 0.05 vs. DM group; **P < 0.01 vs. DM group; n = 10.
图 3 大鼠肝脏组织 TGF- 1、MMP-9、TIMP-1、 NF-κB p65 及 IκB蛋白含量变化情况Fig. 3 TGF- 1, MMP-9, TIMP-1, NF-κB p65 and IκB protein levels in ratlivers treated with fasudil.Livers were obtained from the normal control (NC), untreated diabetic (DM), low-dosefasudil-treated (L-Fas), high-dose fasudil-treated (H-Fas), and captopril-treated (Cap)groups. Intensities of target proteins were standardized to that of β-actin. The proportionshowed in the histogram below the target bands. Results are expressed as the mean ±SEM.#P < 0.05 vs. control group;##P < 0.01 vs. control group; *P < 0.05 vs. DM group; **P <0.01 vs. DM group; n = 10.
【参考文献】：
期刊论文
[1]影响2型糖尿病患者新发非酒精性脂肪肝相关因素分析[J]. 阎劲松,袁丹,李东升. 实用肝脏病杂志. 2016(02)
[2]法舒地尔对早期糖尿病肾病患者氧化应激的影响[J]. 徐美荣,吴甘霖. 实用医学杂志. 2015(08)
[3]法舒地尔抑制氧化应激反应减轻2型糖尿病大鼠心肌纤维化[J]. 李贵芝,周红,房彩霞,张力辉,王绵,王瑞英. 基础医学与临床. 2014(02)
[4]法舒地尔抗动脉粥样硬化作用及其机制[J]. 武多娇,张怡,高平进,朱鼎良. 中国临床药学杂志. 2010(02)
[5]大鼠免疫性与淤胆性肝纤维化发病机制比较[J]. 何瑶,陈白莉,杨荣萍,任明,曾志荣. 南方医科大学学报. 2010(02)
[6]肝纤维化动物模型探讨[J]. 周贤,刘翼,夏国栋,邵泽勇. 四川动物. 2010(01)
[7]Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis[J]. Eugen Florin Georgescu,Reanina Ionescu,Mihaela Niculescu,Laurentiu Mogoanta,Liliana Vancica. World Journal of Gastroenterology. 2009(08)
[8]异丙酚对离体大鼠心肌缺血/再灌注损伤后细胞凋亡及其机制研究[J]. 解丽君,张建新,李兰芳. 中国应用生理学杂志. 2008(01)
[9]氧化应激的病理生理作用[J]. 光吉博則,谷仁烨. 日本医学介绍. 2007(04)
[10]Inhibitory effect of angiotensinⅡreceptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis[J]. Shiro Yokohama,Yoshihiko Tokusashi,Kimihide Nakamura,Yosui Tamaki,Satoshi Okamoto,Mituyoshi Okada,Kazunobu Aso,Takenao Hasegawa,Masaru Aoshima,Naoyuki Miyokawa,Masakazu Haneda,Masashi Yoneda. World Journal of Gastroenterology. 2006(02)
本文编号：3110985
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