Zang-Xiang theory is one of the core theories of basic theory of traditional Chinese medicine, mainly based on the theory of Yinyang and Five elements. The theory of Yinyang and Five elements has its inherent limitations and unreasonable elements. The development of Zang-Xiang theory, to fully absorb the fruits of modern science and technology development, so that the theory of Zang-Xiang continue to improve and improve. Brain for the God of the body, regulating the function of internal organs, balance yin and yang, coordination of blood running fluid. Although the Zang-Xiang theory that the heart for the monarch of the official, the internal organs of the physiological function of the dominant role. However, in the highly developed science and technology today, we should re-examine this theory, combing and development of traditional Chinese medicine theory, to better integrate with the results of contemporary scientific development, to better guide the clinical practice of Chinese medicine.

[Objective]To investigate the protective effect of Zhuangtongyin on the Middle Cerebral Artery Occlusion(MCAO)model by modulating ferroptosis through the Nrf2-SCL7A11/xCT-Gpx4 pathway and its underlying mechanism.[Methods]C57BL/6J mice were randomly divided into Sham operation group(Sham),model group(MCAO),low-dose Zhuangtongyin group(ZTY-L),high-dose Zhuangtongyin group(ZTY-H),with 5 mice in each group.The MCAO group was modelled by silica gel embolization,the middle cerebral artery of mice was embolized for 1h,then the silica gel was pulled out and reperfusion was performed after 72 h;and the other operations in the Sham group were the same as those in the MCAO group except that the thread plug was not inserted.The neural function of mice was evaluated by Zea-Longa method.TTC staining was used to evaluate the volume of cerebral infarction.The level of brain injury was evaluated by HE staining and Nissl staining.Prussian blue staining and the expression of iron transport-related carrier receptors TfR1 and DMT1 on mRNA level was detected by qPCR to evaluate the iron ion deposition level in mice brain.The expression of lipid peroxidation-related gene ACSL4 on mRNA level was detected by qPCR,and the content of 4-HNE was detected by ELISA kit to evaluate the lipid peroxidation level of mice brain.The expressions of ferroptosis marker PTGS2 mRNA level was detected by qPCR.The expressions of Nrf2,SCL7A11/xCT,Gpx4 in mice brain tissue were detected by Western-blot and immunofluorescence.[Results]Zhuangtongyin improved the nerve function of mice after MCAO(P＜0.05)and the cerebral infarction volume of mice(P＜0.05)and alleviate the pathological injury of cerebral cortex cells after MCAO operation.Zhuangtongyin attenuated the accumulation of trivalent iron ions in the brain tissue of mice following MCAO.Additionally,Zhuangtongyin downregulated the expression of TfR1 and DMT1 mRNA(P＜0.001),a transporter associated with cellular iron ion uptake,in the brains of post-MCAO mice.Furthermore,Zhuangtongyin reduced levels of lipid peroxidation product 4-HNE(P＜0.001)and suppressed ACSL4 mRNA expression in brain tissue post-MCAO(P＜0.001).Besides,Zhuangtongyin downregulated the expression of PTGS2 mRNA(P＜0.001),in the brains of post-MCAO mice.Zhuangtongyin increased the expression of nrf2 into the nucleus(P＜0.001),and increased the expression of xCT and Gpx4 in neurons after MCAO(P＜0.001).[Conclusion]Zhuangtongyin can enhance the nerve function and reduce cerebral infarction volume in MCAO/R mice,alleviate the pathological damage of cerebral cortex cells,and modulate the expression of key signaling molecules in the Nrf2-SCL7A11/xCT-Gpx4 pathway.Therefore,it is suggested that the mechanism by which Zhuangtongyin improves MCAO/R injury in mice may involve regulating ferroptosis through the Nrf2-SCL7A11/xCT-GPX4 pathway.

Objective To establish an animal model of dampness-syndrome in mice (single model) and evaluate its characteristics of dampness-syndrome. The above-mentioned mice with dampness syndrome were used to construct mice model of ischemic stroke (double model) and observe the effect of dampness-pathogenic on the outcome of stroke. Methods Healthy C57BL/6J male mice were randomly divided into dampness-syndrome (including sham-surgery group and ischemic stroke group,with 10 mice in each group) and non dampness-syndrome groups (including sham-surgery group and ischemic stroke group,with 10 mice in each group). The dampness-syndrome group was fed with high-fat diet and the non dampness-syndrome group was fed with normal diet for 12 weeks. After the mice model of dampness-syndrome was successfully established,transient middle cerebral artery occlusion/reperfusion (tMCAO/R) surgery was used to replicate an ischemic stroke mice model. Evaluation indicators for dampness-syndrome mice model:the general status including body weight,morphology,posture,activity status,and physical characteristics,the histopathological observation of the aorta (oil red O staining,Masson-trichrome staining) and liver (HE staining,oil red O staining),electron microscopic observation of the tongue tissue (scanning electron microscopy,electron microscopy),blood lipid levels[total cholesterol(TC),triglycerides(TG)]and liver coefficient. Evaluation indicators for ischemic stroke mice model:neurological function score and the cerebral infarction volume ratio. Results Compared with the non dampness-syndrome group,the mice in the dampness-syndrome group showed an increased in body weight,poor hair color,sparse hair,fatigue and laziness,mental atrophy,anorexia and lethargy. It was observed that the aortic lumen was narrowed,the intima was significantly thickened,lipid plaque deposition was increased,and foam cells were visible. A large amount of red lipid droplets appeared in liver cells. There were obvious lipid infiltration and diffuse steatosis. Increased keratosis of the mucosal layer of tongue tissue,the thicker stratum corneum,lipofuscin,and bacteria on the tongue surface were found. Serum TG and TC levels significantly increased(P<0.01),and the liver coefficient significantly decreased (P<0.001). Compared with non dampness-syndrome group (sham-surgery group),neurological function score and the cerebral infarction volume ratio in dampness-syndrome ischemic stroke group obviously increased (P<0.001). Conclusion High-fat feeding for 12 weeks combined with tMCAO/R modeling can successfully establish a mice model with dampness-syndrome ischemic stroke,and the neurological function score and cerebral infarction volume in the dampness-syndrome ischemic stroke group was more severe than that in the non dampness-syndrome ischemic stroke group.

OBJECTIVE：To study the improvement effects of ginsenoside Rb 3 combined with β-asarone on vascular dementia （VD）model mice and its mechanism. METHODS ：ICR mice were randomly divided into model group ，ginsenoside Rb 3 group（10 mg/kg），β-asarone group （10 mg/kg），drug combination group （ginsenoside Rb 3 10 mg/kg+β-asarone 10 mg/kg），positive control group（donepezil hydrochloride 1 mg/kg）and Akt inhibitor group （LY294002，1 mg/kg），and sham operation group was set up ， with 10 mice in each group. Except for sham operation group ，VD model was induced by four vessel occlusion method in other groups. After modeling ，sham operation group and model group were given constant volume of normal saline ，Akt inhibitor group was given relevant medicine intraperitoneally ，and other groups were given relevant medicine intragastrically ，twice a day ，for consecutive 30 d. After last administration ，the learning and memory ability of mice was detected by avoiding darkness test. The contents of 4-hydroxydecenoic acid （4-HNE），8-hydroxydeoxyguanosine （8-OHdG） and reactive oxygen species （ROS） in hippocampus was detected by ELISA. RT-PCR assay was used ， to detect the mRNA expression of Bcl- 2 and Bax inhippocampus. The protein expression of Bcl- 2 in cortex wadetected by immunofluorescence method. Western blotting deng- assay was used to detect the protein expression of Bcl- 2 and mz1@126.com Bax in hippocampus. RESULTS ： Compared with sham operation group ，the incubation period of avoiding darkness xiaoyinlanlp@126.com test in model group was shortened significantly ； and the number of errors was increased significa ntly；4-HNE，8-OHdG and ROS contents ，mRNA and protein expression of Bax were increased significantly ，and mRNA and protein expression of Bcl- 2 was decreased significantly （P＜0.01）. Compared with model group，the incubation period of avoiding darkness test was prolonged significantly in ginsenoside Rb 3 group，β-asarone group ，drug combination group and positive control group ，the number of errors was decreased significantly ；4-HNE，8-OHdG，ROS contents ， mRNA and protein expression of Bax were decreased significantly ，and mRNA and protein expression of Bcl- 2 were increased significantly，especially in drug combination group （P＜0.05 or P＜0.01）. But the incubation period of avoiding darkness test was shortened significantly in Akt inhibitor group ，and the number of errors was increased significantly ；4-HNE，8-OHdG，ROS contents，mRNA and protein expression of Bax were increased significantly ，and mRNA and protein expression of Bcl- 2 were decreased significantly （P＜0.05）. CONCLUSIONS ：Ginsenoside Rb 3 combined with β-asarone has a protective effect on VD model mice ，and the effect was better than that of each compound alone. The mechanism of which may be associated with anti-oxidative stress and anti-apoptosis of hippocampus.

ObjectiveTo investigate the effect of Dingzhi Xiaowan （DZXW） in post-stroke cognitive impairment （PSCI） model mice. MethodsThe cerebral ischemia-reperfusion injury model of mice was established by using the middle cerebral artery occlusion method. Forty C57BL/6 male mice were randomly divided into the sham operation group， model group， low-dose DZXW group （1.43 g·kg^-1）， and high-dose DZXW group （2.56 g·kg^-1）， with 10 mice in each group. Both the sham operation group and the model group were treated with equal amounts of normal saline by gavage， and the above four groups of mice were gavaged once a day for 30 consecutive days. Morris water maze test was used to evaluate the learning memory ability of mice. Serum levels of amyloid precursor protein （APP）， amyloid 42 （Aβ₄₂）， acetylcholinesterase （AChE）， and superoxide dismutase （SOD） were measured by enzyme-linked immunosorbent assay （ELISA）. Deoxyribonucleotide end transferase-mediated nick end labelling （TUNEL） assay was applied to detect the degree of apoptosis in the mouse's hippocampal neurons. Western blot was used to detect the protein expression of phosphoinositol-3 kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor 1-alpha （HIF-1α）， B-cell lymphoma 2 （Bcl-2） homologous structural domain protein （Beclin1）， sequestosome 1 （p62）， microtubule-associated protein light chain 3 （LC3）， Bcl-2， and Bcl-2-associated X protein （Bax） in hippocampal tissue. Prussian blue staining was used to detect iron deposition in hippocampal tissue. Transmission electron microscopy was taken to observe the ultrastructure of the mouse's hippocampal neurons. ResultsCompared with the sham operation group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly increased in the model group （P<0.01）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly decreased （P<0.01）. Compared with the model group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity rate， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly reduced in the DZXW groups （P<0.05）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly higher （P<0.05）. ConclusionDZXW can alleviate cognitive impairment induced by oxidative stress-aggravated hippocampal neuronal damage in PSCI model mice by modulating the PI3K/Akt/mTOR/HIF-1α autophagy signalling pathway.