天阳丸对糖尿病肾病小鼠肾功能及足细胞损伤标志蛋白的影响  

Tianyang Pill on renal function and podocyte injury marker protein in diabetic kidney disease mice

作　　者：韩东卫 高远 张维君 高红 陶明源 逯柯儿 刘成 HAN Dongwei;GAO Yuan;ZHANG Weijun;GAO Hong;TAO Mingyuan;LU Keer;LIU Cheng(Basic Medical College of Heilongjiang University of Chinese Medicine,Harbin Heilongjiang,150040;Key Laboratory of Basic and Applied Research of North Medicine,Harbin Heilongjiang,150040;School of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang Guizhou,550025)

机构地区：[1]黑龙江中医药大学基础医学院,黑龙江哈尔滨150040 [2]北药基础与应用研究重点实验室,黑龙江哈尔滨150040 [3]贵州中医药大学药学院,贵州贵阳550025

出　　处：《广西中医药》2023年第4期60-64,70,共6页Guangxi Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(编号:81904090);黑龙江中医药大学“优秀创新人才支持计划”(校政发[2018]19号)。

摘　　要：目的:探究天阳丸对链脲佐菌素(STZ)诱导的糖尿病肾病(DKD)小鼠肾功能的保护作用。方法:将小鼠随机分为空白对照组、模型组、天阳丸组、二甲双胍组。小鼠采用腹腔注射STZ建立DKD模型,模型复制成功后给药干预,天阳丸组按照12.5 g/(kg·d)剂量灌胃,二甲双胍组按照0.2 g/(kg·d)灌胃,空白对照组和模型组灌胃等体积生理盐水,各组灌胃体积均为20 ml/kg,连续给药3周。末次给药后,分别收集各组小鼠血清、尿液样本,尾静脉取血测血糖,称定体质量和双肾湿质量,检测血清总胆固醇(TC)、甘油三酯(TG)、肌酐(Crea)、尿素(Urea)与白蛋白(ALB)的水平,以ELISA法测定血清晚期糖基化终末期产物(AGEs)、血清足细胞损伤标志蛋白(PCX)、足细胞裂孔膜蛋白(Nephrin)的水平,以qRT-PCR法检测肾组织PCX mRNA和Nephrin mRNA表达水平,采用HE、PAS与Masson染色法观察肾组织病理学变化。结果:与空白对照组比较,模型组小鼠24 h尿蛋白(24 h-UP)、血糖、肾脏系数及血清Crea、Urea、ALB、AGEs水平显著升高(P<0.05);与模型组比较,天阳丸组小鼠24 h-UP、肾脏系数及血清Crea、Urea、ALB水平显著降低(P<0.05),血清PCX、Nephrin蛋白与肾组织PCX mRNA、Nephrin mRNA水平显著升高(P<0.05)。结论:天阳丸能够显著改善DKD小鼠肾功能,对24 h-UP、肾脏系数、血清Crea、Urea、ALB、AGEs以及足细胞损伤标志蛋白PCX、Nephrin水平均有明显改善作用。Objective:To investigate the protective effect of Tianyang Pill on renal function in streptozotocin(STZ)-induced diabetic kidney disease(DKD)mice.Methods:The mice were randomly divided into four groups as blank control group,model group,Tianyang Pill group and metformin group.The DKD model was established by intra⁃peritoneal injection of STZ in mice.After successful replication of the model,Tianyang Pill was administered by gastric gavage at a dose of 12.5 g/(kg·d),metformin was administered by gastric gavage at a dose of 0.2 g/(kg·d),and the blank control group and the model group were given an equal volume of normal saline.The gastric gavage volume of each group was 20 ml/kg.The gastric gavage was conducted for 3 weeks in each group.After the last administration,serum and urine samples were collected from the mice.The levels of serum total cholesterol(TC),triglyceride(TG),creatinine(Crea),urea(Urea),and albumin(ALB)were measured.The levels of serum advanced glycation end products(AGEs),serum podocyte injury marker protein(PCX),and podocyte pore membrane protein(Nephrin)were measured by ELISA.The expression levels of PCX mRNA and Nephrin mRNA in renal tissue were detected by qRT-PCR.The pathological changes of renal tissue were observed by HE,PAS,and Masson staining.Results:Compared with the blank control group,the levels of 24 h urine protein(24 h-UP),blood glucose,kidney coefficient,serum Crea,Urea,ALB,and AGEs in the model group were significantly increased(P<0.05).Compared with the model group,the 24 h-UP,kidney coeffi⁃cient,serum Crea,Urea,and ALB levels in the Tianyang Pill group were significantly decreased(P<0.05),and the se⁃rum PCX and Nephrin protein and renal tissue PCX and Nephrin mRNA levels were significantly increased(P<0.05).Conclusion:Tianyang Pill can significantly improve the renal function of DKD mice,and significantly im⁃prove 24 h-UP,kidney coefficient,serum Crea,Urea,ALB,AGEs,and podocyte injury marker proteins PCX and Neph⁃rin in mice.

关 键 词：天阳丸 糖尿病肾病 肾功能 PCX蛋白 Nephrin蛋白 

分 类 号：R285.5[医药卫生—中药学]