基于地黄生、熟的肾气丸治疗糖尿病肾病模型小鼠药效差异研究  

Study on the difference in efficacy of Shenqi Pill based on raw and ripened Dihuang in treating a mouse model with diabetic kidney disease

作　　者：张琳 王献 张文龙 裴海鹏 任天爱 谢毅强[1] 李凯 ZHANG Lin;WANG Xian;ZHANG Wenlong;PEI Haipeng;REN Tianai;XIE Yiqiang;LI Kai(Hainan Medical University,Haikou 571199,China)

机构地区：[1]海南医学院,海南海口571199

出　　处：《海南医学院学报》2024年第15期1121-1128,共8页Journal of Hainan Medical University

基　　金：国家自然科学基金资助项目(82160897、82205087);海南省“南海新星”教育平台资助项目(JYNHXX2023-16G)。

摘　　要：目的:探讨地黄生、熟的肾气丸对DKD模型小鼠的药效差异及可能的相关机制。方法:选取8只SPF级6~8周龄雄性db/m小鼠作为正常对照组(Control组),另选取24只SPF级6~8周龄雄性db/db小鼠按测定血糖随机分组为:模型对照组(Model组)、肾气丸生地黄组(S-L组)与肾气丸熟地黄组(S-R组),每组db/db小鼠8只。造模成功后,S-L组与S-R组每日分别灌服含有生、熟地黄的肾气丸水煎液(10.4 g/kg),正常组与模型组每日灌服等量生理盐水,连续56 d,检测二者对DKD模型小鼠末次给药24 h后空腹血糖、24 h尿蛋白定量(UP)、微量白蛋白(mAIB)、尿肌酐(Ucr)含量;总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、肌酐(SCr)、尿素氮(BUN)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆红素(TBIL)含量;HE染色观察肾脏组织病理形态学变化;Western blot法检测各组PI3K、Akt的蛋白含量。结果:与C组相比,Mo组小鼠空腹血糖、GSP、mAIB、Scr、UP、Ucr、TC、TG、LDL-C、ALT、AST、TBIL均增高,HDL-C、Ucr降低,HE染色显示肾小球系膜增生、肾小球系膜细胞增多、系膜基质沉积明显,PI3K、Akt蛋白的表达下调。与Mo组比较,S-L组与S-R组在生化指标上较Mo型组均有好转,HE染色显示肾小球病理损伤有所改善,并能上调PI3K、Akt的蛋白表达,差异有统计学意义(P<0.05);但治疗后两组对比,S-R组BUN、SCr、UP含量明显更低(P<0.05),AST低于S-L组差异明显(P<0.05)。结论:肾气丸中生、熟地黄均可改善DKD引起的肾功能损伤,而肾气丸熟地黄组在治疗DKD小鼠时药效更显著,其机制可能与上调肾组织中PI3K、Akt的表达水平有关。Objective:To investigate the differences in efficacy and possible related mechanisms between Shenqi Pill with raw and ripened Dihuang in diabetic kidney disease(DKD) mice.Methods:Eight male db/m mice of SPF grade 6-8 weeks old were selected as the normal control group(Control group),and another 24 male db/db mice of SPF grade 6-8 weeks old were selected and randomly grouped according to the measurement of blood glucose as follows:the model control group(Model group),the Shenqi Pill raw Dihuang group(S-L group) and Shenqi Pill ripened Dihuang group(S-R group),with 8 db/db mice in each group.After successful modeling,the S-L group and the S-R group were dosed daily with a decoction of Shenqi Pill containing raw and cooked Dihuang(10.4 g/kg),and the normal group and the model group were dosed daily with an equal amount of saline for 56 d.The effects of these two drugs on the levels of fasting blood glucose,24-h urinary protein(UP),microalbumin(mAIB),urinary creatinine(Ucr),total cholesterol(TC),total triglyceride(TG),low-density lipoprotein(LDL-C),high-density lipoprotein(HDL-C),creatinine(SCr),blood urea nitrogen(BUN),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and bilirubin(TBIL) were measured HE staining was conductedto observe the pathomorphologic changes of renal tissues,and Western blot assay to detect protein content of PI3K and Akt in each group.Results:Compared with the control group C,fasting blood glucose,GSP,mAIB,Scr,UP,Ucr,TC,TG,LDL-C,ALT,AST,and TBIL were increased and HDL-C and Ucr were decreased in mice in the model Mo group,and H&E staining showed that glomerular thylakoid membrane hyperplasia,glomerular thylakoid cell increase,thylakoid matrix deposition were obvious,and the expressions of PI3K and Akt proteins were down-regulated.Compared with the model group,both the S-L group and the S-R group showed an improvement in biochemical indexes,and H& E staining showed that glomerular pathological injury was improved,and the expression of PI3K and Akt proteins were significantly up-re

关 键 词：生地黄 熟地黄 肾气丸 糖尿病肾病 药效研究 

分 类 号：R285.5[医药卫生—中药学]