摘要
目的 利用网络药理学的方法预测丹参(SM)治疗糖尿病肾病(DKD)的作用靶点并通过动物实验进行验证。方法 根据中药系统药理学分析平台(TCMSP)筛选SM的有效成分。分别收集SM各种有效成分的作用靶点和DKD的作用靶点,取交集后的靶点即为SM治疗DKD的潜在作用靶点。将这些作用靶点导入DAVID数据库进行GO富集分析和KEGG通路富集分析。通过腹腔注射链脲佐菌素(STZ)的方法构建DKD大鼠模型,并将造模成功的DKD大鼠分为3组:模型组(n=9)、丹参治疗组(n=9)和缬沙坦治疗组(n=8),另取10只正常大鼠作为对照组。各组大鼠进行相应处理8周后处死,收集血清、24 h尿液和肾脏组织。检测空腹血糖(FBG)、尿素氮(BUN)、肌酐(Scr)、24 h尿蛋白水平。肾组织经包埋后切片行苏木精-伊红染色、PAS染色。Western blot法检测肾组织中P-PI3K、P-AKT、PI3K和AKT表达水平。结果 网络药理学研究结果表明,SM中含有65种有效成分。这些有效成分预测到170个靶点,而DKD疾病预测到1 389个靶点,取交集后得到SM治疗DKD的作用靶点83个。KEGG通路富集分析显示,PI3K-AKT等信号通路可能在其中发挥关键作用。动物实验结果显示,与模型组相比,丹参治疗组BUN、24 h尿蛋白和Scr水平显著降低,差异有统计学意义(P<0.01)。肾脏组织病理切片显示,DKD大鼠肾脏组织存在明显损伤伴有大量胶原沉积,经丹参注射液治疗后有所减轻。Western blot结果显示,与模型组相比,丹参治疗组肾脏组织P-PI3K和P-AKT的表达显著增加,差异有统计学意义(P<0.01)。结论 网络药理学与动物实验结果均提示,丹参注射液可有效治疗DKD,其作用机制可能与PI3K-AKT信号通路有关。
Objective To predict the functioning targets of Salvia miltiorrhiza(SM) and diabetic kidney disease(DKD) by network pharmacology and validate using a DKD rat model.Methods Active ingredients present in SM were screened out using the TCMSP database. The functioning targets of each active ingredient and DKD were collected and their intersections were considered the potential functional targets of SM for DKD treatment. The potential functional targets were imported into DAVID database for GO enrichment analysis and KEGG enrichment analysis. Furthermore, a DKD rat model was constructed through intraperitoneal injection of streptozocin(STZ). The DKD rats were divided into three groups: a model group(n=9), a SM treatment group(n=9) and a valsartan treatment group(n=8). Meanwhile, another ten healthy rats were selected as a control group. Rats in each group were subjected to corresponding treatment for eight weeks. Then, the animals were scarified and their serum, 24 h urine and kidney tissues were collected. The levels of fasting blood glucose(FBG), blood urea nitrogen(BUN), serum creatinine(Scr), and 24-h urinary protein were determined. Kidney tissues were embedded and sliced, before hematoxylin-eosin staining and PAS staining. The expression of P-PI3K, P-AKT, PI3K and AKT in kidney tissues was determined by Western blot.Results According to network-based pharmacological analysis, there were 65 active ingredients in SM. These active ingredients had 170 putative gene targets, while 1,389 putative gene targets were screened for DKD. There were 83 intersections among the putative targets for DKD treatment using SM. KEGG pathway enrichment analysis suggested the potentially important role of the PI3K-AKT signaling pathway. According to animal experiment results, compared with the model group, the SM treatment group showed remarkable decreases in BUN, 24-h urinary protein and Scr levels(P<0.01). Furthermore, obvious damage was seen in DKD rats, with large amounts of accumulated collagen, which were relieved after injectio
作者
王豪
孙依敏
马琴
韩佳林
李正泰
周瑶
WANG Hao;SUN Yimin;MA Qin;HAN Jialin;LI Zhengtai;ZHOU Yao(The First School of Clinical Medicine,Xuzhou Medical University,Xuzhou,Jiangsu 221004,China;Department of Pathophysiology,Xuzhou Medical University)
出处
《徐州医科大学学报》
CAS
2022年第12期859-865,共7页
Journal of Xuzhou Medical University
基金
国家自然科学基金青年项目(82104624)
江苏省高等学校大学生创新创业训练计划(202210313009Z)。
关键词
糖尿病肾病
丹参
网络药理学
diabetic kidney disease
Salvia miltiorrhiza
network pharmacology
