1.Quality control mechanism of mitochondria by 3,4-dihydroxybenzaldehyde through OGT-PINK1 pathway.
Yuan LUO ; Pu CHEN ; Li-Ping YANG ; Xiao-Hua DUAN
China Journal of Chinese Materia Medica 2023;48(12):3308-3316
Based on the O-GlcNAc transferase(OGT)-PTEN-induced putative kinase 1(PINK1) pathway, the mechanism of 3,4-dihydroxybenzaldehyde(DBD) on mitochondrial quality control was investigated. Middle cerebral artery occlusion/reperfusion(MCAO/R) rats were established. SD rats were randomized into sham operation group(sham), model group(MCAO/R), DBD-L group(5 mg·kg~(-1)), and DBD-H group(10 mg·kg~(-1)). After 7 days of administration(ig), MCAO/R was induced in rats except the sham group with the suture method. Twenty-four h after reperfusion, the neurological function and the percentage of cerebral infarct area were measured. Based on hematoxylin and eosin(HE) staining and Nissl staining, the pathological damage of cerebral neurons was examined. Then the ultrastructure of mitochondria was observed under the electron microscope, and the co-localization of light chain-3(LC3), sequestosome-1(SQSTM1/P62), and Beclin1 was further detected by immunofluorescence staining. It has been reported that the quality of mitochondria can be ensured by inducing mitochondrial autophagy through the OGT-PINK1 pathway. Therefore, Western blot was employed to detect the expression of OGT, mitophagy-related proteins PINK1 and E3 ubiquitin ligase(Parkin), and mitochondrial kinetic proteins dynamin-like protein 1(Drp1) and optic atrophy 1(Opa1). The results showed that MCAO/R group had neurological dysfunction, large cerebral infarct area(P<0.01), damaged morphological structure of neurons, decreased number of Nissl bodies, mitochondrial swelling, disappearance of mitochondrial cristae, decrease of cells with LC3 and Beclin1, rise of cells with P62(P<0.01), inhibited expression of OGT, PINK1, and Parkin, up-regulated expression of Drp1, and down-regulated expression of Opa1 compared with the sham group(P<0.01). However, DBD improved the behavioral deficits and mitochondrial health of MCAO/R rats, as manifested by the improved morphology and structure of neurons and mitochondria and the increased Nissl bodies. Moreover, DBD increased cells with LC3 and Beclin1 and decreased cells with P62(P<0.01). In addition, DBD promoted the expression of OGT, PINK1, Parkin, and Opa1 and inhibited the expression of Drp1, enhancing mitophagy(P<0.05, P<0.01). In conclusion, DBD can trigger PINK1/Parkin-mediated brain mitophagy through the OGT-PINK1 pathway, which plays a positive role in maintaining the health of the mitochondrial network. This may be a mitochondrial therapeutic mechanism to promote nerve cell survival and improve cerebral ischemia/reperfusion injury.
Animals
;
Rats
;
Rats, Sprague-Dawley
;
Beclin-1
;
Mitochondria
;
Cerebral Infarction
;
Protein Kinases
2.Effect of Xiaoxuming Decoction on synaptic plasticity following acute cerebral ischemia-reperfusion in rats.
Xue-Qin FU ; Rui LAN ; Yong ZHANG ; Man-Man WANG ; Xu-Huan ZOU ; Wei-Wei WANG
China Journal of Chinese Materia Medica 2023;48(14):3882-3889
This study aims to explore the effect of Xiaoxuming Decoction on synaptic plasticity in rats with acute cerebral ischemia-reperfusion. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion(MCAO). Rats were randomly assigned into a sham group, a MCAO group, and a Xiaoxuming Decoction(60 g·kg~(-1)·d~(-1)) group. The Longa score was rated to assess the neurological function of rats with cerebral ischemia for 1.5 h and reperfusion for 24 h. The 2,3,5-triphenyltetrazolium chloride(TTC) staining and hematoxylin-eosin(HE) staining were employed to observe the cerebral infarction and the pathological changes of brain tissue after cerebral ischemia, respectively. Transmission electron microscopy was employed to detect the structural changes of neurons and synapses in the ischemic penumbra, and immunofluorescence, Western blot to determine the expression of synaptophysin(SYN), neuronal nuclei(NEUN), and postsynaptic density 95(PSD95) in the ischemic penumbra. The experimental results showed that the modeling increased the Longa score and led to cerebral infarction after 24 h of ischemia-reperfusion. Compared with the model group, Xiaoxuming Decoction intervention significantly decreased the Longa score and reduced the formation of cerebral infarction area. The modeling led to the shrinking and vacuolar changes of nuclei in the brain tissue, disordered cell arrangement, and severe cortical ischemia-reperfusion injury, while the pathological damage in the Xiaoxuming Decoction group was mild. The modeling blurred the synaptic boundaries and broadened the synaptic gap, while such changes were recovered in the Xiaoxuming Decoction group. The modeling decreased the fluorescence intensity of NEUN and SYN, while the intensity in Xiaoxuming Decoction group was significantly higher than that in the model group. The expression of SYN and PSD95 in the ischemic penumbra was down-regulated in the model group, while such down-regulation can be alleviated by Xiaoxuming Decoction. In summary, Xiaoxuming Decoction may improve the synaptic plasticity of ischemic penumbra during acute cerebral ischemia-reperfusion by up-regulating the expression of SYN and PSD95.
Rats
;
Animals
;
Rats, Sprague-Dawley
;
Brain Ischemia/drug therapy*
;
Reperfusion Injury/metabolism*
;
Infarction, Middle Cerebral Artery
;
Neuronal Plasticity
;
Reperfusion
3.Effective constituents of essential oil from Gleditsiae Fructus Abnormalis and anti-cerebral ischemia/reperfusion injury mechanism: based on GC-MS, network pharmacology, and experimental verification.
Na-Na DONG ; Xiao-Lan CHEN ; Bi-Li DENG ; Shu-Cai XIE ; Juan HU
China Journal of Chinese Materia Medica 2023;48(4):1076-1086
Based on GC-MS and network pharmacology, the active constituents, potential targets, and mechanism of essential oil from Gleditsiae Fructus Abnormalis(EOGFA) against cerebral ischemia/reperfusion(I/R) injury were explored, and the effective constituents were verified by experiment. To be specific, GC-MS was used identify the constituents of the volatile oil. Secondly, the targets of the constituents and disease were predicted by network pharmacology, and the drug-constituent-target network was constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets. Molecular docking was performed to investigate the binding affinity between the active constituents and the targets. Finally, SD rats were used for experimental verification. The I/R injury model was established, and the neurological behavior score, infarct volume, and pathological morphology of brain tissue were measured in each group. The content of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression of vascular endothelial growth factor(VEGF) by Western blot. A total of 22 active constituents and 17 core targets were screened out. The core targets were involved in 56 GO terms and the major KEGG pathways of TNF signaling pathway, VEGF signaling pathway, and sphingolipid signaling pathway. Molecular docking showed that the active constituents had high affinity to the targets. The results of animal experiment suggested that EOGFA can alleviate the neurological impairment, decrease the cerebral infarct volume and the content of IL-1β, IL-6 and TNF-α, and down-regulate the expression of VEGF. The experiment verified the part results of network pharmacology. This study reflects the multi-component, multi-target, and multi-pathway characteristics of EOGFA. The mechanism of its active constituents is related to TNF and VEGF pathways, which provides a new direction for in-depth research on and secondary development of Gleditsiae Fructus Abnormalis.
Animals
;
Rats
;
Rats, Sprague-Dawley
;
Network Pharmacology
;
Oils, Volatile
;
Gas Chromatography-Mass Spectrometry
;
Interleukin-6
;
Molecular Docking Simulation
;
Tumor Necrosis Factor-alpha
;
Vascular Endothelial Growth Factor A
;
Reperfusion Injury
;
Cerebral Infarction
4.Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats.
Dan-Ni LU ; Qian XIE ; Zhuo XU ; Jian-Mei YUAN ; Rong MA ; Jian WANG
China Journal of Chinese Materia Medica 2023;48(5):1289-1299
This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-β1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-β1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol > synthetic borneol > natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.
Rats
;
Male
;
Animals
;
Transforming Growth Factor beta1/metabolism*
;
Rats, Sprague-Dawley
;
Tumor Necrosis Factor-alpha/metabolism*
;
Interleukin-6/metabolism*
;
Interleukin-4/metabolism*
;
Polysorbates
;
Brain
;
Brain Ischemia/metabolism*
;
Reperfusion Injury/metabolism*
;
Cerebral Infarction
;
Reperfusion
5.CiteSpace knowledge map analysis of Angong Niuhuang Pills in recent twenty years.
Xue BAI ; Fei-Fei GUO ; Lin TONG ; Hong-Jun YANG
China Journal of Chinese Materia Medica 2023;48(5):1381-1392
Angong Niuhuang Pills, a classical formula in traditional Chinese medicine, are lauded as one of the "three treasures of febrile diseases" and have been widely used in the treatment of diverse disorders with definite efficacy. However, there is still a lack of bibliometric analysis of research progress and development trend regarding Angong Niuhuang Pills. Research articles on Angong Niuhuang Pills in China and abroad(2000-2022) were retrieved from CNKI and Web of Science. CiteSpace 6.1 was used to visualize the key contents of the research articles. In addition, the research status of Angong Niuhuang Pills was analyzed by information extraction to allow insight into the research trends and hotspots about Angong Niuhuang Pills. A total of 460 Chinese articles and 41 English articles were included. Beijing University of Chinese Medicine and Sun Yat-Sen University were the research institutions that have published the largest amount of research articles in Chinese and English. The keyword analysis showed that the Chinese articles focused on cerebral hemorrhage, stroke, neurological function, coma, cerebral infarction, craniocerebral injury, and clinical application, while the English articles focused on the mechanisms of cerebral ischemia, stroke, heavy metal, blood-brain barrier, and oxidative stress. Stroke, blood-brain barrier, and oxidative stress were presumably the research hotspots in the future. At present, the research on Angong Niuhuang Pills is still in the developing stage. It is necessary to highlight the in-depth research on the active components and mechanism of action and carry out large-scale randomized controlled clinical trials to provide references for the further development and application of Angong Niuhuang Pills.
Humans
;
Drugs, Chinese Herbal/therapeutic use*
;
Stroke/drug therapy*
;
Medicine, Chinese Traditional
;
Brain Ischemia/drug therapy*
;
Cerebral Infarction/drug therapy*
6.Bombyx Batryticatus extract promotes microglia polarization to improve neuron injury and behaviors of cerebral ischemia/reperfusion rats.
Pei-Mei HOU ; Hao XU ; Ze-Kang LI ; Hao ZHOU ; Shan-Shan WANG ; Jin-Wen GE
China Journal of Chinese Materia Medica 2023;48(6):1589-1596
This study aims to investigate the effect of Bombyx Batryticatus extract(BBE) on behaviors of rats with global cerebral ischemia reperfusion(I/R) and the underlying mechanism. The automatic coagulometer was used to detect the four indices of human plasma coagulation after BBE intervention for quality control of the extract. Sixty 4-week-old male SD rats were randomized into sham operation group(equivalent volume of normal saline, ip), model group(equivalent volume of normal saline, ip), positive drug group(900 IU·kg~(-1) heparin, ip), and low-, medium-, and high-dose BBE groups(0.45, 0.9, and 1.8 mg·g~(-1)·d~(-1) BBE, ip). Except the sham operation group, rats were subjected to bilateral common carotid artery occlusion followed by reperfusion(BCCAO/R) to induce I/R. The administration lasted 7 days for all the groups. The behaviors of rats were examined by beam balance test(BBT). Morphological changes of brain tissue were observed based on hematoxylin-eosin(HE) staining. Immunofluorescence method was used to detect common leukocyte antigen(CD45), leukocyte differentiation antigen(CD11b), and arginase-1(Arg-1) in cerebral cortex(CC). The protein expression of interleukin-1β(IL-1β), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) was detected by enzyme-linked immunosorbent assay(ELISA). The non-targeted metabonomics was employed to detect the levels of metabolites in plasma and CC of rats after BBE intervention. The results of quality control showed that the BBE prolonged the activated partial thromboplastin time(APTT), prothrombin time(PT), and thrombin time(TT) of human plasma, which was similar to the anticoagulation effect of BBE obtained previously. The results of behavioral test showed that the BBT score of the model group increased compared with that of the sham operation group. Compared with the model group, BBE reduced the BBT score. As for the histomorphological examination, compared with the sham operation group, the model group showed morphological changes of a lot of nerve cells in CC. The nerve cells with abnormal morphology in CC decreased after the intervention of BBE compared with those in the model group. Compared with the sham operation group, the model group had high average fluorescence intensity of CD45 and CD11b in the CC. The average fluorescence intensity of CD11b decreased and the average fluorescence intensity of Arg-1 increased in CC in the low-dose BBE group compared with those in the model group. The average fluorescence intensity of CD45 and CD11b decreased and the average fluorescence intensity of Arg-1 increased in medium-and high-dose BBE groups compared with those in the model group. The expression of IL-1β and IL-6 was higher and the expression of IL-4 and IL-10 was lower in the model group than in the sham operation group. The expression of IL-1β and IL-6 was lower and the expression of IL-4 and IL-10 was higher in the low-dose, medium-dose, and high-dose BBE groups than in the model group. The results of non-targeted metabonomics showed that 809 metabolites of BBE were identified, and 57 new metabolites in rat plasma and 45 new metabolites in rat CC were found. BBE with anticoagulant effect can improve the behaviors of I/R rats, and the mechanism is that it promotes the polarization of microglia to M2 type, enhances its anti-inflammatory and phagocytic functions, and thus alleviates the damage of nerve cells in CC.
Humans
;
Rats
;
Male
;
Animals
;
Interleukin-10
;
Rats, Sprague-Dawley
;
Interleukin-4/metabolism*
;
Bombyx
;
Interleukin-6/metabolism*
;
Microglia/metabolism*
;
Saline Solution/metabolism*
;
Reperfusion Injury/metabolism*
;
Brain Ischemia/metabolism*
;
Cerebral Infarction
;
Reperfusion
;
Neurons
7.Chrysin alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis in rats.
Jin-Feng SHANG ; Jia-Kang JIAO ; Qian-Nan LI ; Ying-Hui LU ; Jing-Yi WANG ; Ming-Xue YAN ; Yin-Lian WEN ; Gui-Jin-Feng HUANG ; Xiao-Lu ZHANG ; Xin LIU
China Journal of Chinese Materia Medica 2023;48(6):1597-1605
The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.
Rats
;
Male
;
Animals
;
Rats, Sprague-Dawley
;
Ferroptosis
;
Signal Transduction
;
Brain Ischemia/metabolism*
;
Cyclooxygenase 2/metabolism*
;
RNA, Messenger
;
Cerebral Infarction
;
Reperfusion Injury/metabolism*
;
Malondialdehyde
;
Infarction, Middle Cerebral Artery
8.Effects of electro-scalp acupuncture on inflammatory response and microglial polarization in the ischemic cortex of rats with ischemic stroke.
Xiao-Yun PENG ; Bo YUAN ; Tian TIAN ; Wen-Jun LUO ; Ling-Gui ZHU ; Yan-Ju ZHANG ; Ying LI ; Xiao-Zheng DU ; Jin-Hai WANG
Chinese Acupuncture & Moxibustion 2023;43(9):1050-1055
OBJECTIVE:
To observe the effects of electro-scalp acupuncture (ESA) on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1β, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke.
METHODS:
Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD3 group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD3 group were treated with intragastric administration of 1,25-dihydroxyvitamin D3 (1,25-VitD3) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1β, and IL-10 in the ischemic cortex.
RESULTS:
Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores (P<0.01), increased brain infarct volume (P<0.01), increased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the model group, both the ESA group and the VitD3 group showed decreased neurological deficit scores and neurobehavioral scores (P<0.01), reduced brain infarct volume (P<0.01), decreased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the VitD3 group, the ESA group had lower neurological deficit score (P<0.05), larger brain infarct volume (P< 0.05), and lower protein expression of CD32, CD206, IL-1β, and IL-10 in the ischemic cortex (P<0.01, P<0.05).
CONCLUSION
ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.
Male
;
Animals
;
Rats
;
Rats, Sprague-Dawley
;
Ischemic Stroke
;
Interleukin-10
;
Interleukin-6/genetics*
;
Microglia
;
Scalp
;
Acupuncture Therapy
;
Vitamins
;
Infarction, Middle Cerebral Artery
9.Effect of acupuncture on HIF-1α/NLRP3 inflammatory signaling pathway in the rats with cerebral ischemia-reperfusion injury.
Zheng-Yun CAI ; Xin-Chang ZHANG ; Fu-Rong LIU ; Zheng HUANG ; Meng-Ning YANG ; Pei-Yan HUANG ; Zhi-Hui ZHANG ; Guang-Xia NI
Chinese Acupuncture & Moxibustion 2023;43(9):1056-1061
OBJECTIVE:
To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury.
METHODS:
Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side.
RESULTS:
Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group.
CONCLUSION
Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.
Male
;
Animals
;
Rats
;
Rats, Sprague-Dawley
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
Acupuncture Therapy
;
Reperfusion Injury/therapy*
;
Brain Ischemia/therapy*
;
Cerebral Infarction/therapy*
;
NLR Proteins
10.Effects of zhongfeng cutong moxibustion on motor function and corticospinal tract in the patients with motor dysfunction during the recovery period of cerebral infarction.
Zi-Long ZHU ; Tian-Yi SHEN ; Zheng SUN ; Hao LI ; Hua SHAN ; Lin-Li CAO ; Jian-Bin ZHANG
Chinese Acupuncture & Moxibustion 2023;43(12):1358-1362
OBJECTIVES:
To observe the effects of zhongfeng cutong moxibustion (moxibustion therapy for unblocking and treating stroke) on the motor function and the structure of corticospinal tract (CST) in the patients with motor dysfunction during the recovery period of cerebral infarction, and to explore the central mechanism of this moxibustion therapy for improving the motor function.
METHODS:
Fifty patients with motor dysfunction during the recovery period of cerebral infarction were randomly divided into an observation group (25 cases, 1 case dropped out) and a control group (25 cases, 1 case dropped out). The patients in both groups underwent the conventional basic treatment. In the control group, acupuncture was applied to Baihui (GV 20) and Shuigou (GV 26), as well as Chize (LU 5), Neiguan (PC 6), Weizhong (BL 40) and Sanyinjiao (SP 6) etc. on the affected side. Besides the intervention of the control group, in the observation group, zhongfeng cutong moxibustion therapy was combined at Baihui (GV 20), Shenque (CV 8) and bilateral Zusanli (ST 36). Both acupuncture and moxibustion therapies were delivered once daily, 5 times a week, for 2 weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were compared between the two groups before and after treatment. The diffusion tensor imaging technique was used to observe the fractional anisotropy (FA) of CST at the bilateral whole segment, the cerebral cortex, the posterior limb of the internal capsule and the cerebral peduncle before and after treatment in the two groups.
RESULTS:
The scores of the upper and the lower limbs of FMA, as well as the total FMA score swere increased after treatment when compared with those before treatment in the two groups (P<0.05), the upper limb FMA score and the total FMA score in the observation group were higher than those in the control group (P<0.05), and NIHSS scores of the two groups were dropped compared with those before treatment (P<0.01). FA of CST at the bilateral sides of the posterior limb of the internal capsule and the whole segment on the focal side was improved in comparison with that before treatment in the observation group (P<0.05), and FA of CST at the healthy side of the whole segment was higher than that before treatment in the control group (P<0.05).
CONCLUSIONS
Zhongfeng cutong moxibustion improves motor function and reduces neurological deficits in the patients with motor dysfunction during the recovery period of cerebral infarction, which may be related to enhancing the remodeling of white matter fiber bundles in the corticospinal tract on the focal side of the whole segment and the bilateral posterior limb of the internal capsule.
Humans
;
Moxibustion
;
Pyramidal Tracts
;
Diffusion Tensor Imaging
;
Acupuncture Therapy
;
Cerebral Infarction/therapy*
;
Stroke/therapy*
;
Acupuncture Points
;
Treatment Outcome

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