Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats.
Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats.
复制标题
抗原亲和纯化的多克隆抗晚期糖基化终产物受体（RAGE）抗体对胆汁淤积所致大鼠肝损伤的治疗作用。
DOI：
10.1016/j.ejphar.2016.03.017
复制
发表时间：
2016
影响因子：
5
通讯作者：
Yan Yu
中科院分区：
文献类型：
--
作者：
P. Xia;Q. Deng;Jin Gao;Xiaolan Yu;Yang Zhang;Jingjing Li;W. Guan;Jianjun Hu;Quanhui Tan;Liang Zhou;W. Han;Y. Yuan;Yan Yu
胆汁淤积导致急性肝损伤、纤维化/肝硬化、炎症和导管增殖。我们研究了用多克隆抗 RAGE 抗体 (anti-RAGE) 阻断晚期糖基化终末产物 (RAGE) 受体是否可以调节大鼠胆管结扎 (BDL) 模型中的急性肝损伤和纤维化。雄性 Wister 大鼠在 BDL 后每周两次皮下注射 0.5 mg/kg 兔抗 RAGE 或等量兔 IgG。 BDL后14天收集肝组织和外周血样本。通过血清生化和组织学分析肝损伤程度。采用实时定量PCR（qPCR）和免疫组织化学染色进一步分析肝损伤。抗RAGE改善了肝脏的总体外观和大鼠的存活率。肝组织组织学和相关血清生化表明，抗 RAGE 药物可减轻 BDL 模型中的肝坏死、炎症、肝纤维化和导管增殖。 qPCR 和蛋白质印迹显示，抗 RAGE 治疗后肝脏中白细胞介素 1β 的表达水平显着降低。 Anti-RAGE 还显着降低了 α1(1) 胶原蛋白 (Col1α1) 和胆固醇 7α-羟化酶的 mRNA 水平，以及肝脏中基质金属蛋白酶-1 组织抑制剂与基质金属蛋白酶 (MMP) 的比率。此外，抗RAGE在体外调节转化生长因子-β诱导的活化LX-2细胞中Col1α1和MMP-9的转录水平。发现抗 RAGE 可在体内和体外抑制肝星状细胞增殖。因此，抗RAGE可以保护大鼠肝脏免受BDL诱导的损伤。
Cholestasis leads to acute hepatic injury, fibrosis/cirrhosis, inflammation, and duct proliferation. We investigated whether blocking receptor of advanced glycation end-products (RAGE) with polyclonal anti-RAGE antibodies (anti-RAGE) could regulate acute liver injury and fibrosis in a rat bile duct ligation (BDL) model. Male Wister rats received 0.5 mg/kg rabbit anti-RAGE or an equal amount of rabbit IgG by subcutaneous injection twice a week after BDL. Samples of liver tissue and peripheral blood were collected at 14 days after BDL. Serum biochemistry and histology were used to analyze the degree of liver injury. Quantitative real-time PCR (qPCR) and immunohistochemical staining were used to further analyze liver injury. Anti-RAGE improved the gross appearance of the liver and the rat survival rate. Liver tissue histology and relevant serum biochemistry indicated that anti-RAGE attenuated liver necrosis, inflammation, liver fibrosis, and duct proliferation in the BDL model. qPCR and western blotting showed significant reductions in interleukin-1β expression levels in the liver by treatment with anti-RAGE. Anti-RAGE also significantly reduced the mRNA levels of α1(1) collagen (Col1α1) and cholesterol 7α-hydroxylase, and the ratio of tissue inhibitor of matrix metalloproteinase-1 to matrix metalloproteinases (MMPs) in the liver. In addition, anti-RAGE regulated the transcriptional level of Col1α1 and MMP-9 in transforming growth factor-β-induced activated LX-2 cellsin vitro. Anti-RAGE was found to inhibit hepatic stellate cell proliferationin vivoandin vitro. Therefore, anti-RAGE can protect the liver from injury induced by BDL in rats.
影响因子：
6.4
作者：
Bandyopadhyay, Sarmistha;Friedman, Robin C.;McCaffrey, Anton P.
通讯作者：
McCaffrey, Anton P.
DOI：
--
发表时间：
1995-02
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
R. Botla;J. Spivey;H. Aguilar;S. Bronk;G. Gores
通讯作者：
R. Botla;J. Spivey;H. Aguilar;S. Bronk;G. Gores
DOI：
10.1152/ajpgi.00151.2013
发表时间：
2013-12-01
影响因子：
4.5
作者：
Seo, Yeon S.;Kwon, Jung H.;Shah, Vijay H.
通讯作者：
Shah, Vijay H.