scholarly journals A Study of the Molecular Mechanism by Which Substance P Enhances Doxorubicin (Adriamycin)-Associated Autophagy and Apoptosis of Cardiomyocytes Induces Heart Failure

2021 ◽  
Author(s):  
Fa-Xiu CHEN CHEN ◽  
Jian Hu ◽  
Jing Fang ◽  
Qing-Ling Li ◽  
Qin Wan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Substance P ◽  
Molecular Mechanisms ◽  
Sensory Nerves ◽  
Control Group ◽  
Model Group ◽  
Organ Systems ◽  
Wide Range ◽  
Group A ◽  
Antagonist Group

Abstract Background: Anthracyclines, including doxorubicin, are some of the most potent anticancer drugs available. However, the use of doxorubicin as a chemotherapeutic agent is severely hindered by dose-limiting toxicity, particularly cardiotoxicity, while degrading other organ systems. Despite years of use and the amount of details published on this drug, the understanding of its cellular mechanisms is still incomplete. Method: Cardiomyocyte grouping was carried out, where H9C2 cardiomyocytes were randomly divided into a control group, a myocardial model group, an SP group and an SP antagonist group. For replication in animal models, twelve rats were similarly divided randomly into a control group, a myocardial model group, an SP group, and an SP antagonist group. Except for the control group, the rats in the other groups were modelled: the rats were injected with adriamycin solution. Flow cytometry was used to detect apoptosis, while HE staining, TUNEL stain, Western Blot detection and transmission electron microscopy were performed to detect autophagy levels accordingly. All the results were analysed and carefully interpreted. Results: The tachykinin, substance P, is located mainly in sensory nerves and in the heart, where substance P-containing nerve fibres are often found around coronary vessels, making them ideally situated to detect changes in the myocardial environment. Apoptosis and autophagy are genetically-regulated, evolutionary-conserved processes that regulate cell fate and are both important for development, normal physiology, and a wide range of diseases. Recent studies show that despite the significant differences between these two processes, their regulation is closely connected and certain regulators have been found to be able to control both apoptosis and autophagy. Conclusions: In this study, the influence of substance P was discussed, providing possible molecular mechanisms for crosstalk between apoptosis and autophagy mediating heart failure due to Doxorubicin therapy. Trial registration: (20192BBGL7D031) 2019-09-17.

scholarly journals Substance P Enhances Doxorubicin (Adriamycin)-associated Autophagy and Reduces Cardiomyocyte Apoptosis.

2021 ◽  
Author(s):  
Fa-Xiu Chen ◽  
Jian Hu ◽  
Jing Fang ◽  
Qing-Ling Li ◽  
Qin Wan ◽  
...  
Keyword(s):  
Substance P ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Sensory Nerves ◽  
Control Group ◽  
Model Group ◽  
Organ Systems ◽  
Wide Range ◽  
Group A ◽  
Antagonist Group

Abstract BackgroundAnthracyclines, including doxorubicin, are some of the most potent anticancer drugs available. However, the use of doxorubicin as a chemotherapeutic agent is severely hindered by dose-limiting toxicity, particularly cardiotoxicity, while degrading other organ systems. Despite years of use and the number of details published on this drug, the understanding of its cellular mechanisms remains limited. MethodCardiomyocyte grouping was carried out, where H9C2 cardiomyocytes were randomly divided into a control group, a myocardial model group, an SP group, and an SP antagonist group. For replication in animal models, twelve rats were similarly randomly assigned into a control group, a myocardial model group, an SP group, and an SP antagonist group. Except for the control group, the rats in the other groups were modelled: the rats were injected with adriamycin solution. Flow cytometry was used to detect apoptosis, while HE staining, TUNEL stain, Western Blot detection, and transmission electron microscopy were performed to detect autophagy levels accordingly. All the results were analysed and carefully interpreted. Resultshe tachykinin, substance P, is located mainly in sensory nerves and in the heart, where substance P-containing nerve fibres are often found around coronary vessels, making them ideally situated to detect changes in the myocardial environment. Apoptosis and autophagy are genetically regulated, evolutionary-conserved processes that regulate cell fate and are important for development, normal physiology, and a wide range of diseases. Recent studies show that despite the significant differences between these two processes, their regulation is closely connected and certain regulators are able to control both apoptosis and autophagy. ConclusionsIn this study, the influence of substance P was discussed, providing possible molecular mechanisms for crosstalk between apoptosis and autophagy mediating heart failure due to doxorubicin therapy. Trial registration(20192BBGL7D031) 2019-09-17.

scholarly journals Ling-Gui-Zhu-Gan Decoction Protects H9c2 Cells against H2O2-Induced Oxidative Injury via Regulation of the Nrf2/Keap1/HO-1 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiang Wang ◽  
Tongjuan Tang ◽  
Mengting Zhai ◽  
Ruirui Ge ◽  
Liang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Stress Response ◽  
Caspase 3 ◽  
Underlying Mechanism ◽  
Oxidative Stress Response ◽  
Control Group ◽  
H9c2 Cells ◽  
Model Group ◽  
Blank Control Group

Objectives. Ling-Gui-Zhu-Gan decoction (LGZGD) is a potentially effective treatment for heart failure, and it showed significant anti-inflammatory potential in our previous studies. However, its ability to ameliorate heart failure through regulation of oxidative stress response is still unknown. This study was aimed to investigate the protective effect of LGZGD-containing serum on H2O2-induced oxidative injury in H9c2 cells and explore the underlying mechanism. Methods. Eighteen rats were randomly divided into two groups: the blank control group and LGZGD group. The LGZGD group rats were administrated with 8.4 g/kg/d LGZGD for seven consecutive days through gavage, while the blank control group rats were given an equal volume of saline. The serum was extracted from all the rats. To investigate the efficacy and the underlying mechanism of LGZGD, we categorized the H9c2 cells into groups: the control group, model group, normal serum control (NSC) group, LGZGD group, LGZGD + all-trans-retinoic acid (ATRA) group, and ATRA group. Malonedialdehyde (MDA) and superoxide dismutase (SOD) were used as markers for oxidative stress. Dichlorodihydrofluorescin diacetate (DCFH-DA) staining was used to measure the levels of reactive oxygen species (ROS). The apoptosis rate was detected using flow cytometry. The expression levels of pro-caspase-3, cleaved-caspase-3, Bcl-2, Bax, Keap1, Nrf2, and HO-1 were measured using western blotting. The mRNA levels of Keap1, Nrf2, and HO-1 were measured using RT-qPCR. Results. The LGZGD attenuated injury to H9c2 cells and reduced the apoptosis rate. It was also found to upregulate the SOD activity and suppress the formation of MDA and ROS. The expression levels of pro-caspase-3 and Bcl-2 were significantly increased, while those of cleaved-caspase-3 and Bax were decreased in the LGZGD group compared with the model group. As compared with the model group, the LGZGD group demonstrated decreased Keap1 protein expression and significantly increased Nrf2 nuclear expression and Nrf2-mediated transcriptional activity. ATRA was found to reverse the LGZGD-mediated antioxidative and antiapoptotic effect on injured H9c2 cells induced by H2O2. Conclusion. Our results demonstrated that LGZGD attenuated the H2O2-induced injury to H9c2 cells by inhibiting oxidative stress and apoptosis via the Nrf2/Keap1/HO-1 pathway. These observations suggest that LGZGD might prevent and treat heart failure through regulation of the oxidative stress response.

scholarly journals Effect of Malus halliana Koehne Polysaccharides on Functional Constipation

2018 ◽  
Vol 16 (1) ◽  
pp. 956-962 ◽  
Author(s):  
Yingying Niu ◽  
Junya Wang ◽  
Pengyu Wang ◽  
Xiuchun Guo ◽  
Jinmei Wang ◽  
...  
Keyword(s):  
Substance P ◽  
Moisture Content ◽  
Dose Group ◽  
Low Dose ◽  
Functional Constipation ◽  
Positive Control ◽  
Positive Control Group ◽  
Control Group ◽  
Group Model ◽  
Model Group

AbstractThe effects of Malus halliana Koehne polysaccharides on functional constipation was investigated in this study. The rats were divided into six groups: normal group, model group, positive control group, M. halliana polysaccharides high dose groups 1200 mg/ kg, medium dose groups 1000 mg/ kg and low dose groups 800 mg/kg. The model of constipation was established by loperamide hydrochloride. Feces weight at 6 and 24 hours after treatment, Colon moisture content, in addition the levels of motilin (MTL), gastrin (Gas), somatostatin (SS), substance P (SP) in serum were used to evaluate the preventive effects of M. halliana polysaccharides on constipation. Compared with the model group, the positive control group, M. halliana polysaccharide high, medium and low dose group 6 h weight of feces, colon moisture content, the levels of motilin (MTL), gastrin (GAS) and substance P(SP) significantly (p <0.01) increased, the levels of somatostatin (SS) significantly decreased. The results indicated that the high, middle and low dosage of M. halliana polysaccharide could effectively improve functional constipation. Amongst these doses, the low dose group was better than others.

The Effects of Moxibustion on Serum Interleukins and T Cell Subset in H.polyri Infected Rats

2015 ◽  
Vol 3 (1) ◽  
pp. 38-45
Author(s):  
Jing Shen ◽  
Yan Peng ◽  
Dong-Mei Shi ◽  
Yin-Shuai Feng ◽  
Yan-Ling Hou ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Control Group ◽  
Intragastric Administration ◽  
Therapeutic Effects ◽  
Model Group ◽  
Tnf Α ◽  
Group A ◽  
Histomorphological Changes ◽  
Group B ◽  
Group D

Abstract Objective: to observe the effects of moxibustion on histomorphological changes of gastric mucosa, as well as on serum IL-6、IL-8、TNF-α，Hp IgG、CD3+、CD4+、CD8+ in helicobacter pylori (Hp) infected rats, so that to better understand how the moxibustion repairs the Hp- induced gastric mucosal injury. Methods: 40 SD rats were randomly assigned to four groups: group A (blank control), group B (Hp infection model), group C (moxibustion plus model), group D (electro-acupuncture plus model), 10 for each group. The “NaHCO3 plus Indometacin and Hp intragastric administration” method was employed to make gastritis model. Acupoints selected for “repair” purpose were Zu San Li (ST36), Zhong Wan (CV12), Guan Yuan (RN4), Pi Shu (BL20), Wei Shu(BL21). The histomorphological changes of gastric mucosa in rats were observed under light microscope after HE stain; IL-6, IL-8, TNF-α, Hp IgG values were evaluated by ELISA method; values of CD3+、CD4+、CD8+、CD4+/CD8+ were measured by flow cytometry method. Results: compared with group A, the values of IL-6, IL-8, TNF-α, Hp IgG and CD8+ in group B were increased（P＜0.01）, whereas the values of CD3+、CD4+、CD4+/CD8+ were decreased（P＜0.01）. Compared with group B, the values of IL-8（P＜0.05）,TNF-α（P＜0.05）, IL-6（P＜0.01）, Hp IgG（P＜0.01） and CD8+ （P＜0.05） in group C were decreased, whereas the values of CD3+（P＜0.05）,CD4+（P＜0.05）,CD4+/CD8+ （P＜0.05） were increased, meanwhile such values in group D had no significant changes. Compared with group D, the values of IL-6（P＜0.05）,IL-8 （P＜0.05）and Hp IgG （P＜0.01）in group C were decreased, whereas CD4+/CD8+（P＜0.05）were increased, all those changes had statistical significance. Conclusion: the preventive and therapeutic effects of moxibustion on Hp related gastritis might be realized by two ways- to inhibit the secretion of proinflammatory cytokines such as IL-6, IL-8 and TNF-α, or to regulate the production of immune factors (such as up-regulation of CD3+, CD4+ and down-regulation of CD8+).

scholarly journals Effects of Yiqi Tongyang on HCN4 Protein Phosphorylation in Damaged Rabbit Sinoatrial Node Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-6
Author(s):  
Jinfeng Liu ◽  
Ruxiu Liu ◽  
Jie Peng ◽  
Yanli Wang
Keyword(s):  
Protein Expression ◽  
Protein Phosphorylation ◽  
Treatment Effects ◽  
Molecular Mechanisms ◽  
Sinoatrial Node ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Model Group ◽  
Sinoatrial Node Cells

The hyperpolarization-activated cyclic nucleotide-gated cation channel (If) is closely associated with sinoatrial node pacing function. The present study aimed to investigate the molecular mechanisms involved in pacing function improvements of damaged sinoatrial node cells and the consequent treatment effects on sick sinus syndrome (SSS) after the use of Yiqi Tongyang. HCN4 channel protein expression and phosphorylation were measured by immunoblotting and fluorescent quantitation. After ischemia-reperfusion injury (model group), the HCN4 protein and the optical density (OD) of the phosphorylated HCN4 protein as well as intracellular PKA activity in the sinoatrial node cells decreased significantly. However, the OD values and PKA activity increased to different degrees after treatment with serum containing different doses of Yiqi Tongyang; in contrast, no significant improvement was seen in the control group compared to the model group. These findings demonstrated that the use of the traditional Chinese medicine Yiqi Tongyang could increase HCN4 protein expression and phosphorylation as well as PKA activity within sinoatrial node cells damaged by ischemia-reperfusion. The HCN4 protein is involved in theIf-related ion channel. Here, we speculated that these effects could be associated with upregulation of HCN4 protein phosphorylation, which consequently improved cell automaticity, increased heart rate, and had treatment effects on SSS.

scholarly journals Dissecting the Roles of the Tuberin Protein in the Subcellular Localization of the G2/M Cyclin, Cyclin B1

2021 ◽  
Author(s):  
Jessica Dare-Shih ◽  
Adam Pillon ◽  
Jackie Fong ◽  
Elizabeth Fidalgo da Silva ◽  
Lisa Porter
Keyword(s):  
Cell Cycle ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Molecular Mechanisms ◽  
Cyclin B1 ◽  
Nuclear Accumulation ◽  
Benign Tumors ◽  
Tsc2 Gene ◽  
Organ Systems ◽  
Wide Range

Tuberin is a major component of the protein regulatory complex known as the Tuberous Sclerosis Complex and plays a crucial role in cell cycle progression and protein synthesis. Mutations in the Tuberin gene, TSC2, lead to the formation of benign tumors in many organ systems and causes the Tuberous Sclerosis Complex disorder. Genotypes ranging from point mutations to large deletions in the TSC2 gene have been clinically characterized with a wide range of phenotypes from skin tumors to large brain tumors. Our current work investigates the molecular mechanisms behind Tuberin and its ability to regulate the cell cycle through its binding to the G2/M cyclin, Cyclin B1. After creating an early stop codon in a critical region of the Tuberin, our results show the in vitro phenotype that occurs from a truncated Tuberin protein. Herein we demonstrate that this clinically relevant truncated form of Tuberin promotes an increased nuclear accumulation of Cyclin B1 and a subsequent increase in cell proliferation supporting the phenotypic data seen in the clinic with Tuberous Sclerosis Complex patients showing deletions within the TSC2 gene. This data provides an insight into some of the functional and molecular consequences of truncated proteins that are seen in clinical patients.

Animal-Assisted Therapy in Patients Hospitalized With Heart Failure

2007 ◽  
Vol 16 (6) ◽  
pp. 575-585 ◽  
Author(s):  
Kathie M. Cole ◽  
Anna Gawlinski ◽  
Neil Steers ◽  
Jenny Kotlerman
Keyword(s):  
Heart Failure ◽  
State Anxiety ◽  
Repeated Measures ◽  
Animal Assisted Therapy ◽  
Control Group ◽  
Systolic Pulmonary Artery Pressure ◽  
Therapy Dog ◽  
Pulmonary Capillary ◽  
Sum Score ◽  
Group A

Background Animal-assisted therapy improves physiological and psychosocial variables in healthy and hypertensive patients. Objectives To determine whether a 12-minute hospital visit with a therapy dog improves hemodynamic measures, lowers neurohormone levels, and decreases state anxiety in patients with advanced heart failure. Methods A 3-group randomized repeated-measures experimental design was used in 76 adults. Longitudinal analysis was used to model differences among the 3 groups at 3 times. One group received a 12-minute visit from a volunteer with a therapy dog; another group, a 12-minute visit from a volunteer; and the control group, usual care. Data were collected at baseline, at 8 minutes, and at 16 minutes. Results Compared with controls, the volunteer-dog group had significantly greater decreases in systolic pulmonary artery pressure during (−4.32 mm Hg, P = .03) and after (−5.78 mm Hg, P = .001) and in pulmonary capillary wedge pressure during (−2.74 mm Hg, P = .01) and after (−4.31 mm Hg, P = .001) the intervention. Compared with the volunteer-only group, the volunteer-dog group had significantly greater decreases in epinephrine levels during (−15.86 pg/mL, P = .04) and after (−17.54 pg/mL, P = .04) and in norepinephrine levels during (−232.36 pg/mL, P = .02) and after (−240.14 pg/mL, P = .02) the intervention. After the intervention, the volunteer-dog group had the greatest decrease from baseline in state anxiety sum score compared with the volunteer-only (−6.65 units, P =.002) and the control groups (−9.13 units, P &lt; .001). Conclusions Animal-assisted therapy improves cardiopulmonary pressures, neurohormone levels, and anxiety in patients hospitalized with heart failure.

scholarly journals The Effect of Acupuncture to SP6 on Skin Temperature Changes of SP6 and SP10: An Observation of “Deqi”

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jia-Min Yang ◽  
Xiao-Yu Shen ◽  
Ling Zhang ◽  
Song-Xi Shen ◽  
Dan-Dan Qi ◽  
...  
Keyword(s):  
Skin Temperature ◽  
Saline Control ◽  
Control Group ◽  
Group Model ◽  
Model Group ◽  
Saline Control Group ◽  
Temperature Changes ◽  
Group A ◽  
Group B ◽  
The Relationship

Background. Deqi sensation is a complex but an important component for acupuncture effect. In this study, we tried to observe the relationship between Deqi and skin temperature changes and whether there was some relativity between Deqi and needle stimulations on cold congealing and dysmenorrhea rat model. Thirty-two female Sprague Dawley (SD) rats were randomly divided into four groups (Saline Control Group, Model Group, Group A with strong stimulation, and Group B with small stimulation). Group A and Group B were performed with different stimulations. We found that, compared with saline control group, model group, and Group B, Group A showed that the skin temperature changes on right acupoint SP6 and SP10 increased significantly at 5 min–10 min interval. The skin temperature changes on left SP6 decreased at instant–5 min interval. The skin temperature changes on right SP10 decreased significantly at instant–5 min interval and 10 min–20 min interval. Thermogenic action along Spleen Meridian of Foot Greater Yin was manifested as simultaneous skin temperature increase on right SP6 and SP10 at 5 min–10 min interval after needling SP6, which was helpful to illustrate the relationship between the characteristic of Deqi and needle stimulations.

P323Triage-HF Plus: identification of heart failure and non-heart failure events in an ambulatory population using remote monitoring and the triage heart failure risk score Algorithm

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
F Ahmed ◽  
J Taylor ◽  
C Green ◽  
L Wickwar ◽  
A Zaidi ◽  
...  
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Risk Score ◽  
Remote Monitoring ◽  
Predictive Value ◽  
Control Group ◽  
Telephone Triage ◽  
Integrated Monitoring ◽  
Failure Risk ◽  
Wide Range

Abstract Background/introduction Previous studies examining the utility of cardiac implantable electronic devices (CIEDs) to remotely monitor heart failure patients for decompensation have not demonstrated an impact on hard end-points. However, a key limitation of these prior studies (REM-HF and MORE-CARE) has been the failure to stratify patients according to their risk of worsening heart failure (WHF) prior to randomization (usual care vs active monitoring). We examined a different approach, using a single manufacturer’s remote monitoring platform, whereby only patients with CIED-derived data indicating the highest risk of WHF are contacted for assessment. The validated ‘Triage Heart Failure Risk Score’ (Triage-HFRS) is a medical algorithm within Medtronic CIEDs that can risk-stratify patients as low-, medium- or high-risk of WHF in the next 30 days based on integrated monitoring of physiological parameters. Purpose  This study is the largest prospective evaluation of the Triage-HFRS, and examines the additional role of contacting those patients with a ‘High-Risk’ Triage-HFRS alert by telephone (Triage-HF Plus pathway). Methods  Prospective, real-world evaluation of the Triage-HF Plus pathway undertaken between June 2016 and September 2019. 326 high-risk Triage-HFRS transmissions were contacted for telephone triage assessment. Screening questions were designed to identify episodes of WHF and non-heart failure events. Interventions were at the discretion of the clinical practitioner and in line with guideline-directed practice. An additional 3-month consecutive sample of low and medium Triage-HFRS transmissions (control group) were also contacted for telephone triage assessment (n= 98). Results Successful telephone contact was made following 245 high-risk Triage-HFRS alerts. Following contact, 194 (79.1%) patients reported an acute medical issue: 137 (70.6%) reported symptoms consistent with worsening heart failure (WHF) requiring intervention; and 57 (29.4%) had an alternative acute medical problem. 51 (26.2%) had no apparent reason for the high score. The sensitivity and specificity of CIED-based remote monitoring to identify any HF and non-HF events requiring intervention was 99.5% (97.2-99.9%) and 65.5% (57.3-73.2%) respectively; positive predictive value was 79.2%. The negative predictive value of a non-high risk score to rule out an acute event was 98.9%. Overall accuracy of the pathway to identify an acute issue (HF or non-HF related) was 84.8%. Conclusion The Triage-HF Plus clinical pathway is a potentially useful remote monitoring tool for patients with heart failure. The pathway has high diagnostic accuracy to identify patients with WHF and a wide range of non-HF issues which are just as relevant in a population who often have multiple complex co-morbidities and are known for their high health care utilisation.

scholarly journals The Roles of Skin Fibroblasts at Local Acupoints in Chrono-Acupuncture

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nannan Liu ◽  
Zhengyu Zhao ◽  
Qizhi Zhou ◽  
Xiaohong Zhang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Acupuncture Treatment ◽  
Treatment Time ◽  
Subcutaneous Tissue ◽  
Acupuncture Group ◽  
Control Group ◽  
Model Group ◽  
Time Points ◽  
Group A ◽  
And Control ◽  
Time Point

Objective. The aim of this study was to demonstrate the peripheral mechanisms of chrono-acupuncture by observing acupuncture at different time points affecting relative proteins to regulate the cytoskeleton of fibroblasts differently. Methods. A total of 108 male SD rats (180–220 g) that have basic pain threshold within 3–10 s were selected and randomly divided into group A (n = 72) and control group (n = 36). After the succession of modeling with CFA injection, the rats in group A were randomly divided into model group and acupuncture group, each group containing 36 rats. Then according to the different treatment time, each group was randomly classified into 6 subgroups (ZT0, ZT4, ZT8, ZT12, ZT16, and ZT20), each subgroup containing 6 rats (n = 6). On the second day of successful modeling, the rats in the acupuncture group received acupuncture treatment at the corresponding time point, while the control group and the model group were only tied up at the corresponding time point without any treatments. Methods of operation: use 0.5-inch needles, puncture the rats’ “Zusanli” on the affected limb, with Twirling manipulation for a minute after every five minutes; the treatment lasts thirty minutes in total. After 7 days of treatments, the skin and subcutaneous tissue of rats’ acupoint area of “Zusanli” on the affected limb were taken and then stained by immunofluorescence double staining method to observe the expression of the fibroblast cytoskeleton F-actin and β-tubulin under the LSCM while using western blot to observe the expression of P38MAPK/P-P38MAPK. Results. The expression of the cytoskeleton F-actin and β-tubulin at acupoint area in the acupuncture group was significantly higher than that in the control and model group. The effect of acupuncture on the restructure of the fibroblast cytoskeleton is different at different time points, the most effective time point was at ZT12 while the least at ZT16. Acupuncture can decrease the high expression of P-P38MAPK/P38MAPK in the model group, and the effect has time differences. The expression of P-P38MAPK/P38MAPK increased more significantly at ZT16 than ZT12. Conclusion. The remodeling difference of fibroblast cytoskeleton after receiving acupuncture treatment could be one of the peripheral bases of the chrono-acupuncture.

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