益气活血解毒中药调控VEGF通路抑制单侧输尿管结扎大鼠对侧肾脏淋巴管生成的研究  

Yiqi Huoxue Jiedu decoction inhibits lymphangiogenesis in contralateral kidney of UUO rats via VEGF pathway

作　　者：高晓萌 赵绮悦 刘子骞 刘令今 陈格格 郝娟 王香婷 许庆友 GAO Xiao-meng;ZHAO Qi-yue;LIU Zi-qian;LIU Ling-jin;CHEN Ge-ge;HAO Juan;WANG Xiang-ting;XU Qing-you(Graduate School,Hebei University of Chinese Medicine;Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns;College of Integrated Chinese and Western Medicine,Hebei University of Chinese Medicine,Shijiazhuang 050091,China)

机构地区：[1]河北中医学院研究生学院 [2]河北省中西医结合肝肾病证研究重点实验室 [3]河北中医学院中西医结合学院,石家庄050091

出　　处：《天然产物研究与开发》2021年第9期1539-1547,共9页Natural Product Research and Development

基　　金：国家自然科学基金(81473652,81873251);河北中医学院科技能力提升项目(3010105231022)。

摘　　要：观察益气活血解毒中药对单侧输尿管结扎大鼠对侧肾脏淋巴管新生的影响及作用机制。将40只Wistar大鼠随机分为假手术组(Sham)、单侧输尿管结扎组(UUO)、依普利酮治疗组(EPL)和中药治疗组(TCM),每组各10只。除假手术组外,其余大鼠结扎单侧输尿管(UUO)复制肾间质纤维化动物模型。术后10天摘取大鼠对侧肾脏,HE、Masson检测肾脏病理,免疫荧光及组化方法检测NCC、VEGF-C、VEGFR-3、LYVE-1、PDPN、α-SMA、Vimentin的表达。Western blot检测肾组织NCC、VEGF-C、VEGFR-3和α-SMA的蛋白表达。病理结果显示UUO大鼠对侧肾脏小管间质炎性细胞浸润增多并伴局灶胶原纤维沉积;NCC及VEGF-C表达增强;淋巴管生成标志物LYVE-1、VEGFR-3、PDPN表达增强并与肌成纤维细胞标志物α-SMA、Vimentin呈共表达;益气活血解毒中药可抑制NCC表达、淋巴管生成及表型转化。以上结果说明益气活血解毒中药可调控VEGF通路,抑制梗阻性肾病对侧肾脏淋巴管生成及表型转化,减缓肾脏纤维化进展。To observe the effect of Yiqi Huoxue Jiedu decoction on lymphangiogenesis in the contralateral kidney of UUO rats.Forty Wistar rats were randomly divided into sham operation group(Sham),unilateral ureteral obstruction(UUO)group,eplerenone treated group(EPL)and Chinese decoction treated group(TCM)(n=10).Except for the sham operation group,the other rats were established by unilateral ureteral ligation.Ten days after the operation,contralateral kidney of the UUO rat have harvested.The histopathology was observed by HE and Masson staining.The expression of NCC,VEGF-C,VEGFR-3,LYVE-1,PDPN,α-SMA and Vimentin were detected with immunohistochemistry or immunofluorescence.The expression of NCC,VEGF-C,VEGFR-3 andα-SMA in renal tissue have detected with Western blot.The renal histopathological change showed that the infiltrated inflammatory cells increased in tubular interstitium in UUO rats and accompanied with focal collagen deposition.Overexpression of NCC and VEGF-C showed in UUO rats.The expression of lymphangiogenesis markers(LYVE-1,VEGFR-3 and PDPN)was enhanced and co-expressed with the myofibroblast markers(α-SMA and Vimentin);Yiqi Huoxue Jiedu decoction can inhibit the expression of NCC,lymphangiogenesis and phenotypic transformation.These results suggest Yiqi Huoxue Jiedu decoction could inhibit the lymphangiogenesis and phenotypic transformation in the contralateral kidney of UUO rats,and prolong the progression of renal fibrosis by regulating VEGF pathway.

关 键 词：益气活血解毒中药 VEGF-C 淋巴管新生 LYVE-1 单侧输尿管结扎 

分 类 号：R285[医药卫生—中药学]