图1 

Figure 1 

图2 

注：A，葛根芩连汤（GQD）与糖尿病心脏病（DHD）的交集靶点图；B，基于STRING数据库构建的蛋白质-蛋白质相互作用（PPI）网络图；C，交集靶点的基因本体（GO）生物过程富集图；D，交集靶点的GO分子功能富集图；E，交集靶点的GO细胞组分富集图；F，交集靶点的京都基因和基因组数据库（KEGG）通路富集图。STAT3，信号转导与转录激活因子3；TNF，肿瘤坏死因子；SRC，非受体型酪氨酸蛋白激酶；Akt，蛋白激酶B；TP53，肿瘤蛋白p53；EGFR，表皮生长因子受体；MAPK，丝裂原激活的蛋白激酶；EP300，腺病毒E1A结合蛋白；JUN，Jun激酶；AGE，晚期糖基化终末产物；IL-17，白细胞介素-17；FoxO，叉头框蛋白O。

Figure 2 

Note： A， Intersection target map of Gegen Qinlian decoction （GQD） and diabetic heart disease （DHD）； B， Protein-protein interaction （PPI） network map constructed using the STRING database； C， Gene ontology （GO） biological process enrichment map of intersection targets； D， GO molecular function enrichment map of intersection targets； E， GO cellular component enrichment map of intersection targets； F， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment map of intersection targets. STAT3， signal transducer and activator of transcription 3； TNF， tumor necrosis factor； SRC， non-receptor tyrosine protein kinase； Akt， protein kinase B； TP53， tumor protein p53； EGFR， epidermal growth factor receptor； MAPK， mitogen-activated protein kinase； EP300， adenovirus E1A-binding protein； JUN， Jun kinase； AGE， advanced glycation end products； IL-17， interleukin-17； FoxO， forkhead box protein O.

图3 

注：A～E，ELISA法检测各组小鼠血清中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、CXC趋化因子配体2（CXCL2）、高迁移率族蛋白B1（HMGB1）、单核细胞趋化蛋白-1（MCP-1）含量的变化（n=6）。造模组（模型对照组、GQD高剂量组）小鼠以60%高脂饲料+5%葡萄糖水喂养4周，禁食12 h后腹腔注射100 mg/kg STZ（使用柠檬酸盐缓冲液配制）诱导2型糖尿病动物模型；正常对照组给予普通饲料和饮用水，同期禁食12 h后腹腔注射等体积柠檬酸盐缓冲液。糖尿病小鼠模型构建完成后，GQD高剂量组以10.14 g·kg^-1·d^-1的剂量灌胃葛根芩连汤水提取液，正常对照组和模型对照组灌胃等体积ddH₂O。与正常对照组相比，^* P<0.05；与模型对照组相比，^# P<0.05。

Figure 3 

Note： A–E， Serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， C-X-C motif chemokine ligand 2 （CXCL2）， high mobility group box-1 （HMGB1）， and monocyte chemoattractant protein-1 （MCP-1） in mice of each group were detected by ELISA （n=6）. Mice in the model groups （model control group and GQD high-dose group） were fed a 60% high-fat diet and 5% glucose water for 4 weeks. After 12 h of fasting， 100 mg/kg STZ （dissolved in citrate buffer） was administered intraperitoneally to establish a type 2 diabetes mellitus model. Mice in the normal control group were given regular chow and drinking water， and received an equal volume of citrate buffer by intraperitoneal injection after 12 h of fasting at the same time point. After successful model establishment， mice in the GQD high-dose group were intragastrically given an aqueous extract of Gegen Qinlian decoction at a dose of 10.14 g·kg^-1·d^-1. The normal control group and model control group were intragastrically administered with an equal volume of ddH₂O. Compared with normal control group， ^* P<0.05； compared with model control group， ^# P<0.05.

图4 

注：小鼠心肌组织WGA染色代表图（A）、心肌细胞横截面积定量分析（B）及HE染色代表图（C）。造模组（模型对照组、GQD低剂量组、GQD中剂量组、GQD高剂量组和阳性对照组）小鼠以60%高脂饲料+5%葡萄糖水喂养4周，禁食12 h后腹腔注射100 mg/kg STZ（使用柠檬酸盐缓冲液配制）诱导2型糖尿病动物模型；正常对照组给予普通饲料、饮水，并同期禁食12 h后腹腔注射等体积柠檬酸盐缓冲液。糖尿病小鼠模型构建完成后，GQD低剂量组、GQD中剂量组、GQD高剂量组分别以2.53 g·kg^-1·d^-1、5.07 g·kg^-1·d^-1、10.14 g·kg^-1·d^-1的剂量灌胃葛根芩连汤水提取液，阳性对照组以0.20 g·kg^-1·d^-1剂量灌胃二甲双胍，正常对照组和模型对照组灌胃等体积ddH₂O。GQD，葛根芩连汤。标尺=50 μm，n=6；与正常对照组相比，^* P<0.05；与模型对照组相比，^# P<0.05。

Figure 4 

Note： Representative images of WGA staining （A）， quantitative analysis of cardiomyocyte cross-sectional area （B）， and representative images of HE staining （C） in mouse myocardial tissue. Mice in the model groups （model control group， GQD low-dose group， GQD medium-dose group， GQD high-dose group， and positive control group） were fed a 60% high-fat diet and 5% glucose water for 4 weeks. After 12 h of fasting， 100 mg/kg STZ （dissolved in citrate buffer） was administered intraperitoneally to establish a type 2 diabetes mellitus model. Mice in the normal control group were given regular chow and drinking water， and received an equal volume of citrate buffer by intraperitoneal injection after 12 h of fasting at the same time point. After successful model establishment， mice in the GQD low-dose， medium-dose， and high-dose groups were intragastrically given an aqueous extract of Gegen Qinlian decoction at doses of 2.53 g·kg^-1·d^-1， 5.07 g·kg^-1·d^-1， and 10.14 g·kg^-1·d^-1， respectively. Mice in the positive control group were intragastrically administered metformin at a dose of 0.20 g·kg^-1·d^-1. The normal control group and model control group were intragastrically administered an equal volume of ddH₂O. GQD， Gegen Qinlian decoction. Scale bar=50 μm； n=6； ^* P<0.05 vs. normal control group； ^# P<0.05 vs. model control group.

图5 

注：小鼠心肌组织中晚期糖基化终末产物受体（RAGE）、核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3（NLRP3）以及磷酸化核转录因子p65（p-p65）蛋白的免疫组织化学染色结果（A）及其定量分析结果（B～D）。造模组（模型对照组、GQD高剂量组）小鼠以60%高脂饲料+5%葡萄糖水喂养4周，禁食12 h后腹腔注射100 mg/kg STZ（使用柠檬酸盐缓冲液配制）诱导2型糖尿病动物模型；正常对照组给予普通饲料、饮水，并同期禁食12 h后腹腔注射等体积柠檬酸盐缓冲液。糖尿病小鼠模型构建完成后，GQD高剂量组以10.14 g·kg^-1·d^-1的剂量灌胃GQD水提取液，正常对照组和模型对照组灌胃等体积ddH₂O。GQD，葛根芩连汤。标尺=50 μm；n=6；与正常对照组相比， ^*P<0.05；与模型对照组相比，^# P<0.05。

Figure 5 

Note： Immunohistochemical staining results （A） and quantitative analysis （B-D） of receptor for advanced glycation end products （RAGE）， nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）， and phosphorylated nuclear factor-κB p65 （p-p65） proteins in mouse myocardial tissue. Mice in the model groups （model control group and GQD high-dose group） were fed with 60% high-fat diet and 5% glucose water for 4 weeks. After 12 h of fasting， 100 mg/kg STZ （prepared in citrate buffer） was intraperitoneally injected to establish a type 2 diabetes mellitus animal model. Mice in the normal control group received regular chow and drinking water， and were intraperitoneally injected with an equal volume of citrate buffer after 12 h of fasting at the same time point. After successful establishment of the diabetic mouse model， mice in the GQD high-dose group were intragastrically administered with an aqueous extract of Gegen Qinlian decoction at a dose of 10.14 g·kg^-1·d^-1. The normal control group and model control group received an equal volume of ddH₂O by gavage. GQD， Gegen Qinlian decoction. Scale bar=50 μm； n=6； ^*P < 0.05 vs. normal control group； ^# P<0.05 vs. model control group.