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KIOM-79 通过抑制 NF-κB 活化来保护AGE 诱导的视网膜周细胞凋亡,在体内外研究中均得到验证。

KIOM-79 protects AGE-induced retinal pericyte apoptosis via inhibition of NF-kappaB activation in vitro and in vivo.

机构信息

Traditional Korean Medicine (TKM) Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea.

出版信息

PLoS One. 2012;7(8):e43591. doi: 10.1371/journal.pone.0043591. Epub 2012 Aug 20.

Abstract

KIOM-79 is an herbal mixture of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix. In the present study, we determined the efficacy and possible mechanism of KIOM-79 on the advanced glycation end product (AGE)-modified bovine serum albumin (BSA)-induced apoptosis of cultured bovine retinal pericytes and rat retinal pericytes in Zucker diabetic fatty (ZDF) rats. Seven-week-old male ZDF rats were treated with KIOM-79 (50 mg/kg body weight) once a day orally for 13 weeks. KIOM-79 significantly inhibited pericyte apoptosis which were induced by the AGE-BSA treatment. The KIOM-79 treatment markedly suppressed the activation of nuclear factor-kappaB (NF-κB) through the inhibition of inhibitory κB kinase complex. In addition, the oral administration of KIOM-79 inhibited the changes in retinal vasculature (vascular hyperpermeability, acellular capillary). KIOM-79 strongly inhibited pericyte apoptosis, NF-κB activation and the expression of pro-apoptotic Bax and tumor necrosis factor-α. Our results suggest that KIOM-79 may exert inhibitory effects on AGE-induced pericyte apoptosis by blocking NF-κB activation, thereby ameliorating retinal microvascular dysfunction.

摘要

KIOM-79 是一种由干燥葛根、姜黄、甘草和大戟组成的草药混合物。在本研究中,我们测定了 KIOM-79 对晚期糖基化终产物(AGE)修饰牛血清白蛋白(BSA)诱导的培养牛视网膜周细胞和 Zucker 糖尿病肥胖(ZDF)大鼠视网膜周细胞凋亡的疗效及其可能的机制。7 周龄雄性 ZDF 大鼠每天口服 KIOM-79(50mg/kg 体重),共 13 周。KIOM-79 显著抑制了 AGE-BSA 处理诱导的周细胞凋亡。KIOM-79 通过抑制抑制κB 激酶复合物,显著抑制核因子-κB(NF-κB)的激活。此外,KIOM-79 的口服给药抑制了视网膜血管(血管高通透性、无细胞毛细血管)的变化。KIOM-79 强烈抑制周细胞凋亡、NF-κB 激活以及促凋亡 Bax 和肿瘤坏死因子-α的表达。我们的结果表明,KIOM-79 通过阻断 NF-κB 激活可能对 AGE 诱导的周细胞凋亡发挥抑制作用,从而改善视网膜微血管功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1bc/3423361/13ab29cb8427/pone.0043591.g001.jpg

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