文献类型：期刊文献

中文题名：萆薢分清颗粒对阿霉素肾病大鼠足细胞podocalyxin、α-actinin-4的影响

英文题名：Effect of Bixie Fenqing granules on podocalyxin andα-actinin-4 in podocytes in rats with adriamycin-induced nephropathy

作者：马雪莉[1];魏锦慧[1];马鸿斌[1]

第一作者：马雪莉

机构：[1]甘肃中医药大学附属医院,兰州730000

第一机构：甘肃中医药大学第二附属医院

年份：2022

卷号：32

期号：12

起止页码：49

中文期刊名：中国比较医学杂志

外文期刊名：Chinese Journal of Comparative Medicine

收录：CSTPCD;;北大核心:【北大核心2020】；

基金：甘肃中医药大学附属医院院内创新基金项目(gzfy-2018-02,gzfy-2020-12)。

语种：中文

中文关键词：阿霉素肾病大鼠;萆薢分清颗粒;足细胞;podocalyxin;α-actinin-4

外文关键词：adriamycin nephropathy rats;Bixie Fenqing granules;podocyte;podocalyxin;α-actinin-4

摘要：目的探讨萆薢分清颗粒对阿霉素肾病大鼠蛋白尿及肾组织足细胞足糖萼蛋白(podocalyxin)、α-辅肌动蛋白-4(α-actinin-4)的影响。方法将60只SPF级SD大鼠,随机分为空白组12只和造模组48只,造模组大鼠采用分两次尾静脉注射的方法建立阿霉素肾病大鼠模型。造模成功后随机分为模型组、萆薢分清颗粒(6.56 mL/kg)组(中药组)、泼尼松组(6.3 mL/kg)、萆薢分清颗粒+泼尼松组(结合组)进行灌胃,空白组及模型组予以同等量生理盐水灌胃,每日1次,连续灌胃4周。给药结束后检测大鼠24 h尿蛋白定量(24 h-UTP)、血清总胆固醇(TC),白蛋白(ALB)水平;采用苏木素-伊红(HE)染色、马松(Masson)染色观察肾组织病理形态学变化,应用免疫组化法(IHC)及蛋白免疫印迹法(Western blot)检测大鼠肾组织中足细胞相关蛋白podocalyxin、α-actinin-4表达水平。结果空白组比较,模型组大鼠24 h-UTP、血清中TC显著升高(P<0.05);ALB显著降低(P<0.05);肾小球可见局灶节段性瘢痕形成,系膜细胞及系膜基质增生,肾小管空泡变性,管腔内可见蛋白管型,间质纤维细胞增生伴炎性细胞浸润;podocalyxin阳性表达明显减弱,α-actinin-4呈强阳性表达(P<0.05);podocalyxin蛋白表达量显著下降(P<0.05),α-actinin-4蛋白表达量显著升高(P<0.05)。与模型组比较,各治疗组24 h-UTP,血清TC水平均有不同程度的下降,ALB升高(P<0.05);肾小球及小管间质病变较轻,少许肾间质水肿、纤维化,伴有少量炎性细胞浸润;podocalyxin阳性表达增强,α-actinin-4阳性表达减弱(P<0.05);podocalyxin蛋白表达量显著升高(P<0.05),α-actinin-4蛋白表达量显著降低(P<0.05)。结论萆薢分清颗粒可通过上调podocalyxin、下调α-actinin-4表达水平,从多靶点修复受损的足细胞,减少尿蛋白排泄量,保护肾。
Objective To explore the effects of Bixie Fenqing granules on proteinuria and podocyte podocalyxin andα-actinin-4 expression in renal tissues of rats with adriamycin-induced nephropathy.Methods Sixty specific-pathogen-free SD rats were divided randomly into a blank group(n=12)and model group(n=48).A rat model of adriamycin-induced nephropathy was established by two injections of adriamycin into the tail vein.After successful establishment of the model,the rats were divided randomly into a model group,Bixie Fenqing granules group(6.56 mL/kg)(Chinese medicine group),prednisone group(6.3 mL/kg),and Bixie Fenqing granules+prednisone group(combination group).Treatments were administered once a day for 4 weeks and the blank and model groups were given the same amount of normal saline.Levels of 24 h urinary protein(24 h-UTP),serum total cholesterol(TC),and albumin were measured and pathomorphological changes in renal tissue were observed by hematoxylin and eosin and Masson staining.Expression levels of the podocyte-associated protein podocalyxin andα-actinin-4 in rat kidney tissues were detected by immunohistochemistry and Western blot.Results Serum TC and 24 h-UTP were significantly increased and albumin was significantly decreased in the model group compared with the blank group(P<0.05).Renal tissues in model rats showed focal segmental scar formation,proliferation of mesangial cells and mesangial matrix,vacuolar degeneration of renal tubules and protein tubules in the lumen,and interstitial fibrous cell proliferation with inflammatory cell infiltration.Podocalyxin expression was significantly decreased andα-actinin-4 expression was increased(P<0.05)in the model group compared with the control group.Conversely,compared with the model group,24 h-UTP and serum TC were decreased and albumin was increased to different degrees in each treatment group(P<0.05),glomerular and tubulointerstitial lesions were mild,with little renal interstitial edema and fibrosis,accompanied by a small amount of inflammatory cell infiltration,and podocalyxin expression was increased andα-actinin-4 expression was decreased(P<0.05).Conclusions Bixie Fenqing granules can repair damaged podocytes via multiple targets,reduce UTP excretion,and protect the kidney by up-regulating podocalyxin and down-regulating the expression ofα-actinin-4.