RESUMO
ObjectiveTo establish a mouse model of basilar artery dolichoectasia （BAD） and explore the mechanism of modified Tongqiao Huoxuetang （JTQHX） in regulating BAD via phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSixty C57/BL6 female mice were randomized into sham operation （injected with 10 U·mL-1 inactivate elastase）， model， atorvastatin calcium tablets （2.6 mg·kg·d-1）， and low- and high-dose （crude drug 3.4， 17 g·kg-1·d-1， respectively） JTQHX groups. The mouse model of BAD was established by injection with 10 U·mL-1 elastase. After 14 days of modeling， the sham operation group and model group were administrated with equal volumes of pure water by gavage， and other groups with corresponding drugs for 2 months. The levels of interleukin-6 （IL-6） and calpain （LpA） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Verhoeff 's Van Gieson （EVG） staining was employed to observe the pathological changes of blood vessels. Terminal-deoxynucleotidyl transferase mediated nick end labeling （TUNEL） was employed to examine the apoptosis rate of vascular smooth muscle cells （VSMCs）. Image Pro Plus was used to observe and calculate the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle of the basilar artery vessels in mice. Western blot was employed to determine the expression levels of PI3K and Akt in the vascular tissue. ResultCompared with the sham operation group， the model group showed lowered IL-6 level （P<0.01）， no significant change in LpA level， increased apoptosis of VSMCs （P<0.01）， and increased curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.01）. Furthermore， the modeling up-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01） and aggravated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. Compared with the model group， 2 months of treatment with JTQHX elevated the IL-6 level （P<0.01）， reduced the apoptosis of VSMCs （P<0.01）， decreased the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.05， P<0.01）， and down-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01）. In addition， the treatment alleviated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. ConclusionJTQHX inhibits the elongation， expansion， and curvature of basilar artery vessels and alleviates the pathological changes by reducing the apoptosis of VSMCs and down-regulating the expression of PI3K/Akt pathway.
RESUMO
Parkinson's disease （PD） is a common neurological degenerative disease in the middle-aged and elderly， characterized by pathological changes of progressive degeneration of dopaminergic neurons in the substantia nigra and Lewy body formation， with high prevalence and long course of disease. The drug is mainly used to treat PD in western medicine， and the early curative effect is remarkable. However， with the progression of the disease and the long-term use of the drug， the efficacy will be significantly reduced， or there may be sports complications， and the long-term efficacy is not good. As a traditional medical system， traditional Chinese medicine has a unique understanding of PD. Traditional Chinese medicine plays an important role in the treatment of PD， which is natural， mild， safe， and effective， and it can cooperate with western medicine to enhance its efficacy and reduce the adverse reactions of western medicine. The pathogenesis of PD is complex， involving multiple levels such as mitochondrial dysfunction and apoptosis. Neuroinflammation is also involved in the progressive degeneration of dopaminergic neurons in PD. The Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway is a classic inflammatory pathway， and its expression changes play an important role in the occurrence and development of inflammatory response in the body. In recent years， the research on this pathway in TCM is increasing. This paper summarized the literature of traditional Chinese and western medicine in the past 10 years and reviewed the relevant mechanism of TCM regulation of TLR4/NF-κB pathway in the treatment of PD from the aspects of TCM monomer， compound， and other TCM therapies， so as to provide some references for the search for new targets of drug therapy and gene therapy and the in-depth study of TCM prevention and treatment of PD.
RESUMO
ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg-1） group， and low- and high-dose （8.4 and 33.6 g·kg-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.
RESUMO
Cerebral ischemia/reperfusion injury （CIRI） is a complex cascade reaction process in which the blood flow and oxygen supply of brain tissue in the infarcted area recover after cerebral ischemia， resulting in secondary injury of ischemic brain tissue. At present， thrombolysis as soon as possible and restoration of cerebral blood supply are still the only strategies for the treatment of stroke， but a considerable number of patients' symptoms will be more serious after reperfusion， making patients face adverse outcomes such as neurological function injury and even death and seriously affecting the quality of life and safety of patients. Therefore， an in-depth exploration of the mechanism and treatment strategy of CIRI has important clinical significance. The phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway is one of the classic anti-apoptosis/reproductive-promoting signal transduction pathways， which is responsible for cell proliferation， growth， and differentiation. It is the key cascade signaling pathway of CIRI， located at the core site in many mechanisms such as mitochondrial disorder， apoptosis， autophagy， oxidative stress， and inflammation. It is closely related to the occurrence and development of CIRI. Traditional Chinese medicine has been used in the clinical treatment of stroke and its complications for thousands of years， and the clinical effect of traditional Chinese medicine in the prevention and treatment of CIRI has been affirmed by a large number of research results in recent years. It is further clarified that the monomers， active components， and their compound prescriptions of traditional Chinese medicine can directly or indirectly regulate the PI3K/Akt signaling pathway by virtue of the biological advantages of multi-targets， multi-components， and multi-pathways and play an overall protective role in CIRI. By analyzing the related research progress of traditional Chinese medicine in China and abroad in recent years， the authors summarized the role and mechanism of regulating the PI3K/Akt signaling pathway in the prevention and treatment of CIRI， so as to provide further theoretical basis for the study of the mechanism of clinical prevention and treatment of CIRI.
RESUMO
Alzheimer's disease （AD） is a neurodegenerative disease associated with aging and age-related cognitive decline. It is characterized by insidious onset and progressive development， and has become a major global health and socioeconomic issue. The exact mechanisms underlying AD have not been fully elucidated， and various hypotheses have been proposed by researchers based on different etiologies， including the amyloid β （Aβ） cascade hypothesis， Tau protein hyperphosphorylation hypothesis， mitochondrial dysfunction and oxidative stress hypothesis， and neurotransmitter hypothesis. Therefore， there is an urgent need for comprehensive interventions targeting multiple pathways， links， and targets. Based on traditional Chinese medicine （TCM） theory and modern research findings， kidney-tonifying and anti-aging Chinese medicines have unique advantages of toxicity reduction， long-lasting effects， and treating both the root cause and the symptoms. They have been shown to counteract immune-inflammatory responses， clear reactive oxygen species， exhibit antioxidant properties， inhibit abnormal aggregation of Aβ and Tau proteins， reduce neuronal apoptosis， regulate central neurotransmitters， and modulate gut microbiota in AD. In recent years， stem cell therapy has been explored for the treatment of AD through two strategies： endogenous activation and exogenous transplantation， thereby replenishing and replacing damaged neurons. However， factors such as blood-brain barrier permeability， targeted delivery to the affected area， immune rejection， and cell survival rate can affect the efficacy of stem cell transplantation. Therefore， combining stem cell therapy with medication and other methods can further enhance the effectiveness of stem cell transplantation. Kidney-tonifying and anti-aging Chinese medicines can activate dormant neural stem cells（NSCs） in the body， promote neuroregeneration， and facilitate tissue and organ repair and reconstruction in AD. The combined treatment of these Chinese medicines and stem cell transplantation has shown more significant efficacy compared to either treatment alone. This combination therapy provides a new integration point for the modernization of TCM and offers new ideas and approaches for the prevention and treatment of AD， as well as improving the effectiveness of stem cell transplantation.
RESUMO
Stroke is one of the major diseases threatening human health， with ischemic stroke accounting for about 70%. Ischemic stroke is characterized by complex pathological mechanism and high incidence， mobility and mortality. At present， the effective clinical treatment measures for ischemic stroke are limited， and it is urgent to develop new and effective treatment measures to improve the prognosis of patients. In recent years， bone marrow mesenchymal stem cells （BMSCs） transplantation has shown great therapeutic potential for a variety of diseases， including ischemic stroke， and has become a new research hotspot. However， due to the low homing and survival rate of BMSCs in human body after transplantation， their clinical effect on ischemic stroke needs to be further improved. With the characteristics of multi-components， multi-channels and multi-targets， Chinese medicine displays desirable curative effect on ischemic stroke， which has been widely concerned. Both Chinese medicine and BMSCs transplantation have good overall brain protection， and their combined effect on ischemic stroke is significantly better than that of single application. The mechanisms include improving the transplantation efficiency of BMSCs， promoting angiogenesis， enhancing neuroplasticity， ameliorating neuroinflammation， enhancing neuroprotection， and regulating the blood-brain barrier and exosomes. The combination of Chinese medicine and modern cutting-edge cell therapy reflects the advantages of integrative medicine， providing a new model and idea for preventing and treating ischemic stroke and improving the efficacy of BMSCs transplantation.
RESUMO
Objective:To investigate the effect of magnetic resonance angiography (MRA) in evaluating the mouse model of vertebrobasilar dolichoectasia (VBD) induced by injection of elastase into cerebellomedullary cistern.Methods:Twenty-four male C57/BL6 mice were selected. The mice in the elastase group ( n=12) were injected in the cerebellomedullary cistern with 2.5 μl of phosphate buffer containing 25 mU elastase, and the mice in the saline control group ( n=12) were injected with the same volume of normal saline. MRA examination of the brains of living mice was performed 2 weeks after modeling. Successful modeling was defined as the basilar artery bending angle ≤170°, or the basilar artery bending length accounts for ≥10%, or the basilar artery deviated from the midline by more than 1 grade, or the percentage increase in artery diameter was ≥25%. Results:In the elastase group and the saline control group, 2 mice and 1 mouse did not wake up normally or died, respectively. The 11 surviving mice in the saline control group had no obvious vertebral artery and basilar artery abnormalities. The success rate of modeling in the 10 surviving mice in the elastase group was 80%, and the difference in the success rate between the two groups was statistically significant ( P<0.05). There were significant differences in mean basilar artery diameter (0.30 mm vs. 0.22 mm; P<0.05), mean basilar artery bending angle (115° vs. 170°; P<0.05), and proportion of mean basilar artery bending length (31% vs. 5%; P<0.05) of the surviving mice between the elastase group and the saline control group. Conclusion:MRA can better evaluate the mouse VBD model induced by elastase injection in the cerebellomedullary cistern.
RESUMO
Posterior circulation ischemic stroke can be manifested as isolated vertigo, and the posterior circulation small infarcts often show early negative diffusion-weighted imaging, which is likely to cause misdiagnosis and missed diagnosis. Summarizing the characteristics and screening strategies of these patients can provide help for timely diagnosis and selection of effective treatment strategies.
RESUMO
Objective To observe the clinical effect of Xiaoke-Yuzu decoction on diabetic peripheral neuropathy (DPN). Methods A total of 100 DPN inpatients were recruited and randomly divided into the treatment and control groups. The two groups were both received basic therapy, while the treatment group additionally received Xiaoke-Yuzu decoction. Toronto clinical scores and Chinese medicine symptom scores of both groups were collected to evaluate the clinical effect before and after the therapy. Results The Toronto scores of treatment group were significantly lower than control group after treatment (symptoms score 1.50 ± 0.94 vs. 2.23 ± 1.01, reflection score 3.60 ± 1.77 vs. 4.27 ± 1.72, feeling test score 1.53 ± 0.63 vs. 2.10 ± 0.84,all P<0.05). Meanwhile, the Chinese medicine symptom scores of treatment group were also significantly lower than the control group (main symptom score 1.77 ± 1.17 vs. 3.17 ± 1.82, posterior symptom score 2.23 ± 1.59 vs. 4.27 ± 1.57, the tongue and pulse score 1.83 ± 0.65 vs. 2.47 ± 0.51, all P<0.05). Conclusion Xiaoke-Yuzu decoction plus basic therpy could improve the clinical symptoms of DPN patients.