中国组织工程研究2018,Vol.22Issue(8):1247-1254,8.DOI:10.3969/j.issn.2095-4344.0144
姜黄素抗肝窦毛细血管化作用及机制
Effect of curcumin against capillarization of hepatic sinusoids and its mechanism
摘要
Abstract
BACKGROUND: Capillarization of hepatic sinusoids is an inevitable part in liver fibrosis and cirrhosis, and is a characteristic lesion inducing portal hypertension. However, curcumin effects on the capillarization of hepatic sinusoids and the underlying mechanism remain unclear. OBJECTIVE: To observe the effect of curcumin (a natural polyphenolic compound derived from the rhizome of Curcuma longa)on the microstructure and secretion of hepatic sinusoidal endothelial cells(HSECs),and to further explore its intervention on sinusoidal capillarization and pharmacological action mechanism of anti-liver fibrosis and target sites. METHODS: The rat HSECs were cultured and divided into seven groups: blank control group received no intervention and cells in the other groups were activated by leptin, followed by treatment with nothing (model group), high-, medium- and low-dose of curcumin, colchicine and salvia miltiorrhiza phenolic acid B, respectively, for 48 hours. RESULTS AND CONCLUSION: Under scanning and transmission electron microscopes, with the increasing activation of leptin, the number of fenestrae in HSECs was increased and the aperture was decreased. Curcumin could increase and enlarge narrowed or disappeared fenestrae caused by leptin, attenuated the thickness and scope of extracellular basement membrane, and reduced the degree of capillarization of hepatic sinusoids in a dose-dependent manner. Real-time PCR and ELISA results showed that after activation of leptin, mRNA and protein expression levels of endothelin-1 and vascular endothelial growth factor in HSECs were significantly increased compared with the blank control group (P < 0.05), while the expressions showed a significant decrease after treatment with curcumin in a dose-dependent manner (P < 0.05). There was also a gradient reduction in the protein expression of endothelin-1 and vascular endothelial growth factor in HSECs treated with curcumin. Moreover, all above mRNA and protein expression levels in the high-dose curcumin group were significantly lower than those in the colchicine and salvia miltiorrhiza phenolic acid B groups. In summary, curcumin can significantly alleviate the sinusoidal capillarization, and thus delay the development of liver fibrosis, probably by down-regulating the expression levels of endothelin-1 and vascular endothelial growth factor.关键词
姜黄素/肝窦内皮细胞/组织工程/肝窦毛细血管化/窗孔/基底膜/分泌功能/瘦素/内皮素1/血管内皮生长因子/抗纤维化分类
医药卫生引用本文复制引用
段雪琳,彭岳,赵铁建,韦燕飞,黎桂玉..姜黄素抗肝窦毛细血管化作用及机制[J].中国组织工程研究,2018,22(8):1247-1254,8.基金项目
国家自然科学基金项目(81403189, 81460628,81660705,81560690) (81403189, 81460628,81660705,81560690)
广西教育厅高教科研项目(YB2014182)the National Natural Science Foundation of China, No. 81403189, 81460628, 81660705 and 81560690 (YB2014182)
Scientific Research Project of Universities of Education Department of Guangxi Zhuang Autonomous Region, No. YB2014182 ()