Journal of Traditional Chinese Medicine ›› 2024, Vol. 44 ›› Issue (3): 545-553.DOI: 10.19852/j.cnki.jtcm.20240308.004
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Clinical efficacy and gene chip expression analysis of Shenzhu Guanxin recipe granules (参术冠心方颗粒) in patients with intermediate coronary lesions
JIN Xiao1, WU Bingxin2, LIN Miaoyang2, ZHONG Biying2, LIN Luoqi2, XU Danping3(
)
- 1 Department of Traditional Chinese Medicine, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510630, China
2 Department of Cardiology, Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China
3 Department of Traditional Chinese Medicine, the Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518033, China
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Received:2022-10-22Accepted:2023-02-10Online:2024-06-15Published:2024-03-08 -
Contact:XU Danping, Department of Traditional Chinese Medicine, the Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518033, China.xudanping@hotmail.com Telephone: +86-755-83982222 -
Supported by:Traditional Chinese Medicine Bureau of Guangdong Province: Research on the Mechanism of Shen Shu Guan Xin Fang in Reducing Hypoxia Induced Myocardial Cell Injury by Regulating miR-24(20221108);Science and Technology Projects in Guangzhou: Exploring the Intervention of Shenzhu Guanxin Formula on Myocardial Ischemia Based on MiR-24 Mediated Bim/Caspase Apoptosis Signal Pathway Mechanism Research(202201010521);Science and Technology Innovation Projects of Shenzhen: to Study the Mechanism of Hesperidin in Improving Heart Failure Based on Myocardial Inflammation Mediated by MtDNA-sGAS-STING Signaling Pathway(JCYJ20220530144212026);Futian Healthcare Research Project: To Study the Anti-atherosclerosis Effects and Mechanism of Shenzhu Guanxin Decoction on Inhibiting Platelet-mediated Inflammation Based on the Theory of "Phlegm-stasis Interjunction"(FTWS2022012)
Cite this article
JIN Xiao, WU Bingxin, LIN Miaoyang, ZHONG Biying, LIN Luoqi, XU Danping. Clinical efficacy and gene chip expression analysis of Shenzhu Guanxin recipe granules (参术冠心方颗粒) in patients with intermediate coronary lesions[J]. Journal of Traditional Chinese Medicine, 2024, 44(3): 545-553.
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Figure 1 Study flow diagram SGR: Shenshu Guanxin recipe granules.
Figure 1 Study flow diagram SGR: Shenshu Guanxin recipe granules.
Table 1 Comparison of baseline characteristics between the two groups ($\bar{x} \pm s$)
| Item | Case (n = 30) | Control (n = 30) | Statistical value | P value |
|---|---|---|---|---|
| Age (years) | 61.1±7.6 | 63.7±6.5 | 1.409 | 0.238 |
| Gender (male/female, n) | 9:21 | 12:18 | 0.659 | 0.417 |
| Height (cm) | 165.0±7.5 | 164.4±7.6 | -0.354 | 0.574 |
| Weight (kg) | 64.4±8.0 | 60.6±7.1 | -1.924 | 0.059 |
| Disease course (years) | 3.1±3.5 | 2.0±1.7 | -1.62 | 0.111 |
Table 1 Comparison of baseline characteristics between the two groups ($\bar{x} \pm s$)
| Item | Case (n = 30) | Control (n = 30) | Statistical value | P value |
|---|---|---|---|---|
| Age (years) | 61.1±7.6 | 63.7±6.5 | 1.409 | 0.238 |
| Gender (male/female, n) | 9:21 | 12:18 | 0.659 | 0.417 |
| Height (cm) | 165.0±7.5 | 164.4±7.6 | -0.354 | 0.574 |
| Weight (kg) | 64.4±8.0 | 60.6±7.1 | -1.924 | 0.059 |
| Disease course (years) | 3.1±3.5 | 2.0±1.7 | -1.62 | 0.111 |
Table 2 Related indexes of CCTA ($\bar{x} \pm s$)
| Index | Case (n = 30) | Control (n = 30) | P value between the groups after treatment | |||||
|---|---|---|---|---|---|---|---|---|
| Before treatment | After treatment | Before treatment | After treatment | |||||
| Transmural gradient of Myocardial perfusion | 1.00±0.10 | 1.01±0.07 | 0.98±0.10 | 1.00±0.12 | 0.642 | |||
| CT value of aortic root | 626.89±132.43 | 663.87±127.10 | 660.30±98.49 | 675.47±89.97 | 0.685 | |||
| CT value of left ventricular | 576.74±160.36 | 638.67±178.49 | 604.32±173.25 | 620.09±156.78 | 0.670 | |||
Table 2 Related indexes of CCTA ($\bar{x} \pm s$)
| Index | Case (n = 30) | Control (n = 30) | P value between the groups after treatment | |||||
|---|---|---|---|---|---|---|---|---|
| Before treatment | After treatment | Before treatment | After treatment | |||||
| Transmural gradient of Myocardial perfusion | 1.00±0.10 | 1.01±0.07 | 0.98±0.10 | 1.00±0.12 | 0.642 | |||
| CT value of aortic root | 626.89±132.43 | 663.87±127.10 | 660.30±98.49 | 675.47±89.97 | 0.685 | |||
| CT value of left ventricular | 576.74±160.36 | 638.67±178.49 | 604.32±173.25 | 620.09±156.78 | 0.670 | |||
Table 3 Comparison of level of blood lipids ($\bar{x} \pm s$)
| Group | Time | Triglycerides | Total Cholesterol | Low Density Lipoprotein | High Density Lipoprotein |
|---|---|---|---|---|---|
| Case (n =30) | Before treatment | 1.5±0.7 | 4.4±1.0 | 2.8±0.9 | 1.2±0.3 |
| After treatment | 1.5±0.8 | 3.7±0.5ab | 2.4±0.6ab | 1.3±0.5 | |
| Control (n =30) | Before treatment | 1.8±1.5 | 4.7±1.2 | 3.0±1.1 | 1.3±0.4 |
| After treatment | 1.9±1.1 | 4.2±0.7ab | 2.8±0.7ab | 1.2±0.4 |
Table 3 Comparison of level of blood lipids ($\bar{x} \pm s$)
| Group | Time | Triglycerides | Total Cholesterol | Low Density Lipoprotein | High Density Lipoprotein |
|---|---|---|---|---|---|
| Case (n =30) | Before treatment | 1.5±0.7 | 4.4±1.0 | 2.8±0.9 | 1.2±0.3 |
| After treatment | 1.5±0.8 | 3.7±0.5ab | 2.4±0.6ab | 1.3±0.5 | |
| Control (n =30) | Before treatment | 1.8±1.5 | 4.7±1.2 | 3.0±1.1 | 1.3±0.4 |
| After treatment | 1.9±1.1 | 4.2±0.7ab | 2.8±0.7ab | 1.2±0.4 |
Table 4 Comparison of Seattle Angina scale scores ($\bar{x} \pm s$)
| Group | Time | PL | AS | AF | TS | DP |
|---|---|---|---|---|---|---|
| Case (n = 30) | Before treatment | 65±19 | 43±16 | 55±20 | 62±17 | 37±14 |
| After treatment | 78±18ab | 55±20ab | 76±17ab | 75±14ab | 51±18ab | |
| Control (n = 30) | Before treatment | 64±19 | 43±14 | 56±18 | 61±15 | 38±15 |
| After treatment | 65±17ab | 47±16ab | 56±15ab | 63±15ab | 39±13ab |
Table 4 Comparison of Seattle Angina scale scores ($\bar{x} \pm s$)
| Group | Time | PL | AS | AF | TS | DP |
|---|---|---|---|---|---|---|
| Case (n = 30) | Before treatment | 65±19 | 43±16 | 55±20 | 62±17 | 37±14 |
| After treatment | 78±18ab | 55±20ab | 76±17ab | 75±14ab | 51±18ab | |
| Control (n = 30) | Before treatment | 64±19 | 43±14 | 56±18 | 61±15 | 38±15 |
| After treatment | 65±17ab | 47±16ab | 56±15ab | 63±15ab | 39±13ab |
Table 5 Comparison of TCM syndrome score and the level of hsCRP ($\bar{x} \pm s$)
| Item | Group | n | Before treatment | After treatment | P value compared with baseline | P value between the groups |
|---|---|---|---|---|---|---|
| TCM syndrome score | Case | 30 | 15.7±6.0 | 5.9±3.5 | <0.001 | 0.011 |
| Control | 30 | 14.9±5.9 | 8.3±4.3 | <0.001 | ||
| hs-CRP | Case | 30 | 1.8±1.7 | 3.7±2.7 | 0.162 | 0.426 |
| Control | 30 | 4.6±3.2 | 3.2±2.0 | 0.183 |
Table 5 Comparison of TCM syndrome score and the level of hsCRP ($\bar{x} \pm s$)
| Item | Group | n | Before treatment | After treatment | P value compared with baseline | P value between the groups |
|---|---|---|---|---|---|---|
| TCM syndrome score | Case | 30 | 15.7±6.0 | 5.9±3.5 | <0.001 | 0.011 |
| Control | 30 | 14.9±5.9 | 8.3±4.3 | <0.001 | ||
| hs-CRP | Case | 30 | 1.8±1.7 | 3.7±2.7 | 0.162 | 0.426 |
| Control | 30 | 4.6±3.2 | 3.2±2.0 | 0.183 |
Figure 2 Heatmap of differentially expressed mRNA, lncRNA and circRNA A: heatmap of differentially expressed mRNA; B: heatmap of differentially expressed lncRNA; C: heatmap of differentially expressed mRNA; mRNA: messenger RNA; lncRNA: long noncoding RNA; circRNA: circular RNA.
Figure 2 Heatmap of differentially expressed mRNA, lncRNA and circRNA A: heatmap of differentially expressed mRNA; B: heatmap of differentially expressed lncRNA; C: heatmap of differentially expressed mRNA; mRNA: messenger RNA; lncRNA: long noncoding RNA; circRNA: circular RNA.
Table 6 15 differentially expressed mRNA with the largest |log2FC| value
| GeneSymbol | P value | log2FC | Regulation |
|---|---|---|---|
| CD300H | 0.04908781 | -1.744017293 | Down |
| LOC283710 | 0.018101732 | -1.433638427 | Down |
| SLC22A1 | 0.019721809 | -1.42412257 | Down |
| SYTL4 | 0.002548443 | -1.382725044 | Down |
| CACNA1G | 0.044140794 | -1.355298456 | Down |
| ARHGEF10L | 0.03580098 | -1.254431345 | Down |
| TRIM7 | 0.027705062 | -1.241346051 | Down |
| OXTR | 0.019750795 | -1.240223741 | Down |
| CLEC12B | 0.039680333 | -1.227144764 | Down |
| ISL2 | 0.009444028 | -1.210483082 | Down |
| FAM20C | 0.041784465 | -1.169360968 | Down |
| PSRC1 | 0.021503422 | -1.165172062 | Down |
| ZDHHC11B | 0.004670639 | -1.149811385 | Down |
| CERS3 | 0.024225718 | -1.121712191 | Down |
| MXRA7 | 0.028407665 | -1.112152037 | Down |
| ULK3 | 0.048575733 | 1.012987918 | Up |
| MAGEA4 | 0.043658212 | 1.01443464 | Up |
| VPS33B | 0.014616993 | 1.01854859 | Up |
| OR13H1 | 0.006583539 | 1.02698403 | Up |
| FRMD1 | 0.018293367 | 1.061581726 | Up |
| COL11A2 | 0.009761185 | 1.067258947 | Up |
| GRAMD1C | 0.010157319 | 1.077156038 | Up |
| PCDHGA8 | 0.036312011 | 1.109755398 | Up |
| LGI4 | 0.026822805 | 1.123034554 | Up |
| KRT40 | 0.013562152 | 1.126128641 | Up |
| CCDC62 | 0.03875718 | 1.132531901 | Up |
| DNAJC6 | 0.043068924 | 1.146810891 | Up |
| MTRNR2L4 | 0.040007032 | 1.176296984 | Up |
| SLC28A1 | 0.048143021 | 1.177818657 | Up |
| MAS1L | 0.031043932 | 1.190467029 | Up |
Table 6 15 differentially expressed mRNA with the largest |log2FC| value
| GeneSymbol | P value | log2FC | Regulation |
|---|---|---|---|
| CD300H | 0.04908781 | -1.744017293 | Down |
| LOC283710 | 0.018101732 | -1.433638427 | Down |
| SLC22A1 | 0.019721809 | -1.42412257 | Down |
| SYTL4 | 0.002548443 | -1.382725044 | Down |
| CACNA1G | 0.044140794 | -1.355298456 | Down |
| ARHGEF10L | 0.03580098 | -1.254431345 | Down |
| TRIM7 | 0.027705062 | -1.241346051 | Down |
| OXTR | 0.019750795 | -1.240223741 | Down |
| CLEC12B | 0.039680333 | -1.227144764 | Down |
| ISL2 | 0.009444028 | -1.210483082 | Down |
| FAM20C | 0.041784465 | -1.169360968 | Down |
| PSRC1 | 0.021503422 | -1.165172062 | Down |
| ZDHHC11B | 0.004670639 | -1.149811385 | Down |
| CERS3 | 0.024225718 | -1.121712191 | Down |
| MXRA7 | 0.028407665 | -1.112152037 | Down |
| ULK3 | 0.048575733 | 1.012987918 | Up |
| MAGEA4 | 0.043658212 | 1.01443464 | Up |
| VPS33B | 0.014616993 | 1.01854859 | Up |
| OR13H1 | 0.006583539 | 1.02698403 | Up |
| FRMD1 | 0.018293367 | 1.061581726 | Up |
| COL11A2 | 0.009761185 | 1.067258947 | Up |
| GRAMD1C | 0.010157319 | 1.077156038 | Up |
| PCDHGA8 | 0.036312011 | 1.109755398 | Up |
| LGI4 | 0.026822805 | 1.123034554 | Up |
| KRT40 | 0.013562152 | 1.126128641 | Up |
| CCDC62 | 0.03875718 | 1.132531901 | Up |
| DNAJC6 | 0.043068924 | 1.146810891 | Up |
| MTRNR2L4 | 0.040007032 | 1.176296984 | Up |
| SLC28A1 | 0.048143021 | 1.177818657 | Up |
| MAS1L | 0.031043932 | 1.190467029 | Up |
Figure 3 Protein interaction network analysis and 10 hub genes map A: PPI network of all DEGs by STRING website, visualized by Cytoscape. The red nodes stand for upregulated genes while the green nodes stand for downregulated genes; B: top 10 hub genes filtered by cytohubba and combining 12 algorithms; C: significant modules identified from the whole PPI network by the molecular complex detection MCODE. PPI: protein-protein interaction network; DEGs: differentially expressed genes; MCODE: molecular complex detection.
Figure 3 Protein interaction network analysis and 10 hub genes map A: PPI network of all DEGs by STRING website, visualized by Cytoscape. The red nodes stand for upregulated genes while the green nodes stand for downregulated genes; B: top 10 hub genes filtered by cytohubba and combining 12 algorithms; C: significant modules identified from the whole PPI network by the molecular complex detection MCODE. PPI: protein-protein interaction network; DEGs: differentially expressed genes; MCODE: molecular complex detection.
Figure 4 GO enrichment analysis and KEGG analysis of differentially expressed mRNAs A: GO enrichment analysis of differentially expressed mRNAs; B: KEGG analysis of differentially expressed mRNAs. GO: gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; mRNAs: messanger RNAs.
Figure 4 GO enrichment analysis and KEGG analysis of differentially expressed mRNAs A: GO enrichment analysis of differentially expressed mRNAs; B: KEGG analysis of differentially expressed mRNAs. GO: gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; mRNAs: messanger RNAs.
Table 7 Comparison of mRNA gene expression (2 - ?? Ct) between Shenzhu Guanxin formula group and placebo group ($\bar{x} \pm s$)
| mRNA | Case (n = 4) | Control (n = 7) | P value |
|---|---|---|---|
| CEP72 | 2.57±0.37 | 1.11±0.71 | 0.004 |
| DDAH2 | 1.05±0.66 | 1.98±0.52 | 0.03 |
| HDAC5 | 1.33±0.28 | 0.70±0.10 | <0.001 |
| CD300A | 1.34±0.58 | 1.12±0.61 | 0.567 |
Table 7 Comparison of mRNA gene expression (2 - ?? Ct) between Shenzhu Guanxin formula group and placebo group ($\bar{x} \pm s$)
| mRNA | Case (n = 4) | Control (n = 7) | P value |
|---|---|---|---|
| CEP72 | 2.57±0.37 | 1.11±0.71 | 0.004 |
| DDAH2 | 1.05±0.66 | 1.98±0.52 | 0.03 |
| HDAC5 | 1.33±0.28 | 0.70±0.10 | <0.001 |
| CD300A | 1.34±0.58 | 1.12±0.61 | 0.567 |
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