Journal of Traditional Chinese Medicine ›› 2024, Vol. 44 ›› Issue (4): 680-687.DOI: 10.19852/j.cnki.jtcm.20240515.005
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Tongqiao Yizhi granule (通窍益智颗粒) repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats
LI Yanjiao1, HAO Linyao1, LI Shuangyang2, LUO Yanqi1, WANG Juan1, WANG Raoqiong2,3(
), BAI Xue2()
- 1 College of Integrative Medicine, Southwest Medical University, Luzhou 646600, China
2 Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China
3 Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, China
-
Received:2023-03-22Accepted:2023-07-24Online:2024-08-15Published:2024-05-15 -
Contact:Prof. BAI Xue, Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China.baixue@swmu.edu.cn Telephone: +86-13909081756; Prof. WANG Raoqiong, Department of Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, China.279424203@qq.com Telephone: +86-15228218357 -
Supported by:Sichuan Provincial Science and Technology Department Applied Basic Research Project: a Dynamic Contrast Enhanced Magnetic Resonance Imaging-based Study on the Effect of Eind Medicine Kaixuan Method on Blood-brain Barrier Function and Prognosis in Patients with Small to Medium Volume Cerebral Hemorrhage(2020YJ0437);Sichuan Provincial Administration of Traditional Chinese Medicine Science and Technology Special: Study on the Mechanism of Shexiang Huayu Xingnao Granules Reducing Nerve Injury in Cerebral Hemorrhage Model Rats by Regulating Microglia Polarization through Peroxisome Proliferator-activated Receptor γ(2021MS506);Luzhou Basic Application Project: the Mechanism of Tongqiao Yizhi Granules in the Treatment of Vascular Dementia by Regulating Gasdermin D-Mediated Pyroptosis(2020-JYJ-57)
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LI Yanjiao, HAO Linyao, LI Shuangyang, LUO Yanqi, WANG Juan, WANG Raoqiong, BAI Xue. Tongqiao Yizhi granule (通窍益智颗粒) repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats[J]. Journal of Traditional Chinese Medicine, 2024, 44(4): 680-687.
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Figure 1 Morris water maze test A: escape latency; B: residence time in the third quadrant; C: the number of platform crossings. Sham and Model group: treated with physiological saline; NMDP group: treated with nimodipine (6.25 mg·kg-1·d-1); 6.2, 12.4, 24.8 group: treated with TQYZKL (6.2 g·kg-1·d-1), TQYZKL (12.4 g·kg-1·d-1), TQYZKL (24.8 g·kg-1·d-1) respectively. NMDP: nimodipine; TQYZKL: Tongqiao Yizhi granule. Data are presented as mean ± standard error of the mean (n = 6). Significant differences compared with Sham group were designated as aP < 0.05, with Model group as bP < 0.05 and with NMDP group as cP < 0.05.
Figure 1 Morris water maze test A: escape latency; B: residence time in the third quadrant; C: the number of platform crossings. Sham and Model group: treated with physiological saline; NMDP group: treated with nimodipine (6.25 mg·kg-1·d-1); 6.2, 12.4, 24.8 group: treated with TQYZKL (6.2 g·kg-1·d-1), TQYZKL (12.4 g·kg-1·d-1), TQYZKL (24.8 g·kg-1·d-1) respectively. NMDP: nimodipine; TQYZKL: Tongqiao Yizhi granule. Data are presented as mean ± standard error of the mean (n = 6). Significant differences compared with Sham group were designated as aP < 0.05, with Model group as bP < 0.05 and with NMDP group as cP < 0.05.
Figure 2 TQYZKL alleviates neuronal pyroptosis in the hippocampus of VaD rats A: HE staining (× 400). A1, A7: Sham; A2, A8: Model; A3, A9: NMDP; A4, A10: TQYZKL of 6.2 g·kg-1·d-1; A5, A11: TQYZKL of 12.4 g·kg-1·d-1; A6, A12: TQYZKL of 24.8 g·kg-1·d-1; B: transmission electron microscope result: B1-B6 (× 8000); B7-B12 (× 20 000). B1, B7: Sham; B2, B8: Model; B3, B9: NMDP; B4, B10: TQYZKL of 6.2 g·kg-1·d-1; B5, B11: TQYZKL of 12.4 g·kg-1·d-1; B6, B12: TQYZKL of 24.8 g·kg-1·d-1; C: Tunel staining (× 200): C1, C7, C13: Sham; C2, C8, C14: Model; C3, C9, C15: NMDP; C4, C10, C16: TQYZKL of 6.2 g·kg-1·d-1; C5, C11, C17: TQYZKL of 12.4 g·kg-1·d-1; C6, C12, C18: TQYZKL of 24.8 g·kg-1·d-1; C1-C6: DAPI dyeing; C7-C12: Tunel dyeing; C13-C18: DAPI and tunel dyeing. Sham and Model group: treated with physiological saline; NMDP group: treated with nimodipine (6.25 mg·kg-1·d-1); 6.2, 12.4, 24.8 group: treated with TQYZKL (6.2 g·kg-1·d-1), TQYZKL (12.4 g·kg-1·d-1), TQYZKL (24.8 g·kg-1·d-1) respectively. VaD: vascular dementia. HE: hematoxylin-eosin; Tunel: terminal deoxynucleotidyl transferase dUTP nick end labeling; DAPI: 4',6-Diamidino-2-phenylindole; NMDP: nimodipine; TQYZKL: Tongqiao Yizhi granule.
Figure 2 TQYZKL alleviates neuronal pyroptosis in the hippocampus of VaD rats A: HE staining (× 400). A1, A7: Sham; A2, A8: Model; A3, A9: NMDP; A4, A10: TQYZKL of 6.2 g·kg-1·d-1; A5, A11: TQYZKL of 12.4 g·kg-1·d-1; A6, A12: TQYZKL of 24.8 g·kg-1·d-1; B: transmission electron microscope result: B1-B6 (× 8000); B7-B12 (× 20 000). B1, B7: Sham; B2, B8: Model; B3, B9: NMDP; B4, B10: TQYZKL of 6.2 g·kg-1·d-1; B5, B11: TQYZKL of 12.4 g·kg-1·d-1; B6, B12: TQYZKL of 24.8 g·kg-1·d-1; C: Tunel staining (× 200): C1, C7, C13: Sham; C2, C8, C14: Model; C3, C9, C15: NMDP; C4, C10, C16: TQYZKL of 6.2 g·kg-1·d-1; C5, C11, C17: TQYZKL of 12.4 g·kg-1·d-1; C6, C12, C18: TQYZKL of 24.8 g·kg-1·d-1; C1-C6: DAPI dyeing; C7-C12: Tunel dyeing; C13-C18: DAPI and tunel dyeing. Sham and Model group: treated with physiological saline; NMDP group: treated with nimodipine (6.25 mg·kg-1·d-1); 6.2, 12.4, 24.8 group: treated with TQYZKL (6.2 g·kg-1·d-1), TQYZKL (12.4 g·kg-1·d-1), TQYZKL (24.8 g·kg-1·d-1) respectively. VaD: vascular dementia. HE: hematoxylin-eosin; Tunel: terminal deoxynucleotidyl transferase dUTP nick end labeling; DAPI: 4',6-Diamidino-2-phenylindole; NMDP: nimodipine; TQYZKL: Tongqiao Yizhi granule.
Figure 3 TQYZKL ameliorates VaD through repressing the NF-κB/NLRP3/caspase-1 pathway by q-PCR and western blotting. A: mRNA levels of P65, NLRP3, caspase-1, GSDMD. A1: P65; A2: NLRP3; A3: caspase-1; A4: GSDMD; B: protein levels of P65, NLRP3, caspase-1, GSDMD-N. B1: P65; B2: protein levels of NLRP3; B3: caspase-1; B4: GSDMD; C: representative Western blot. Sham and Model group: treated with physiological saline; NMDP group: treated with nimodipine (6.25 mg·kg-1·d-1); 6.2, 12.4, 24.8 group: treated with TQYZKL (6.2 g·kg-1·d-1), TQYZKL (12.4 g·kg-1·d-1), TQYZKL (24.8 g·kg-1·d-1) respectively. TQYZKL: Tongqiao Yizhi granule; NF-κB: Nuclear factor kappa-B; NLRP3: nucleotide oligomerization domain-like receptors 3; q-PCR: quantitative real-time polymerase chain reaction; P65: GRASP65 protein; GSDMD: Gasdermin D; NMDP: nimodipine. Data are presented as mean ± standard error of the mean (n = 4). Significant differences compared with Sham group were designated as aP < 0.05, with Model group as bP < 0.05 and with NMDP group with cP < 0.05.
Figure 3 TQYZKL ameliorates VaD through repressing the NF-κB/NLRP3/caspase-1 pathway by q-PCR and western blotting. A: mRNA levels of P65, NLRP3, caspase-1, GSDMD. A1: P65; A2: NLRP3; A3: caspase-1; A4: GSDMD; B: protein levels of P65, NLRP3, caspase-1, GSDMD-N. B1: P65; B2: protein levels of NLRP3; B3: caspase-1; B4: GSDMD; C: representative Western blot. Sham and Model group: treated with physiological saline; NMDP group: treated with nimodipine (6.25 mg·kg-1·d-1); 6.2, 12.4, 24.8 group: treated with TQYZKL (6.2 g·kg-1·d-1), TQYZKL (12.4 g·kg-1·d-1), TQYZKL (24.8 g·kg-1·d-1) respectively. TQYZKL: Tongqiao Yizhi granule; NF-κB: Nuclear factor kappa-B; NLRP3: nucleotide oligomerization domain-like receptors 3; q-PCR: quantitative real-time polymerase chain reaction; P65: GRASP65 protein; GSDMD: Gasdermin D; NMDP: nimodipine. Data are presented as mean ± standard error of the mean (n = 4). Significant differences compared with Sham group were designated as aP < 0.05, with Model group as bP < 0.05 and with NMDP group with cP < 0.05.
Figure 4 TQYZKL ameliorates VaD through repressing the NF-κB/NLRP3/caspase-1 pathway by IHC and ELISA A: expression of caspase-1 protein in rat hippocampus (× 200); A1: Sham; A2: Model; A3: NMDP; A4: TQYZKL of 6.2 g·kg-1·d-1; A5: TQYZKL of 12.4 g·kg-1·d-1; A6: TQYZKL of 24.8 g·kg-1·d-1; B: expression of GSDMD protein in rat hippocampus (× 200), B1: Sham; B2: Model; B3: NMDP; B4: TQYZKL of 6.2 g·kg-1·d-1; B5: TQYZKL of 12.4 g·kg-1·d-1; B6: TQYZKL of 24.8 g·kg-1·d-1; Dyeing method of all pictures are the immunohistochemical method; C: expression of IL-18 and IL-1β in serum of rats. Sham and Model group: treated with physiological saline; NMDP group: treated with nimodipine (6.25 mg·kg-1·d-1); 6.2, 12.4, 24.8 group: treated with TQYZKL (6.2 g·kg-1·d-1), TQYZKL (12.4 g·kg-1·d-1), TQYZKL (24.8 g·kg-1·d-1) respectively. TQYZKL: Tongqiao Yizhi granule; NF-κB: nuclear factor kappa-B; NLRP3: nucleotide oligomerization domain-like receptors 3; IHC: immunohistochemistry; ELISA: enzyme-linked immunosorbent assay; IL-18: interleukin-18; IL-1β: interleukin-1β; NMDP: nimodipine. Data are presented as mean ± standard error of the mean (n = 4). Significant differences compared with Sham group were designated as aP < 0.05, with Model group as bP < 0.05 and with NMDP group with cP < 0.05.
Figure 4 TQYZKL ameliorates VaD through repressing the NF-κB/NLRP3/caspase-1 pathway by IHC and ELISA A: expression of caspase-1 protein in rat hippocampus (× 200); A1: Sham; A2: Model; A3: NMDP; A4: TQYZKL of 6.2 g·kg-1·d-1; A5: TQYZKL of 12.4 g·kg-1·d-1; A6: TQYZKL of 24.8 g·kg-1·d-1; B: expression of GSDMD protein in rat hippocampus (× 200), B1: Sham; B2: Model; B3: NMDP; B4: TQYZKL of 6.2 g·kg-1·d-1; B5: TQYZKL of 12.4 g·kg-1·d-1; B6: TQYZKL of 24.8 g·kg-1·d-1; Dyeing method of all pictures are the immunohistochemical method; C: expression of IL-18 and IL-1β in serum of rats. Sham and Model group: treated with physiological saline; NMDP group: treated with nimodipine (6.25 mg·kg-1·d-1); 6.2, 12.4, 24.8 group: treated with TQYZKL (6.2 g·kg-1·d-1), TQYZKL (12.4 g·kg-1·d-1), TQYZKL (24.8 g·kg-1·d-1) respectively. TQYZKL: Tongqiao Yizhi granule; NF-κB: nuclear factor kappa-B; NLRP3: nucleotide oligomerization domain-like receptors 3; IHC: immunohistochemistry; ELISA: enzyme-linked immunosorbent assay; IL-18: interleukin-18; IL-1β: interleukin-1β; NMDP: nimodipine. Data are presented as mean ± standard error of the mean (n = 4). Significant differences compared with Sham group were designated as aP < 0.05, with Model group as bP < 0.05 and with NMDP group with cP < 0.05.
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