毛蕊花糖苷改善单侧输尿管梗阻模型大鼠肾纤维化  

Acteoside improves renal fibrosis in rats with unilateral ureteral obstruction

作　　者：林鑫[1,2] 谢莹 江栎丞[4] 董蓉 余佳丽 袁静[1,5] 查艳 Lin Xin;Xie Ying;Jiang Licheng;Dong Rong;Yu Jiali;Yuan Jing;Zha Yan(Department of Nephrology,Guizhou Provincial People's Hospital,Guiyang 550002,China;Guizhou Provincial Institute of Nephritic and Urinary Disease,Guiyang 550002,China;Medical College of Guizhou University Internal Medicine Department,Guiyang 550002,China;Zunyi Medical University Graduate School,Zunyi 563000,China;Key Laboratory of Diagnosis and Treatment of Pulmonary Immune Diseases,National Health Commission,Guiyang 550002,China)

机构地区：[1]贵州省人民医院肾内科,贵阳550002 [2]贵州省肾脏泌尿疾病研究所,贵阳550002 [3]贵州大学医学院内科学教研室,贵阳550002 [4]遵义医科大学研究生院,遵义563000 [5]国家卫生健康委员会肺脏免疫性疾病诊治重点实验室,贵阳550002

出　　处：《中华肾脏病杂志》2023年第10期778-782,共5页Chinese Journal of Nephrology

基　　金：贵州省卫生健康委员会科学技术基金(GZWKJ〔2021〕135);贵州省科技支撑计划项目(黔科合支撑〔2019〕2801号);贵州省肾脏病临床医学研究中心(黔科合平台人才〔2020〕2201号);贵州省高层次创新人才项目(黔科合平台人才〔2018〕5636);中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2019PT320003)。

摘　　要：该研究探讨毛蕊花糖苷对单侧输尿管梗阻模型大鼠肾纤维化的作用。采用随机数字表法将24只成年健康雄性SD大鼠随机分为假手术(CON)组、单侧输尿管梗阻(UUO)组、UUO+毛蕊花糖苷(ACT)组和UUO+贝那普利(BZ)组,采用单侧输尿管结扎术建立肾纤维化动物模型。HE染色和Masson染色观察各组大鼠肾组织病理改变。免疫组化法检测肾组织Ⅲ型胶原蛋白(CollagenⅢ)、热休克蛋白(HSP)-47、结缔组织生长因子(CTGF)、α平滑肌肌动蛋白(α-SMA)、β联蛋白(β-catenin)、B细胞淋巴瘤因子2(Bcl-2)和半胱氨酸蛋白酶3(Caspase-3)蛋白的表达。Western印迹法检测肾组织葡萄糖调节蛋白(GRP)78蛋白表达。结果显示,与CON组比较,UUO组大鼠肾小管扩张,肾间质胶原纤维沉积显著增加;UUO+ACT组和UUO+BZ组大鼠肾小管扩张和间质胶原纤维沉积程度较UUO组显著减轻,但仍明显重于CON组。与CON组比较,UUO组大鼠肾组织CTGF、α-SMA、CollagenⅢ、HSP-47、β-catenin及GRP78蛋白表达量均显著较高,Bcl-2蛋白表达量显著较低(均P<0.05);与UUO组比较,UUO+ACT组和UUO+BZ组大鼠肾组织Bcl-2蛋白表达量均显著较高,而其他蛋白表达量均显著较低(均P<0.05)。该研究表明,毛蕊花糖苷可通过下调CTGF、α-SMA、CollagenⅢ、HSP-47、β-catenin及GRP78表达,上调Bcl-2表达,从而发挥改善肾纤维化的作用。The study explored the effect of acteoside on renal fibrosis in rats with unilateral ureteral obstruction.Twenty-four healthy adult male SD rats were randomly divided into sham(CON)group,unilateral ureteral obstruction(UUO)group,UUO+acteoside(ACT)group,UUO+benazepril(BZ)group by random number table method.The animal model of renal fibrosis was established by unilateral ureteral ligation.The pathological changes of renal tissues in each group of rats were observed by HE staining and Masson staining.Immunohistochemical method was used to detect the protein expression levels of collagenⅢ,heat shock protein(HSP)-47,connective tissue growth factor(CTGF),α-smooth muscle actin(α-SMA),β-catenin,Bcl-2,and caspase-3.Western blotting was used to detect the protein expression of glucose-regulated protein 78(GRP78)in renal tissue.Compared with CON group,UUO group had renal tubular dilation and significantly increased interstitial collagen fiber deposition;The degree of renal tubular dilation and interstitial collagen fibers in UUO+ACT group and UUO+BZ group were significantly reduced compared to UUO group,but still significantly heavier than CON group.Compared with CON group,the protein expression levels of collagenⅢ,HSP-47,CTGF,α-SMA,β-catenin and GRP78 in renal tissues of UUO group were significantly higher,while the protein expression level of Bcl-2 was significantly lower(all P<0.05).In comparison with UUO group,the expression levels of Bcl-2 in UUO+ACT group and UUO+BZ group were significantly higher,while the expression levels of other proteins were all significantly lower(all P<0.05).The study shows that acteoside may improve renal fibrosis by decreasing the expression levels of collagenⅢ,HSP-47,CTGF,α-SMA,β-catenin and GRP78,and upregulating the expression level of Bcl-2 in renal tissues.

关 键 词：麦角甾苷 纤维化 输尿管梗阻 肌成纤维细胞 细胞外基质 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]