1.Mechanism of Naoxintong Capsules Against Ischemia-reperfusion Injury in Rats via Inhibiting Pericyte Contraction Based on RHOA/ROCK1 Pathway
Yinlian WEN ; Jinfeng SHANG ; Bohong WANG ; Wanting WEI ; Xiaolu ZHANG ; Guijinfeng HUANG ; Xin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):159-167
ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion (I/R) injury in rats based on the changes of pericytes mediated by Ras homolog family member A (RHOA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) pathway. MethodsNinety rats (15 rats for each group) were randomly divided into a sham operation group, a model group, a positive control group receiving Ginkgo biloba extract (21.6 mg·kg-1), and groups receiving Naoxintong capsules at low, medium, and high doses of 55, 110, and 220 mg·kg-1 (NXT-L, NXT-M, and NXT-H groups), respectively. Except for those in the sham operation group, all rats were subjected to transient middle cerebral artery occlusion (tMCAO) to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager, and the cerebral infarction rate was calculated using 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. Pathological changes were observed by hematoxylin-eosin (HE) staining and Nissl staining, while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression levels of RHOA, ROCK1, platelet-derived growth factor receptor β (PDGFRB), α-smooth muscle actin (α-SMA), tight junction protein (ZO-1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). ResultsCompared with the sham operation group, the model group exhibited decreased neurological function scores, higher percentage reduction in blood flow, and increased cerebral infarction rates (P<0.01). Additionally, cortical neuronal nucleus shrinkage, edema, a decreased number of Nissl bodies, reduced pericyte area, elevated albumin content in the cortex (P<0.05), and increased ischemic modified albumin levels (P<0.01) were observed. The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were increased (P<0.01), while those of ZO-1 were decreased. Compared with the model group, all treatment groups showed improved neurological function scores, lower percentage reduction in blood flow, reduced cerebral infarction rates (P<0.01), alleviated cortical histological changes, increased number of Nissl bodies, expanded pericyte area, decreased albumin content in the cortex, and reduced ischemia-modified albumin levels (P<0.01). The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were decreased (P<0.01), while those of ZO-1 were increased. Among the treatment groups, the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply, reduce microcirculation disturbance, and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.
2.Mechanism of Naoxintong Capsules Against Ischemia-reperfusion Injury in Rats via Inhibiting Pericyte Contraction Based on RHOA/ROCK1 Pathway
Yinlian WEN ; Jinfeng SHANG ; Bohong WANG ; Wanting WEI ; Xiaolu ZHANG ; Guijinfeng HUANG ; Xin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):159-167
ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion (I/R) injury in rats based on the changes of pericytes mediated by Ras homolog family member A (RHOA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) pathway. MethodsNinety rats (15 rats for each group) were randomly divided into a sham operation group, a model group, a positive control group receiving Ginkgo biloba extract (21.6 mg·kg-1), and groups receiving Naoxintong capsules at low, medium, and high doses of 55, 110, and 220 mg·kg-1 (NXT-L, NXT-M, and NXT-H groups), respectively. Except for those in the sham operation group, all rats were subjected to transient middle cerebral artery occlusion (tMCAO) to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager, and the cerebral infarction rate was calculated using 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. Pathological changes were observed by hematoxylin-eosin (HE) staining and Nissl staining, while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression levels of RHOA, ROCK1, platelet-derived growth factor receptor β (PDGFRB), α-smooth muscle actin (α-SMA), tight junction protein (ZO-1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). ResultsCompared with the sham operation group, the model group exhibited decreased neurological function scores, higher percentage reduction in blood flow, and increased cerebral infarction rates (P<0.01). Additionally, cortical neuronal nucleus shrinkage, edema, a decreased number of Nissl bodies, reduced pericyte area, elevated albumin content in the cortex (P<0.05), and increased ischemic modified albumin levels (P<0.01) were observed. The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were increased (P<0.01), while those of ZO-1 were decreased. Compared with the model group, all treatment groups showed improved neurological function scores, lower percentage reduction in blood flow, reduced cerebral infarction rates (P<0.01), alleviated cortical histological changes, increased number of Nissl bodies, expanded pericyte area, decreased albumin content in the cortex, and reduced ischemia-modified albumin levels (P<0.01). The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were decreased (P<0.01), while those of ZO-1 were increased. Among the treatment groups, the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply, reduce microcirculation disturbance, and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.
3.Effect of Sinisan on Oxidative Stress in Cholestatic Hepatitis Rats Based on Nrf2/HO-1 Signaling Pathway
Dan CAO ; Qi CHEN ; Xiaolu CHEN ; Linzhen CHEN ; Haiyan WANG ; Juhui HAO ; Wei ZHANG ; Zhiqiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):1-7
ObjectiveBased on the nuclear factor erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway, this paper explores the effect of Sinisan (SNS) on liver oxidative stress injury in cholestatic hepatitis rats and its mechanism. MethodThirty 6-week-old male SD rats were randomly divided into a control group, model group, low and high dose groups of SNS (2.5 and 5 g·kg-1) and ursodeoxycholic acid group (UDCA, 63 mg·kg-1), with six rats in each group. Rats were administrated for seven consecutive days. On the 5th day, the control group was given olive oil of 10 mL·kg-1, and the other groups were given alpha-naphthalene isothiocyanate (ANIT) of 80 mg·kg-1. The serum biochemical indicator levels of cholestasis and the content of antioxidant factors in rat liver were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes in liver tissue. The relative mRNA and protein expressions of Nrf2, HO-1, and quinone oxidoreductase 1 (NQO1) in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultCompared with the control group, the model group showed a significant increase in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue (P<0.01). There were obvious pathological changes in the model group such as the disordered arrangement of hepatocytes, obvious congestion and necrosis in the portal area, infiltration of inflammatory cells, and destruction of the interlobular bile duct. The relative mRNA and protein expressions of Nrf2, HO-1, and NQO1 in liver tissue were significantly down-regulated in the model group (P<0.05, P<0.01). Compared with the model group, the groups of SNS showed a significant decrease in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue (P<0.01), and the pathological liver injury was obviously improved. The necrotic area was reduced, and the infiltration of inflammatory cells was decreased. In addition, there was a small amount of extravasated blood in the interlobular vein. The relative mRNA and protein expressions of Nrf2, HO-1, and NQO1 in liver tissue were significantly up-regulated (P<0.05, P<0.01). ConclusionSNS can significantly improve liver injury in cholestatic hepatitis rats, and its mechanism may be related to the inhibition of oxidative stress response mediated by the Nrf2/HO-1 signaling pathway.
4.The Effect of Puerarin in Alleviating Myocardial Ischemia-reperfusion Injury in Rats Based on Molecular Docking and Molecular Dynamics Simulation
Chunyan ZHANG ; Xiaolu CAO ; Song LIU
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2024;53(1):26-32
Objective To investigate the effects of puerarin on myocardial ischemia-reperfusion injury and its mecha-nism.Methods Molecular docking and dynamics simulation were utilized to predict the binding potential of puerarin and SIRT1.A myocardial ischemia-reperfusion model was established in SD rats by ligating the anterior descending branch of the left coronary artery.The protective effect of puerarin on myocardial injury was observed,and the therapeutic effect of puerarin was compared after inhibition of SIRT1 expression.The infarct volume was detected using 2,3,5-triphenyltetrazolium chloride(TTC)staining.The apoptosis rate and SIRT1 expression of cardiomyocytes were detected by using TUNEL combined with im-munofluorescence.Transmission electron microscope was used to observe the myocardial ultrastructure.Western blot was per-formed to detect the expression of ferroptosis-related proteins.Results Molecular docking studies confirmed the formation of stable complexes between puerarin and SIRT1.Puerarin treatment significantly increased myocardial ischemia-reperfusion injury through upregulation of SIRT1,SLC7A11 and GPX4 expression,and downregulation of IREB2 expression in rats.The protec-tive effect of puerarin on myocardium was abolished once SIRT1 protein expression was inhibited.Conclusion Molecular doc-king and molecular dynamics simulation techniques can accurately predict the interaction of puerarin,and the main target SIRT1.Puerarin inhibits ferroptosis by activating SIRT1 pathway,thereby alleviating myocardial ischemia-reperfusion injury.
5.Application evaluation of cardiopulmonary exercise test to guide comprehensive pulmonary rehabilitation in patients with pneumoconiosis
Congxia YAN ; Baoping LI ; Fuhai SHEN ; Hong CAO ; Jing LI ; Lirong ZHANG ; Zhiping SUN ; Bowen HOU ; Lini GAO ; Xinyu LI ; Chaoyi MA ; Xiaolu LIU
Journal of Environmental and Occupational Medicine 2024;41(1):47-53
Background At present, the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage. The basis for formulating an individualized comprehensive pulmonary rehabilitation plan is still insufficient, which is one of the factors limiting the development of community-level rehabilitation work. Objective To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test (CPET), conduct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumoconiosis, and evaluate its role in improving exercise endurance and quality of life, thus provide a basis for the application and promotion of pulmonary rehabilitation. Methods A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co., Ltd. from April to August 2022 , and were divided into an intervention group and a control group by random number table method, with 34 cases in each group. All the pneumoconiosis patients participated in a baseline test. The control group was given routine drug treatment, while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment, including health education, breathing training, exercise training, nutrition guidance, psychological intervention, and sleep management, whose exercise intensity was determined according to the maximum heart rate provided by CPET. The rehabilitation training lasted for 24 weeks. Patients were evaluated at registration and the end of study respectively. CPET was used to measure peak oxygen uptake per kilogram (pVO2/kg), anaerobic threshold (AT), carbon dioxide equivalent of ventilation (EqCO2), maximum metabolic equivalent (METs), and maximum work (Wmax). The modified British Medical Research Council Dyspnea Questionnaire (mMRC), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Short Form of Health Survey (SF-36) were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. Results Among the included 68 patients, 63 patients were having complete data, then 31 cases were assigned in the control group and 32 cases in the interventional group. Before the intervention, there was no significant difference in pVO2/kg, AT, EqCO2, METs, or Wmax between the two groups (P>0.05). At the end of the trail, the indicators like pVO2/kg [(19.81±2.38) mL·(min·kg)−1], AT [(14.48±2.33) mL·(min·kg)−1], METs (5.64±0.69), and Wmax [(85.25±14) W] of patients in the intervention group were all higher than those [(13.90±2.37) mL·(min·kg)−1, (11.70±1.94) mL·(min kg)−1, (3.97±0.70), and (61.77±14.72) W, respectively] in the control group (P<0.001); there was no significant difference in EqCO2 between the two groups (P=0.083). Before the trial, there was no significant difference in mMRC, SAS, SDS, PSQI, or CAT scores between the two groups (P>0.05). At the end of the trail, the mMRC score (1.16±0.57), SAS score (27.93±2.12), SDS score (26.48±1.44), PSQI score (1.08±0.88), and CAT score (4.34±3.28) of patients in the intervention group were lower than those [(2.03±0.83), (35.87±6.91), (34.23±6.65), (5.37±3.03), and (13.87±7.53), respectively] in the control group (P<0.001). The SF-36 scores of bodily pain (94.13±10.72), general health (87.50±5.68), vitality (95.31±5.53), mental health (99.88±0.71), and health changes (74.22±4.42) in the intervention group were higher than those [(71.87±32.72), (65.81±15.55), (74.52±16.45), (86.97±16.56), and (29.84±13.50), respectively] in the control group (P<0.001), and no significant difference was found in social functioning and role emotional scores (P>0.05). Conclusion Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients, ameliorate dyspnea symptoms, elevate psychological state and sleep quality, and improve the quality of life.
6.Study on the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis
Rong JIN ; Xiaolu ZHAO ; Yuxin YAN ; Xiaoyang GAO ; Chunyan ZHANG ; Mingqi LI ; Yuehong MA
China Pharmacy 2024;35(3):277-282
OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis (HF). METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the pathological changes in liver tissue, mRNA and protein expressions of HF indexes [α-smooth muscle actin (α-SMA), collagen type Ⅰ] and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway-related factors were detected, and the improvement effects and possible mechanism of low-dose, medium-dose and high-dose (50, 100, 200 mg/kg) of alcoholic extract from S. comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic extract from S. comosa at a concentration of 1 800 mg/(kg·d) (calculated by the amount of raw material). The effects of drug- containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of HSC-T6 cells with low, medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa (diluted to 10%, 15%, 20%). miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells, and the mRNA and protein expressions of factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low, medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of HF rats, and the percentage of collagen was significantly reduced (P<0.01); mRNA and protein expressions of the indicators related to HF as well as PI3K and Akt were significantly reduced (P<0.01), and mRNA and protein expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN) were increased in liver tissue of rats (P<0.01). The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S. comosa significantly inhibited the expression of miRNA-21 at low, medium and high concentrations (P<0.01); whereas after transfection with miRNA-21 mimics, it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt (P<0.01), while significantly decreased mRNA and protein expressions of PTEN (P<0.01); after transfection with miRNA-21 inhibitor, the changes of above indexes were opposite to the above results (P<0.01). CONCLUSIONS Alcoholic extracts of S. comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21, so as to achieve the effect of anti-hepatic fibrosis.
7.In vitro oral simulation evaluation of palatability and chewability of chewable tablets
Aonan ZHONG ; Conghui LI ; Zengming WANG ; Xiaolu HAN ; Hui ZHANG ; Nan LIU ; He ZHANG ; Jintao LIN ; Chunyan LIU ; Aiping ZHENG
China Pharmacy 2024;35(14):1708-1714
OBJECTIVE To evaluate the palatability and chewability of chewable tablets, and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug, the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer, and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets; the rheometer was adopted to measure the viscoelasticity, thixotropy, and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit, principal component content, and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions, and the force required for chewing was within the range of the chewing force of the teeth; chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue, and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing; when chewing with teeth, the internal force of the chewing tablets decreased, causing plastic deformation and crushing. After being crushed, the shape couldn’t be restored, making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.
8.Chinese-style Comprehensive and Full-Cycle Health Service System:Modernisation Connotations,Characteristics and Pathways
Shouwen ZHANG ; Yuesheng LIAO ; Xiaolu FENG
Chinese Health Economics 2024;43(9):1-5
The modernisation of Chinese-style all-round and full-cycle health service system is an important guarantee to meet the growing health needs of the residents,and it is also a necessary way to promote the construction of a healthy China and achieve universal health coverage.Through literature and logical analysis and other research methods,on the basis of analysing the connotation and characteristics of the modernisation of the Chinese-style comprehensive and full-cycle health service system,the following optimisation progression is proposed:(1)policy leadership-constructing a comprehensive policy system and building a solid health cornerstone;(2)science and technology empowerment-strengthening the application of scientific and technological innovation to drive the development of health;(3)service upgrading-improving the quality of the service process to optimize the health experience;(4)conceptual innovation-changing the traditional concept of health and improving health literacy.
9.Chinese-style Comprehensive and Full-Cycle Health Service System:Modernisation Connotations,Characteristics and Pathways
Shouwen ZHANG ; Yuesheng LIAO ; Xiaolu FENG
Chinese Health Economics 2024;43(9):1-5
The modernisation of Chinese-style all-round and full-cycle health service system is an important guarantee to meet the growing health needs of the residents,and it is also a necessary way to promote the construction of a healthy China and achieve universal health coverage.Through literature and logical analysis and other research methods,on the basis of analysing the connotation and characteristics of the modernisation of the Chinese-style comprehensive and full-cycle health service system,the following optimisation progression is proposed:(1)policy leadership-constructing a comprehensive policy system and building a solid health cornerstone;(2)science and technology empowerment-strengthening the application of scientific and technological innovation to drive the development of health;(3)service upgrading-improving the quality of the service process to optimize the health experience;(4)conceptual innovation-changing the traditional concept of health and improving health literacy.
10.Chinese-style Comprehensive and Full-Cycle Health Service System:Modernisation Connotations,Characteristics and Pathways
Shouwen ZHANG ; Yuesheng LIAO ; Xiaolu FENG
Chinese Health Economics 2024;43(9):1-5
The modernisation of Chinese-style all-round and full-cycle health service system is an important guarantee to meet the growing health needs of the residents,and it is also a necessary way to promote the construction of a healthy China and achieve universal health coverage.Through literature and logical analysis and other research methods,on the basis of analysing the connotation and characteristics of the modernisation of the Chinese-style comprehensive and full-cycle health service system,the following optimisation progression is proposed:(1)policy leadership-constructing a comprehensive policy system and building a solid health cornerstone;(2)science and technology empowerment-strengthening the application of scientific and technological innovation to drive the development of health;(3)service upgrading-improving the quality of the service process to optimize the health experience;(4)conceptual innovation-changing the traditional concept of health and improving health literacy.

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